1) X-ray crystallography shows that upon bis-complexation, dimethylzinc shifts from a linear to tetrahedral geometry, increasing the carbon-zinc bond length and nucleophilicity of the methyl groups.
2) Noyori discovered that (–)-DAIB is a highly selective chiral catalyst for the asymmetric addition of diethyl- and dimethylzinc to aldehydes.
3) The addition rate of dialkylzinc reagents to carbonyl compounds is low at room temperature; addition of TMEDA promotes room temperature addition of diethylzinc to 4-benzoylbenzaldehyde.
The document provides an overview of allenes, including:
1. A brief history of allene synthesis and discoveries dating back to 1828.
2. Details on the structure and properties of allenes compared to alkenes and alkynes based on physical measurements.
3. An overview of common methods for allene synthesis, including organometallic additions and substitutions, carbene and ylide approaches, and rearrangements.
The document summarizes the Wittig olefination reaction, which employs phosphonium ylides to synthesize alkenes. It describes the reaction mechanism, factors that influence stereoselectivity, and methods to generate stabilized and non-stabilized ylides. Examples are provided of industrial and complex synthetic applications of the Wittig reaction. Reviews on the topic and asymmetric variants are also referenced.
The document discusses the synthesis of heterobimetallic NHC ligand based complexes and their catalytic applications. It describes various methods for synthesizing these complexes using triazolylidene and imidazolylidene ligands to link two metal centers. Testing of the complexes showed that combining two metals into a single ligand framework often provides better catalytic performance than using a mixture of homometallic complexes. The binding site of the metals, whether as N^N chelate or NHC, was also found to influence catalytic activity.
Triethylamine-catalyzed reactions of malononitrile, carbon disulfide, and various oxiranes produce functionalized 2-(1,3-oxathiolan-2-ylidene)malononitriles in good yields. The reaction occurs under mild conditions in toluene with triethylamine as base. The products contain a polarized carbon-carbon double bond, as shown by 13C NMR spectroscopy. A range of substituted oxiranes participate in the reaction, affording diverse oxathiolane products in high regioselectivity.
SYNTHESIS AND CHARACTERIZATION OF SOME TRANSITION METAL COMPLEXES WITH A NEW ...EDITOR IJCRCPS
A new monodentate phosphorus yield Ph3P=CHC(O)C6H4-m-Br (L),was synthesized and characterized with elemental analysis as
well as various spectroscopic techniques. The reactions of the title ylide with mercury(II) halides in equimolar ratios using dry
methanol as solvent have yielded [L.HgX2]2 (X= Cl (1), Br (2), I (3)). The reaction of 1 equiv. this ylide with Cd(NO3)2.4H2O in the
same solvent give a polynuclear complex [Cd (L)(NO3)(μ-NO3)]n (4), followed by treatment with 2 equiv. AgNO3 and AgOTf led to
monomeric chelate complexes 5 and 6, respectively. Characterization of the obtained compounds was also performed by
elemental analysis, IR, 1H, 31P and 13C NMR. All DMSO-solved synthesized compounds were subjected to biological evaluation for
their antibacterial against 6 Gram positive and negative bacteria effects by disc diffusion method. Results showed antibacterial
activity for studied metal complexes and suggested their possible application as antibacterial agents.
Keywords: Phosphorus yields, mercury(II) complexes, silver(I) complexes, cadmium(II) complexes, antibacterial activity.
This document summarizes key aspects of palladium-catalyzed cross-coupling reactions, with a focus on the Heck reaction and its mechanisms and applications. The Heck reaction involves the coupling of alkenyl or aryl halides with alkenes, catalyzed by palladium. The mechanism proceeds through oxidative addition, transmetalation, and reductive elimination steps. The document discusses factors that determine regioselectivity and provides examples of the Heck reaction in total syntheses of natural products like dehydrotubifoline, capnellene, and taxol. It also describes domino and intramolecular Heck reactions and summarizes the related Stille coupling reaction.
I. Novel, One-Pot Reactions towards Molecular Alkaline Earth Species, II. Exp...Yuriko Takahashi
Yuriko Takahashi is a PhD candidate at Syracuse University exploring one-pot reactions to synthesize molecular alkaline earth species using benign methods. She has also evaluated how weak interactions influence the thermal properties and volatility of compounds for metal organic chemical vapor deposition. Her research involves inert gas techniques, NMR studies, crystallography, thermogravimetric analysis, and ligand synthesis. She finds that redox transmetallation using BiPh3 provides an environmentally friendly alternative to organomercury compounds for alkaline earth synthesis, with reaction rates significantly faster than direct metallation. Exploring weak intermolecular interactions may help determine structure-property relationships for improving volatility in MOCVD applications.
The Noyori asymmetric hydrogenation reaction uses a chiral Ru catalyst derived from (R)-BINAP to reduce prochiral ketones to chiral secondary alcohols with high enantioselectivity. Key features include:
1) The Ru-BINAP catalyst is generated in situ from commercially available BINAP and Ru precursors. Reactions proceed under mild conditions like 4-100 atm H2, 23-100°C.
2) A variety of ketone substrates are reduced with high yields (up to 99%) and enantioselectivities (up to >99% ee). Dynamic kinetic resolutions allow up to 100% yield.
3) The stereochemistry of the product is determined
The document provides an overview of allenes, including:
1. A brief history of allene synthesis and discoveries dating back to 1828.
2. Details on the structure and properties of allenes compared to alkenes and alkynes based on physical measurements.
3. An overview of common methods for allene synthesis, including organometallic additions and substitutions, carbene and ylide approaches, and rearrangements.
The document summarizes the Wittig olefination reaction, which employs phosphonium ylides to synthesize alkenes. It describes the reaction mechanism, factors that influence stereoselectivity, and methods to generate stabilized and non-stabilized ylides. Examples are provided of industrial and complex synthetic applications of the Wittig reaction. Reviews on the topic and asymmetric variants are also referenced.
The document discusses the synthesis of heterobimetallic NHC ligand based complexes and their catalytic applications. It describes various methods for synthesizing these complexes using triazolylidene and imidazolylidene ligands to link two metal centers. Testing of the complexes showed that combining two metals into a single ligand framework often provides better catalytic performance than using a mixture of homometallic complexes. The binding site of the metals, whether as N^N chelate or NHC, was also found to influence catalytic activity.
Triethylamine-catalyzed reactions of malononitrile, carbon disulfide, and various oxiranes produce functionalized 2-(1,3-oxathiolan-2-ylidene)malononitriles in good yields. The reaction occurs under mild conditions in toluene with triethylamine as base. The products contain a polarized carbon-carbon double bond, as shown by 13C NMR spectroscopy. A range of substituted oxiranes participate in the reaction, affording diverse oxathiolane products in high regioselectivity.
SYNTHESIS AND CHARACTERIZATION OF SOME TRANSITION METAL COMPLEXES WITH A NEW ...EDITOR IJCRCPS
A new monodentate phosphorus yield Ph3P=CHC(O)C6H4-m-Br (L),was synthesized and characterized with elemental analysis as
well as various spectroscopic techniques. The reactions of the title ylide with mercury(II) halides in equimolar ratios using dry
methanol as solvent have yielded [L.HgX2]2 (X= Cl (1), Br (2), I (3)). The reaction of 1 equiv. this ylide with Cd(NO3)2.4H2O in the
same solvent give a polynuclear complex [Cd (L)(NO3)(μ-NO3)]n (4), followed by treatment with 2 equiv. AgNO3 and AgOTf led to
monomeric chelate complexes 5 and 6, respectively. Characterization of the obtained compounds was also performed by
elemental analysis, IR, 1H, 31P and 13C NMR. All DMSO-solved synthesized compounds were subjected to biological evaluation for
their antibacterial against 6 Gram positive and negative bacteria effects by disc diffusion method. Results showed antibacterial
activity for studied metal complexes and suggested their possible application as antibacterial agents.
Keywords: Phosphorus yields, mercury(II) complexes, silver(I) complexes, cadmium(II) complexes, antibacterial activity.
This document summarizes key aspects of palladium-catalyzed cross-coupling reactions, with a focus on the Heck reaction and its mechanisms and applications. The Heck reaction involves the coupling of alkenyl or aryl halides with alkenes, catalyzed by palladium. The mechanism proceeds through oxidative addition, transmetalation, and reductive elimination steps. The document discusses factors that determine regioselectivity and provides examples of the Heck reaction in total syntheses of natural products like dehydrotubifoline, capnellene, and taxol. It also describes domino and intramolecular Heck reactions and summarizes the related Stille coupling reaction.
I. Novel, One-Pot Reactions towards Molecular Alkaline Earth Species, II. Exp...Yuriko Takahashi
Yuriko Takahashi is a PhD candidate at Syracuse University exploring one-pot reactions to synthesize molecular alkaline earth species using benign methods. She has also evaluated how weak interactions influence the thermal properties and volatility of compounds for metal organic chemical vapor deposition. Her research involves inert gas techniques, NMR studies, crystallography, thermogravimetric analysis, and ligand synthesis. She finds that redox transmetallation using BiPh3 provides an environmentally friendly alternative to organomercury compounds for alkaline earth synthesis, with reaction rates significantly faster than direct metallation. Exploring weak intermolecular interactions may help determine structure-property relationships for improving volatility in MOCVD applications.
The Noyori asymmetric hydrogenation reaction uses a chiral Ru catalyst derived from (R)-BINAP to reduce prochiral ketones to chiral secondary alcohols with high enantioselectivity. Key features include:
1) The Ru-BINAP catalyst is generated in situ from commercially available BINAP and Ru precursors. Reactions proceed under mild conditions like 4-100 atm H2, 23-100°C.
2) A variety of ketone substrates are reduced with high yields (up to 99%) and enantioselectivities (up to >99% ee). Dynamic kinetic resolutions allow up to 100% yield.
3) The stereochemistry of the product is determined
The document describes a method for synthesizing aryl hydrazides from aryl halides using a Mitsunobo reagent system. Key points:
- Aryl iodides and bromides react with triphenylphosphine and dialkyl azodicarboxylates in the presence of copper(I) iodide catalyst to form the corresponding aryl hydrazides in good yields.
- For aryl iodides, the optimized conditions are copper(I) iodide catalyst at room temperature in THF. For aryl bromides, higher temperatures (60-75°C) in acetonitrile with copper(I) iodide and 1,10-phenanthroline ligand
Hirschfield_Ilan Undergraduate Thesis Research Summary.pptxIlanHirschfield
Summary of my undergraduate honors thesis chemical research I conducted. In this presentation, I give background to the significance of this research, a brief review of previous research done in the field, report the findings of this study, deliver several conclusions of the study, and propose further work that can be conducted in this research area.
I’m a Responsible Scientist skilled in small molecule chiral and achiral molecule development enthusiastically looking for an opportunity to use my background for API (Active Pharmaceutical Ingredient) development by leveraging demonstrated strategies synthetic route development, cost-reduction and project management while interacting with cross-functional teams to contribute high-quality outcome for Pharmaceuticals. I am highly looking forward to discuss further opportunities with you. Please don't hesitate to contact me > ramesh.yella@aol.com
Rh(I)-catalyzed Aldol-type Reaction of Organonitriles under Mild Conditions: ...Stephan Irle
Rh(I)-catalyzed aldol-type reactions of organonitriles were investigated using theoretical and experimental methods. Quantum chemistry calculations revealed that the monomeric form of the Rh catalyst is preferred over the dimeric form. The reaction is proposed to proceed via the Rh(CH3CN)2 monomer, which forms a reactive intermediate complex with benzaldehyde that overcomes a reaction barrier of around 30 kcal/mol. Accurate treatment of solvent effects, such as with MP2-RISM calculations, is important for determining the reaction mechanism and barriers.
The document reports on the crystal structure of bis{2-[4-(methylsulfanyl)phenyl]-1H-benzimidazol-3-ium} tetrabromidocuprate(II) dihydrate. The asymmetric unit contains two organic cations, one copper(II) anion, and two water molecules. The cations are arranged in a head-to-tail fashion and stacked along [100]. The crystal structure is stabilized by hydrogen bonds between the organic cations, water molecules, and bromine anions.
Organocatalytic enantioselective conjugate addition of aldehydes to maleimidesDrMAdamSayah
1) The document describes an organocatalytic method for the highly enantioselective conjugate addition of aldehydes to maleimides.
2) Using a protected diarylprolinol catalyst, a variety of aldehydes were added to maleimides with 97-99% enantiomeric excess.
3) X-ray crystallography determined the absolute configuration and a transition state model is proposed to explain the stereochemical outcome.
Applications of Phosphine ligands in Pd and Ru-Catalyzed ReactionsGowrisankar Saravanan
1. The document summarizes research on the development and application of new phosphine and phosphomide ligands in metal-catalyzed reactions.
2. Key findings include using modified pyrazole-based phosphine ligands for efficient C-O cross-coupling reactions and Pd-catalyzed oxidative esterification to form cross and self esters.
3. A new class of phosphomide-based phosphine ligands was also prepared and successfully applied to ruthenium-catalyzed hydrogenation of sodium bicarbonate.
A kinetic study is reported for the homologation of methanol to give ethanol. Cobalt carbonyl and iodine or cobalt iodide were used as catalyst systems with tri-n-butylphosphine as ligand. The reaction was investigated in 1,4-dioxane in a batch unit at (CO + H2) pressures between 3 and 15 MPa, with H2/CO ratios in the range of 0.33
to 3. The temperature was varied over the range of 150 to 210°C. The reaction rate was found to be first order with respect to methanol and cobalt concentrations and CO partial pressure. A rate expression is derived. A reaction mechanism is proposed in which the rate-determining step is suggested to be the reaction of methanol with a CO-rich cobalt complex existing in low concentration with regard to cobalt used.
This document summarizes Daniel Tan Teoh Chuan's MSc research on the synthesis and antibacterial evaluation of juglone derivatives. The objectives were to synthesize juglone derivatives from juglone and non-juglone starting materials, characterize the compounds, and evaluate their antibacterial activities. Key reactions included Diels-Alder and Friedel-Crafts acylation. Derivatives were purified and characterized using various analytical techniques. The antibacterial assay found several derivatives had similar or better activity than juglone against several bacterial strains.
Synthesis of new 2 h pyrano[3,2-h]quinolines with potential biological activityAlexander Decker
The document summarizes the synthesis of new 2H-pyrano[3,2-h]quinoline derivatives with potential biological activity. 5-halo-8-hydroxyquinoline-7-carboxaldehyde reacted with diethyl malonate to produce ethyl 6-halo-2-oxo-2H-pyrano[3,2-h]quinoline-3-carboxylates, which underwent further reactions to form derivatives containing pyrane, pyrazole, indole and oxadiazino[5,6-b]indole moieties. The biological screening showed some of the pyrano[3,2-h]quinoline derivatives have excellent antibacterial and ant
METALLO - BIOACTIVE COMPOUNDS AS POTENTIAL NOVEL ANTICANCER THERAPYijac123
Mono and bi-organometallic complexes of Cu(II), Ni(II), Mn(II), Zn(II) and Ag(I) complexes with
oxaloamide ligand has much potential as therapeutic and diagnostic agents. The ligand allows the
thermodynamic and kinetic reactivity of the metal ion to be controlled and also provide a scaffold for
functionalization. Specific examples involving the design of metal complexes as anticancer agents are
discussed. These complexes have been synthesized and characterized by (1H-NMR, mass, IR, UV-VIS,
ESR) spectra, magnetic moments and conductance measurements, elemental and thermal analyses. Molar
conductances in DMF solution indicates that, the complexes are non-electrolytes. The ESR spectra of solid
Cu(II) complexes (2-5) show an axial type indicating a d(X2-y2) ground state with a significant covalent
bond character. However, Mn(II) complex(9), shows an isotropic type indicating an octahedral geometry.
Cytotoxic evolution IC50 of the ligand and its complexes have been carried out. Cu(II) Complexes show
enhanced activity in comparison to the parent ligand or standard drug. Copper is enriched in various
human cancer tissues and is a co-factor essential for tumor angiogenesis processes. However, the use of
copper binding ligand to target tumor, copper could provide a novel strategy for cancer selective
treatment.
Unimolecular decompositions of acyclic ethers through a pericyclic mechanism, i.e., alcohol elimination, have been shown to play a crucial role in the high-temperature combustion of these compounds. The production of new fuels derived from biomass has led to a renewed interest into the combustion chemistry of ethers. A large fraction of ethers produced as potential biofuels features a cyclic structure. The pericyclic reactions in these cyclic structures, with or without a lateral alkyl group, remains unknown. In this work, we performed a systematic theoretical study on the pericyclic reactions in acyclic and cyclic ethers. Envisaged concerted reactions includes the classical alcohol formation and a H2 eliminations that was recently shown to play a non negligible role in the thermal decomposition of tetrahydrofuran (Verdicchio et al., 2015). Theoretical calculations performed in this work demonstrated that H2 elimination in acyclic ethers is negligible. In the case of cyclic ethers (tetrahydrofuran and tetrahydropyran), the branching ratio of the unimolecular pericyclic reactions strongly depends on the presence of a lateral alkyl group bonded to the carbon atom in position 2. If an alkyl group is present, the alcohol formation is favored through an exo 4-center rearrangement, that we newly defined in this work. If no lateral alkyl group is available in position 2, endo alcohol formation and H2 eliminations are equivalently important. Reaction rate rules were established to include pericyclic decomposition reactions in detailed chemical kinetic models of ether combustion.
For more information: Proceedings of the Combustion Institute 2017, 36 (1), 569-576
https://www.sciencedirect.com/science/article/pii/S1540748916302917
Synthesis, Characterization, and Antibacterial Activity of Some Novel 5-Chlor...IJERA Editor
The development of potential antibacterial requires the synthesis of a new series of 5- Chloroisatin derivatives incorporating various aromatic aldehydes in the case 1,3-Dipolar Cycloaddition including Nitrile oxide, as well as the cycloaddition Alcyne-Azide Catalytic with Copper. The charcterization of the structure of the synthesized compounds was confirmed by means of their IR, 1H-NMR and 13C-NMR spectral data. In addition, the antibacterial properties in vitro were tested against certain microorganisms using the disk diffusion technique. A majority of compounds show better activity against several of the microorganisms.
This document summarizes the synthesis of tris(4-((E)-2-nitro-3-(phenylamino)prop-1-enyl)phenyl)amine from a Baylis–Hillman adduct. Specifically, it details the reaction of tris(4-((E)-3-bromo-2-nitroprop-1-enyl)phenyl)amine with aniline to yield the target compound in 95% yield. The synthesis demonstrates the utility of bromo derivatives of Baylis–Hillman adducts as intermediates for generating novel trisubstituted triallylamines. Characterization of the product by NMR spectroscopy is also discussed.
N-alkylation methods, Characterization and Evaluation of antibacterial activi...IJERA Editor
A series of new 5-Chloroisatin derivates have been synthesized by the method of N-alkylation at room temperature, in the presence of a base and a catalyst with good yields. The chemical structures of these compounds were confirmed by NMR (1H &13C), these new compounds obtained were evaluated for their antibacterial activity. The final results revealed that the majority of the compounds exhibited good antimicrobial activity against various organisms
Polymer-Supported N-Tritylaziridinyl(diphenyl)methanol as an Effective Cataly...Peter ten Holte
This document describes the use of a polymer-supported N-tritylaziridinyl(diphenyl)methanol catalyst (2) for the enantioselective addition of diethylzinc to various aldehydes. Catalyst 2 was synthesized by attaching an aziridinyl alcohol to a polymer support. It catalyzed the addition of diethylzinc to aromatic and aliphatic aldehydes with high yields (up to 92%) and enantioselectivities (up to 97% ee). The catalyst could be recycled through multiple reaction cycles with retention of high enantioselectivity (95-96% ee).
Polymer-Supported N-Tritylaziridinyl(diphenyl)methanol as an Effective Cataly...Peter ten Holte
This document describes the use of a polymer-supported N-tritylaziridinyl(diphenyl)methanol catalyst (2) for the enantioselective addition of diethylzinc to various aldehydes. Catalyst 2 was synthesized by attaching an aziridinylmethanol to a polymer-bound trityl chloride. It catalyzed the addition of diethylzinc to aromatic and aliphatic aldehydes with high yields (up to 92%) and enantioselectivities (up to 97% ee). The catalyst could be recycled through multiple reaction cycles with retention of high enantioselectivity (95-96% ee).
A copper-catalyzed synthesis of N-sulfonylamidines is reported via a three-component coupling of sulfonyl azides, terminal alkynes, and trialkylamines. The reaction involves the formation of a ketenimine intermediate through 1,3-dipolar cycloaddition of the sulfonyl azide and copper acetylide, which is then trapped by the trialkylamine to form the N-sulfonylamidine product. The method provides a practical route for synthesizing functionalized N-sulfonylamidines in good yields under mild conditions.
An Efficient Synthetic Approach Towards 4-Cyano-3-(Methylthio)-5-Oxo-2H-Pyraz...inventionjournals
ABSTRACT: Synthesis of novel heterocyclic 4-cyano -3-(methylthio)-5-oxo-2H-pyrazole-1(5H)- carbothioamide (3) was prepared by condensing ethyl-2-cyano-3,3-bis (methylthio)acrylate (1) with thiosemicarbazide (2) in DMF and catalytic amount of potassium carbonate. Compound (3) has methylthio group at third position, which is replaced by different nucleophiles such as substituted anilines| phenols| hetryl amines| compounds containing active methylene group to afford 3-substituted derivatives of compound (3). All the newly synthesized compounds were screened for their antimicrobial activity.
A ruthenium trinuclear polyazine complex was synthesized and subsequently immobilized through
complexation to a graphene oxide support containing phenanthroline ligands (GO-phen). The developed
photocatalyst was used for the photocatalytic reduction of CO2 to methanol, using a 20 watt white cold
LED flood light, in a dimethyl formamide–water mixture containing triethylamine as a reductive
quencher. After 48 h illumination, the yield of methanol was found to be 3977.57 5.60 mmol gcat
1.
The developed photocatalyst exhibited a higher photocatalytic activity than graphene oxide, which
provided a yield of 2201.40 8.76 mmol gcat
1. After the reaction, the catalyst was easily recovered and
reused for four subsequent runs without a significant loss of catalytic activity and no leaching of the
metal/ligand was detected during the reaction.
The document discusses various aspects of marketing mix and pricing strategies. It explains the 4Ps of marketing mix - product, price, place and promotion. It also discusses different pricing approaches including cost-based pricing, value-based pricing and competition-based pricing. The document provides examples and details on factors to consider when setting prices, product pricing strategies, and pricing of product mixes.
Cost and management accounting provides managers with detailed cost information to control operations and plan for the future. Cost accounting information is used for financial accounting and by managers for decision making. Management accounting provides economic and financial information for internal users. Cost concepts like cost objects, cost pools, and cost drivers are introduced. Costs are classified by elements, functions, traceability, behavior, and controllability. Product costs include direct materials, direct labor, and manufacturing overhead and become inventory until goods are sold. Period costs are expenses of the current period. Job order costing and process costing are introduced as costing systems. Just-in-time processing, activity-based costing, cost-volume-profit analysis, contribution margin,
The document describes a method for synthesizing aryl hydrazides from aryl halides using a Mitsunobo reagent system. Key points:
- Aryl iodides and bromides react with triphenylphosphine and dialkyl azodicarboxylates in the presence of copper(I) iodide catalyst to form the corresponding aryl hydrazides in good yields.
- For aryl iodides, the optimized conditions are copper(I) iodide catalyst at room temperature in THF. For aryl bromides, higher temperatures (60-75°C) in acetonitrile with copper(I) iodide and 1,10-phenanthroline ligand
Hirschfield_Ilan Undergraduate Thesis Research Summary.pptxIlanHirschfield
Summary of my undergraduate honors thesis chemical research I conducted. In this presentation, I give background to the significance of this research, a brief review of previous research done in the field, report the findings of this study, deliver several conclusions of the study, and propose further work that can be conducted in this research area.
I’m a Responsible Scientist skilled in small molecule chiral and achiral molecule development enthusiastically looking for an opportunity to use my background for API (Active Pharmaceutical Ingredient) development by leveraging demonstrated strategies synthetic route development, cost-reduction and project management while interacting with cross-functional teams to contribute high-quality outcome for Pharmaceuticals. I am highly looking forward to discuss further opportunities with you. Please don't hesitate to contact me > ramesh.yella@aol.com
Rh(I)-catalyzed Aldol-type Reaction of Organonitriles under Mild Conditions: ...Stephan Irle
Rh(I)-catalyzed aldol-type reactions of organonitriles were investigated using theoretical and experimental methods. Quantum chemistry calculations revealed that the monomeric form of the Rh catalyst is preferred over the dimeric form. The reaction is proposed to proceed via the Rh(CH3CN)2 monomer, which forms a reactive intermediate complex with benzaldehyde that overcomes a reaction barrier of around 30 kcal/mol. Accurate treatment of solvent effects, such as with MP2-RISM calculations, is important for determining the reaction mechanism and barriers.
The document reports on the crystal structure of bis{2-[4-(methylsulfanyl)phenyl]-1H-benzimidazol-3-ium} tetrabromidocuprate(II) dihydrate. The asymmetric unit contains two organic cations, one copper(II) anion, and two water molecules. The cations are arranged in a head-to-tail fashion and stacked along [100]. The crystal structure is stabilized by hydrogen bonds between the organic cations, water molecules, and bromine anions.
Organocatalytic enantioselective conjugate addition of aldehydes to maleimidesDrMAdamSayah
1) The document describes an organocatalytic method for the highly enantioselective conjugate addition of aldehydes to maleimides.
2) Using a protected diarylprolinol catalyst, a variety of aldehydes were added to maleimides with 97-99% enantiomeric excess.
3) X-ray crystallography determined the absolute configuration and a transition state model is proposed to explain the stereochemical outcome.
Applications of Phosphine ligands in Pd and Ru-Catalyzed ReactionsGowrisankar Saravanan
1. The document summarizes research on the development and application of new phosphine and phosphomide ligands in metal-catalyzed reactions.
2. Key findings include using modified pyrazole-based phosphine ligands for efficient C-O cross-coupling reactions and Pd-catalyzed oxidative esterification to form cross and self esters.
3. A new class of phosphomide-based phosphine ligands was also prepared and successfully applied to ruthenium-catalyzed hydrogenation of sodium bicarbonate.
A kinetic study is reported for the homologation of methanol to give ethanol. Cobalt carbonyl and iodine or cobalt iodide were used as catalyst systems with tri-n-butylphosphine as ligand. The reaction was investigated in 1,4-dioxane in a batch unit at (CO + H2) pressures between 3 and 15 MPa, with H2/CO ratios in the range of 0.33
to 3. The temperature was varied over the range of 150 to 210°C. The reaction rate was found to be first order with respect to methanol and cobalt concentrations and CO partial pressure. A rate expression is derived. A reaction mechanism is proposed in which the rate-determining step is suggested to be the reaction of methanol with a CO-rich cobalt complex existing in low concentration with regard to cobalt used.
This document summarizes Daniel Tan Teoh Chuan's MSc research on the synthesis and antibacterial evaluation of juglone derivatives. The objectives were to synthesize juglone derivatives from juglone and non-juglone starting materials, characterize the compounds, and evaluate their antibacterial activities. Key reactions included Diels-Alder and Friedel-Crafts acylation. Derivatives were purified and characterized using various analytical techniques. The antibacterial assay found several derivatives had similar or better activity than juglone against several bacterial strains.
Synthesis of new 2 h pyrano[3,2-h]quinolines with potential biological activityAlexander Decker
The document summarizes the synthesis of new 2H-pyrano[3,2-h]quinoline derivatives with potential biological activity. 5-halo-8-hydroxyquinoline-7-carboxaldehyde reacted with diethyl malonate to produce ethyl 6-halo-2-oxo-2H-pyrano[3,2-h]quinoline-3-carboxylates, which underwent further reactions to form derivatives containing pyrane, pyrazole, indole and oxadiazino[5,6-b]indole moieties. The biological screening showed some of the pyrano[3,2-h]quinoline derivatives have excellent antibacterial and ant
METALLO - BIOACTIVE COMPOUNDS AS POTENTIAL NOVEL ANTICANCER THERAPYijac123
Mono and bi-organometallic complexes of Cu(II), Ni(II), Mn(II), Zn(II) and Ag(I) complexes with
oxaloamide ligand has much potential as therapeutic and diagnostic agents. The ligand allows the
thermodynamic and kinetic reactivity of the metal ion to be controlled and also provide a scaffold for
functionalization. Specific examples involving the design of metal complexes as anticancer agents are
discussed. These complexes have been synthesized and characterized by (1H-NMR, mass, IR, UV-VIS,
ESR) spectra, magnetic moments and conductance measurements, elemental and thermal analyses. Molar
conductances in DMF solution indicates that, the complexes are non-electrolytes. The ESR spectra of solid
Cu(II) complexes (2-5) show an axial type indicating a d(X2-y2) ground state with a significant covalent
bond character. However, Mn(II) complex(9), shows an isotropic type indicating an octahedral geometry.
Cytotoxic evolution IC50 of the ligand and its complexes have been carried out. Cu(II) Complexes show
enhanced activity in comparison to the parent ligand or standard drug. Copper is enriched in various
human cancer tissues and is a co-factor essential for tumor angiogenesis processes. However, the use of
copper binding ligand to target tumor, copper could provide a novel strategy for cancer selective
treatment.
Unimolecular decompositions of acyclic ethers through a pericyclic mechanism, i.e., alcohol elimination, have been shown to play a crucial role in the high-temperature combustion of these compounds. The production of new fuels derived from biomass has led to a renewed interest into the combustion chemistry of ethers. A large fraction of ethers produced as potential biofuels features a cyclic structure. The pericyclic reactions in these cyclic structures, with or without a lateral alkyl group, remains unknown. In this work, we performed a systematic theoretical study on the pericyclic reactions in acyclic and cyclic ethers. Envisaged concerted reactions includes the classical alcohol formation and a H2 eliminations that was recently shown to play a non negligible role in the thermal decomposition of tetrahydrofuran (Verdicchio et al., 2015). Theoretical calculations performed in this work demonstrated that H2 elimination in acyclic ethers is negligible. In the case of cyclic ethers (tetrahydrofuran and tetrahydropyran), the branching ratio of the unimolecular pericyclic reactions strongly depends on the presence of a lateral alkyl group bonded to the carbon atom in position 2. If an alkyl group is present, the alcohol formation is favored through an exo 4-center rearrangement, that we newly defined in this work. If no lateral alkyl group is available in position 2, endo alcohol formation and H2 eliminations are equivalently important. Reaction rate rules were established to include pericyclic decomposition reactions in detailed chemical kinetic models of ether combustion.
For more information: Proceedings of the Combustion Institute 2017, 36 (1), 569-576
https://www.sciencedirect.com/science/article/pii/S1540748916302917
Synthesis, Characterization, and Antibacterial Activity of Some Novel 5-Chlor...IJERA Editor
The development of potential antibacterial requires the synthesis of a new series of 5- Chloroisatin derivatives incorporating various aromatic aldehydes in the case 1,3-Dipolar Cycloaddition including Nitrile oxide, as well as the cycloaddition Alcyne-Azide Catalytic with Copper. The charcterization of the structure of the synthesized compounds was confirmed by means of their IR, 1H-NMR and 13C-NMR spectral data. In addition, the antibacterial properties in vitro were tested against certain microorganisms using the disk diffusion technique. A majority of compounds show better activity against several of the microorganisms.
This document summarizes the synthesis of tris(4-((E)-2-nitro-3-(phenylamino)prop-1-enyl)phenyl)amine from a Baylis–Hillman adduct. Specifically, it details the reaction of tris(4-((E)-3-bromo-2-nitroprop-1-enyl)phenyl)amine with aniline to yield the target compound in 95% yield. The synthesis demonstrates the utility of bromo derivatives of Baylis–Hillman adducts as intermediates for generating novel trisubstituted triallylamines. Characterization of the product by NMR spectroscopy is also discussed.
N-alkylation methods, Characterization and Evaluation of antibacterial activi...IJERA Editor
A series of new 5-Chloroisatin derivates have been synthesized by the method of N-alkylation at room temperature, in the presence of a base and a catalyst with good yields. The chemical structures of these compounds were confirmed by NMR (1H &13C), these new compounds obtained were evaluated for their antibacterial activity. The final results revealed that the majority of the compounds exhibited good antimicrobial activity against various organisms
Polymer-Supported N-Tritylaziridinyl(diphenyl)methanol as an Effective Cataly...Peter ten Holte
This document describes the use of a polymer-supported N-tritylaziridinyl(diphenyl)methanol catalyst (2) for the enantioselective addition of diethylzinc to various aldehydes. Catalyst 2 was synthesized by attaching an aziridinyl alcohol to a polymer support. It catalyzed the addition of diethylzinc to aromatic and aliphatic aldehydes with high yields (up to 92%) and enantioselectivities (up to 97% ee). The catalyst could be recycled through multiple reaction cycles with retention of high enantioselectivity (95-96% ee).
Polymer-Supported N-Tritylaziridinyl(diphenyl)methanol as an Effective Cataly...Peter ten Holte
This document describes the use of a polymer-supported N-tritylaziridinyl(diphenyl)methanol catalyst (2) for the enantioselective addition of diethylzinc to various aldehydes. Catalyst 2 was synthesized by attaching an aziridinylmethanol to a polymer-bound trityl chloride. It catalyzed the addition of diethylzinc to aromatic and aliphatic aldehydes with high yields (up to 92%) and enantioselectivities (up to 97% ee). The catalyst could be recycled through multiple reaction cycles with retention of high enantioselectivity (95-96% ee).
A copper-catalyzed synthesis of N-sulfonylamidines is reported via a three-component coupling of sulfonyl azides, terminal alkynes, and trialkylamines. The reaction involves the formation of a ketenimine intermediate through 1,3-dipolar cycloaddition of the sulfonyl azide and copper acetylide, which is then trapped by the trialkylamine to form the N-sulfonylamidine product. The method provides a practical route for synthesizing functionalized N-sulfonylamidines in good yields under mild conditions.
An Efficient Synthetic Approach Towards 4-Cyano-3-(Methylthio)-5-Oxo-2H-Pyraz...inventionjournals
ABSTRACT: Synthesis of novel heterocyclic 4-cyano -3-(methylthio)-5-oxo-2H-pyrazole-1(5H)- carbothioamide (3) was prepared by condensing ethyl-2-cyano-3,3-bis (methylthio)acrylate (1) with thiosemicarbazide (2) in DMF and catalytic amount of potassium carbonate. Compound (3) has methylthio group at third position, which is replaced by different nucleophiles such as substituted anilines| phenols| hetryl amines| compounds containing active methylene group to afford 3-substituted derivatives of compound (3). All the newly synthesized compounds were screened for their antimicrobial activity.
A ruthenium trinuclear polyazine complex was synthesized and subsequently immobilized through
complexation to a graphene oxide support containing phenanthroline ligands (GO-phen). The developed
photocatalyst was used for the photocatalytic reduction of CO2 to methanol, using a 20 watt white cold
LED flood light, in a dimethyl formamide–water mixture containing triethylamine as a reductive
quencher. After 48 h illumination, the yield of methanol was found to be 3977.57 5.60 mmol gcat
1.
The developed photocatalyst exhibited a higher photocatalytic activity than graphene oxide, which
provided a yield of 2201.40 8.76 mmol gcat
1. After the reaction, the catalyst was easily recovered and
reused for four subsequent runs without a significant loss of catalytic activity and no leaching of the
metal/ligand was detected during the reaction.
The document discusses various aspects of marketing mix and pricing strategies. It explains the 4Ps of marketing mix - product, price, place and promotion. It also discusses different pricing approaches including cost-based pricing, value-based pricing and competition-based pricing. The document provides examples and details on factors to consider when setting prices, product pricing strategies, and pricing of product mixes.
Cost and management accounting provides managers with detailed cost information to control operations and plan for the future. Cost accounting information is used for financial accounting and by managers for decision making. Management accounting provides economic and financial information for internal users. Cost concepts like cost objects, cost pools, and cost drivers are introduced. Costs are classified by elements, functions, traceability, behavior, and controllability. Product costs include direct materials, direct labor, and manufacturing overhead and become inventory until goods are sold. Period costs are expenses of the current period. Job order costing and process costing are introduced as costing systems. Just-in-time processing, activity-based costing, cost-volume-profit analysis, contribution margin,
This document provides an overview of an accounting and finance course for managers. It has three independent parts: financial accounting and reporting, management and cost accounting, and financial management. The course contents include introductions to accounting processes, management accounting, and financial management. It discusses accounting as an information system and decision making tool for both internal and external users. The key differences between financial and management accounting are explained, with financial accounting following GAAP and providing information to external users, while management accounting focuses on internal reporting and decision making needs.
This document discusses marketing research and its process. It defines marketing research as the systematic design, collection, analysis and reporting of data relevant to a specific marketing situation. The marketing research process involves 6 steps: 1) define the problem, 2) develop a research plan, 3) collect information, 4) analyze the information, 5) present findings, and 6) make a decision. It describes various data sources, research approaches, research instruments including different types of questions, and sampling plans that can be used in marketing research.
The document provides an overview of strategic marketing planning concepts. It discusses strategic planning processes including defining an organizational mission, setting objectives, and designing business portfolios. Methods for analyzing business portfolios such as the BCG matrix and GE planning grid are also outlined. The document then covers growth strategies like market penetration and product development as well as competitive strategies like market leadership. Finally, it describes key components of a marketing plan such as situation analysis, goals and objectives, marketing strategies, implementation, and evaluation.
Industrial development involves manufacturing and industrial processes that drive economic growth and development. The document discusses the history and key aspects of industrialization, including its role in transforming economies from agricultural to manufacturing-based. Industrialization is characterized by increasing mechanization, division of labor, and use of technology. It provides benefits like higher incomes, employment, productivity, and living standards. Countries developed different models of industrialization, and it remains an important process for economic development.
Phytotoxins are toxic substances produced by plants, microorganisms, or chemical reactions that are poisonous to plant growth. They serve defensive functions for plants and include alkaloids, terpenes, and phenolics. Phytotoxins play important roles in medicine in fields like forensic toxicology and pharmacology. The castor oil plant produces several toxic compounds in its leaves and seeds like ricinoleic acid and the lethal toxin ricin. Ingestion of castor beans can cause severe gastrointestinal effects and be fatal. Symptoms develop within hours of ingestion.
For [Cr(H2O)6]Cl3:
- Primary valence of Cr is 3+
- Secondary valence is satisfied by 6 ligands (H2O)
- So secondary valence is 6
For [Co(NH3)5Cl]Cl2:
- Primary valence of Co is 2+
- Secondary valence is satisfied by 5 ligands (NH3) and 1 ligand (Cl)
- So secondary valence is 6
This document discusses designing remote connectivity for employees who work offsite. It describes different types of remote workers and their need for enterprise network connectivity. The enterprise edge, where the enterprise network connects to external networks, requires special design considerations for bandwidth costs, quality of service, security, and remote access. The document also discusses integrating remote sites using various wide area network technologies, virtual private networks, and ensuring redundancy through backup links.
The document discusses IP addressing hierarchy and route summarization. It explains that hierarchical IP addressing and route summarization reduce routing overhead by allowing more specific routes to be aggregated into less specific summary routes. This hierarchical structure mirrors that used in telephone numbering. The document also discusses factors to consider when designing an IP addressing plan such as using fixed-length versus variable-length subnet masks and the impacts of a poorly designed addressing scheme.
This document discusses the basics of network design and the benefits of hierarchical network design. It introduces network design goals of scalability, availability, security and manageability. A hierarchical network design groups devices into multiple layered networks of core, distribution and access layers. This approach allows local traffic to remain local, improves traffic filtering and control, and prevents network degradation as more devices are added.
The document discusses different types of isomers including constitutional isomers, stereoisomers, geometric isomers (cis and trans), enantiomers, and diastereomers. It provides examples of each type of isomer and methods for distinguishing between them, such as assigning R/S configurations using Cahn-Ingold-Prelog rules and distinguishing cis and trans isomers based on whether substituents are on the same or opposite sides. Key topics covered include chiral centers, optical activity, specific rotation, meso compounds, racemic mixtures, and resolution of enantiomers.
This document reviews the effects of soil and water conservation practices on soil loss and nutrient loss in Ethiopia. It discusses how conservation practices like terracing, check dams, crop rotation, and mulching can help minimize erosion and improve soil fertility. Studies have found that these practices significantly reduce soil loss compared to untreated land, helping to rehabilitate degraded land. Soil properties like organic matter, nitrogen, and cation exchange capacity are also improved. Overall, the document concludes that soil and water conservation is important for sustainable agriculture and the environment in Ethiopia.
This 3-sentence document summary provides the high-level information:
This project proposal examines factors affecting the quality of primary education for poor children in the town of Wolaita Sodo. It aims to identify challenges to delivering quality primary education to underprivileged children in the area. Recommendations will be made to improve education for poor students and help more children in the community to complete primary school.
Gas-liquid chromatography is an effective method for separating, identifying, and quantifying complex mixtures. It has high separation efficiency and reproducibility compared to other chromatography methods. Gas-liquid chromatography also offers high sensitivity, universal detection techniques, and columns that can be used for long periods of time. However, reference standards are needed to quantify very small amounts of a substance.
This document summarizes key information about organozinc compounds:
1. Organozinc compounds contain carbon-zinc bonds and were among the first organometallic compounds synthesized.
2. They are less reactive than other organometallic reagents like Grignard and organolithium compounds.
3. Organozinc compounds react through reactions like the Reformatsky reaction, Simmons-Smith reaction, Negishi coupling and Fukuyama coupling to form carbon-carbon bonds. They can also be used to introduce functional groups.
This document summarizes key information about organozinc compounds:
1. Organozinc compounds contain carbon-zinc bonds and were among the first organometallic compounds synthesized.
2. They are less reactive than other organometallic reagents like Grignard and organolithium compounds.
3. Organozinc compounds react through reactions like the Reformatsky reaction, Simmons-Smith reaction, Negishi coupling and Fukuyama coupling to form carbon-carbon bonds. They can also be used to introduce functional groups.
This seminar paper reviews the role of science, technology, and innovation in ensuring food security in Ethiopia. It discusses how Ethiopia has struggled with food insecurity and dependence on food aid. It outlines the objectives of reviewing how STI can address the four dimensions of food availability, access, utilization, and stability. The paper then examines various technologies that can improve agricultural productivity, food access through reductions in post-harvest losses, food nutrition through biofortification, and food stability through climate-smart agriculture and early warning systems. It concludes that STI has an important role to play in developing innovative food systems and ensuring food security in Ethiopia.
The document discusses geographic information systems (GIS). It defines GIS as a computer system for collecting, storing, analyzing and displaying spatially-referenced data. The key components of a GIS are hardware, software, data, procedures and users. GIS has functions like inputting, storing, querying, analyzing and displaying spatial data. It can be used for applications in various fields such as agriculture, transportation and environmental planning. The document also covers spatial data models, coordinate systems and map projections used in GIS.
Introduction to AI for Nonprofits with Tapp NetworkTechSoup
Dive into the world of AI! Experts Jon Hill and Tareq Monaur will guide you through AI's role in enhancing nonprofit websites and basic marketing strategies, making it easy to understand and apply.
This presentation includes basic of PCOS their pathology and treatment and also Ayurveda correlation of PCOS and Ayurvedic line of treatment mentioned in classics.
Physiology and chemistry of skin and pigmentation, hairs, scalp, lips and nail, Cleansing cream, Lotions, Face powders, Face packs, Lipsticks, Bath products, soaps and baby product,
Preparation and standardization of the following : Tonic, Bleaches, Dentifrices and Mouth washes & Tooth Pastes, Cosmetics for Nails.
Exploiting Artificial Intelligence for Empowering Researchers and Faculty, In...Dr. Vinod Kumar Kanvaria
Exploiting Artificial Intelligence for Empowering Researchers and Faculty,
International FDP on Fundamentals of Research in Social Sciences
at Integral University, Lucknow, 06.06.2024
By Dr. Vinod Kumar Kanvaria
Assessment and Planning in Educational technology.pptxKavitha Krishnan
In an education system, it is understood that assessment is only for the students, but on the other hand, the Assessment of teachers is also an important aspect of the education system that ensures teachers are providing high-quality instruction to students. The assessment process can be used to provide feedback and support for professional development, to inform decisions about teacher retention or promotion, or to evaluate teacher effectiveness for accountability purposes.
it describes the bony anatomy including the femoral head , acetabulum, labrum . also discusses the capsule , ligaments . muscle that act on the hip joint and the range of motion are outlined. factors affecting hip joint stability and weight transmission through the joint are summarized.
How to Fix the Import Error in the Odoo 17Celine George
An import error occurs when a program fails to import a module or library, disrupting its execution. In languages like Python, this issue arises when the specified module cannot be found or accessed, hindering the program's functionality. Resolving import errors is crucial for maintaining smooth software operation and uninterrupted development processes.
1. Fan Liu, Michael
Furrow
1
Hursthouse, M. B.; Motewaili, M.; O'Brien, P.; Walsh, J. R.; Jones, A. C. J. Mater.
Chem.
1991, 1, 139–140.
Kitamura, M.; Suga, S.; Kawai, K.; Noyori, R. J. Am. Chem. Soc. 1986, 108, 6071-
6072.
Zn—C
1.98 Å
n-C6H13 Et 81 61
3
H C
Zn—C
1.95 Å
80
Et 90
PhCH2CH2
N
81
Et 96
(E)-PhC(H)=CH
180 ° N CH3
N
CH3 96
Et 93
145 ° Zn
H3C
p-CH3OC6H4
H3C Zn CH3
CH3
2 H3C H3C N 3 86
N N Et 93
N CH p-ClC6H4
59
Me 91
Ph
H3C
N
H3C
CH3
N
97
Et 98
Ph
R R' % yield % ee
R H toluene, 0
°C
R R'
X-Ray structures of dimethylzinc and its adduct with 1,3,5-trimethylhexahydro-1,3,5-
triazine show that upon bis-complexation, dimethylzinc shifts from a linear geometry to a
tetrahedral geometry and that the carbon-zinc bond length increases from 1.95 Å to 1.98
Å. This is proposed to increase the nucleophilicity of the methyl groups, accelerating
addition to carbonyl compounds.
+ R'2Zn
O 2 mol % (–)-
DAIB
OH
Soai, K.; Watanabe, M.; Koyano, M. Bull. Chem. Soc. Jpn. 1989, 25, 2124–
2125.
(–)-DAIB
H3C
racemic
Bz Bz
toluene, 23°C, 14
h 93%
H (C2H5)2Zn
+ CH3
5 mol %
TMEDA
O OH
In 1986, Noyori et al. published the first highly selective procedure for the asymmetric addition of
diethyl- and dimethylzinc to aldehydes employing (–)-3-exo-(dimethylamino)isoborneol (DAIB) as
a chiral catalyst.
H3C CH3
N(CH3)3
OH
The addition of a catalytic amount of TMEDA will promote the addition of diethylzinc at
room temperature to 4-benzoylbenzaldehyde in 93% yield.
Oguni, N.; Omi, T. Tetrahedron Lett. 1984, 25, 2823–
2824.
The reactivity of dialkylzinc reagents towards ketones and aldehydes is low; the rate of addition
of Et2Zn to benzaldehyde is negligible at room temperature.
96% yield, 49%
ee
Background:
H + (C2H5)2Zn
CH3
O OH
OH
H3C
2 mol % CH3 NH2
toluene, 20 °C, 43 h
Pu, L.; Yu, H.-B. Chem. Rev. 2001, 101, 757–824.
Lemire, A.; Cote, A.; Janes, M. K.; Charette, A. B. Aldrichimica Acta 2009, 42, 71–
83. Lumbroso, A.; Cooke, M. L.; Breit, B. Angew. Chem. Int. Ed. 2013, 52, 1890–
1932.
Recent Reviews: In 1984, Oguni and Omi found that a small amount of (S)-leucinol catalyzed the
enantioselective addition (49% ee) of diethylzinc to benzaldehyde.
Chem
115
Organozinc Reagents: Asymmetric Additions to Carbonyl Compounds
Myer
s
2. Kitamura, M.; Okada, S.; Suga, S.; Noyori, R. J. Am. Chem. Soc. 1989, 111, 4028-4036. Oguni, N.;
Matsuda, Y.; Kaneko, T. J. Am. Chem. Soc. 1988, 110, 7877.
Fan Liu, Michael
Furrow
2
Itsuno, S.; Fréchet, J. M. J. J. Org. Chem. 1987, 52, 4142–4143.
Corey, E. J.; Hannon, F. J. Tetrahedron Lett. 1987, 28, 5237–
5240. Evans, D. A. Science 1988, 240, 420–426.
homochiral dimer,
less stable,
dissociates
Et Et Ar
Zn
H
3
O
Et
Ar
3
3 3 H
H C H C
O
CH
Zn
Et
O
CH O
H3C CH3
3
H C
N N 3
Zn
Et
Zn
Et H C
slow
3 3
CH CH
3 3 3 3 3
H C CH H C CH H C
CH3 R Zn
CH3
O
N
CH3
H
Ar
Et Ar Zn R
O
N
3
EtZnO H O H H
CH3 CH
heterochiral dimer,
more stable, does not
readily dissociate
H3C Zn
Et
Et
+
O 3
3
H C
O
CH
Zn Et CH3
3
3 H C
CH
N
Zn Et
CH3
H
N H3C
H3C CH3
N
CH3
R Zn
H3C CH3
R Zn O
O N
H3C H3C
CH3
CH3
H H H3C CH3
H
H3C H3C
3 O O
H C
Et2Zn H3C
N
Zn R
N
Zn R
3
N(CH3)3
OH
CH3
3
CH
CH3
H3C CH3 CH H3C CH3
H3C CH3
This observation is consistent with a mechanistic proposal involving two Zn atoms per
aldehyde:
(–)-DAIB (+)-DAIB
Kitamura, M.; Okada, S.; Suga, S.; Noyori, R. J. Am. Chem. Soc. 1989, 111, 4028–
4036.
H H3C CH3
3
3 H C
H3C 3
O
CH
H C
Zn Et +
N
R Zn
O
N
3
CH CH3
1 : 1 : 0 0 —
1 : 1 : 1 1 0
50 : 50 : 1 97 98
H3C CH3 H
aldehyde : Et2Zn : DAIB % yield % ee
92% yield, 95%
ee
toluene, 0 °C, 6
h
2 5 2
H (C H ) Zn
+
H + (C2H5)2Zn
CH3
CH3
cat. (–)-
DAIB
O
O OH
8 mol % (–)-DAIB
15 % ee
OH
A non-linear dependence of product ee on catalyst ee was observed. Heterochiral dimerization
to form an unreactive species was invoked to account for in situ amplification of product ee:
Mechanism:
The stoichiometry of aldehyde, diethylzinc, and DAIB ligand determines reactivity: alkylation
occurs only when the ratio of Et2Zn : DAIB is greater than 1:
Chem
115
Organozinc Reagents: Asymmetric Additions to Carbonyl Compounds
Myer
s
3. Reeder, M. R.; Gleaves, H. E.; Hoover, S. A.; Imbordino, R. J.; Pangborn, J. J. Org. Process
Res.
Dev. 2003, 7, 696–
699.
Kim, J. G.; Walsh, P. J. Angew. Chem. Int. Ed. 2006, 45, 4175–
4178.
Fan Liu, Michael
Furrow
3
TEEDA
H3C CH3
SO2CH3
3 3 (5 mol%)
H C CH
H3C
unstable
above –50
ºC
stable N N TEEDA
(equiv) yield ee
0 –
2
0.8 99
92
SO2CH3
90% N
OH
H Li ZnCl Br
THF, –60
ºC
O
H3C CH3
ZnCl2 N MTBE
hexane
s
N O 1. n-BuLi N O O
N O
Pd(PPh 3)4
(5 mol%)
60 ºC
Transmetallation with a Zinc Salt:
Substrates that are less readily prepared by direct reduction can be prepared by treatment of
a Zinc(II) halide with two equivalents of alkyllithium or alkylmagnesium halide:
Cote, A.; Charette, A. B. J. Am. Chem. Soc. 2008, 130, 2771–2773.
• N,N,N,N-tetraethylethylenediamine (TEEDA) can be used to scavenge salts and the resulting in situ
formed zinc reagents function in catalytic asymmetric addition reactions to aldehydes:
3. O
H OH
Br1. n-BuLi 2. ZnCl2
Choi, B. S.; Chang, J. H.; Choi, H.-W.; Kim, Y. K.; Lee, K. K.; Lee, K. W.; Lee, J. H.; Heo, T.;
Nam,
D. H.; Shin, H. Org. Process Res. Dev. 2005, 9, 311–313.
0 → 23 ºC
> 95%
H3C H3C
MgCl Zn
2 x + Zn(OCH3)2 + 2 CH3OMgCl
CH3 CH3 CH3
CH3
2
Et O
11.5
kg
10.6 kg
THF, 70
ºC
Cl Cl
2 2 10.0
kg
2. 6N HCl
72%
EtO C Br EtO C ZnBr
Cl Zn(OCH3)2 can also be used. The byproduct, CH3OMgCl, precipitates from the reaction mixture
and salt-free ethereal solutions of diorganozinc can be obtained after filtration or centrifugation:
Cl EtO2C F
1. Zn
MsOH (5
mol%)
O
NC F
von dem bussche-Hünnefeld, J. L.; Seebach, D. Tetrahedron 1992, 48, 5719–
5730. Brubaker, J. D.; Myers, A. G. Org. Lett. 2007, 9, 3523–3525.
O
methanesulfonic acid can be used to activate zinc
metal:
N
>80%
93%
ee
CH3
OBn OBn
200 ºC
<30 mmHg
89 %
Et2Zn
EtI EtBr
+
Zn-Cu
neat, reflux
distillation
2
+
BrZnI
H N N
[EtZnI]
+
[EtZnBr]
Et Zn THF, –75 ºC
OLi
O O
Schlenk
Equilibrium
O OH
3.
filtration
Zn
ZnCl2
(1.0 M in Et2O)
2.
dioxane
(1.0 M in Et2O)
(salt free)
MgBr
1.
Metallic Zinc Insertion:
One of the early methods involves treatment of an alkyliodide or bromide with zinc dust or an
activated form of Zn, such as zinc-copper couple (Zn(Cu)). The method requires rather harsh
conditions and is limited to low molecular weight dialkylzinc species due to the need to distill
the products while avoiding competitive Wurtz coupling:
1,4-Dioxane forms insoluble complexes with magnesium halides and allows the synthesis of
diorganozinc reagents that were not commercially available to subsequently be used in
asymmetric additions to carbonyl compounds:
Lemire, A.; Cote, A.; Janes, M. K.; Charette, A. B. Aldrichimica Acta 2009, 42, 71–
83. Knochel, P.; Perea, J. J. A.; Jones, P. Tetrahedron 1998, 54, 8275–8319.
In many cases, lithium or magnesium halide byproducts must be removed to avoid salt
complexation with chiral additives in subsequent enantioselective processes.
Myers
Preparation of Organozinc Reagents:
Chem
115
Organozinc Reagents: Asymmetric Additions to Carbonyl Compounds
4. Kneisel, F. F.; Dochnahl, M.; Knochel, P. Angew. Chem. Int. Ed. 2004, 43, 1017–
1021.
Wipf, P.; Xu, W. Org. Synth. 1997, 74, 205–
211. Fan Liu, Michael
Furrow
4
CH3
Li(acac)2
H O O H H O
Cp2ZrHCl ZnMe2
CH2Cl2
0 → 23 ºC
toluene
–60 → 0 ºC
ZrCp2Cl > 86% Zn
OTBDPS OTBDPS OTBDPS 3
H O
H3CO Zn OCH3 H3CO Zn
O CH
i-Pr
Li+
OAc OAc AcO O
organozirconium
:
CH3
H3CO I
Vettel, S.; Vaupel, A.; Knochel, P. J. Org. Chem. 1996, 61, 7473–
7481.
OAc
H O H O
OPiv OPiv
COD (2 mol%), neat, 50–60
°C
> 40%
2 x
Li(acac)2
Et2Zn (0.6 equiv), Ni(acac)2 (1 mol%) i-Pr
2
) Zn H3CO I H3CO Zn
i-Pr2Zn
Li(acac) 2 (10 mol%)
Et2O, NMP 25
ºC, 12 h
>90%
OAc OAc
organonickel
:
Aryl and alkenyl iodides can undergo halogen-zinc exchange with i-P2rZn. Li(acac)2 activates
the intermediate mixed diorganozinc as an ate complex and promotes the second exchange:
Langer, F.; Schwink, L.; Devasagayaraj, A.; Chavant, P.-Y.; Knochel, P. J. Org. Chem. 1996,
61, 8229–8243.
Powell, N. A.; Rychnovsky, S. D. J. Org. Chem. 1999, 64, 2026–
2037.
> 86%
2 2
EtO C 2. Et Zn, neat, 0 °C t-Bu
EtO2C 2
) Zn TMSOTf, CH2Cl2
–78 ºC, 67%
0.1 mm
Hg 50
°C
2
I OEt EtO ) Zn
CO2Et O O
1. Et2BH, Et2O, 0 °C CO2Et
OEt
O O
n-Hex
O O
t-Bu
O
Et2Zn CuI
(3 mol%)
neat, 50
°C
organoboron
:
Milgram, B. C.; Liau, B. B.; Shair, M. D. Org. Lett. 2011, 13, 6436–
6439.
Substrate decomposition occurred in the absence of
ZnEt2.
Rozema, M. J.; Eisenberg, C.; Lütjens, H.; Ostwald, R.; Belyk, K.; Knochel, P. Tetrahedron
Lett.
1993, 34, 3115–3118.
Rozema, M. J.; Sidduri, A.; Knochel, P. J. Org. Chem. 1992, 57, 1956–1958.
n-Hex OAc
3 3
82% CH
3
H
OTBS
H C
OBn MoOPH OBn
H
OTBS
OBn
H
OTBS
Ph
Si
Ph
Si
H3C
CH
0.1 mm Hg, 50
°C
> 95%
OPiv
OPiv Me2PhSiLi,
ZnEt2;
AcOCH2(CH2)3CH2I (AcOCH2(CH2)3CH2)2Zn
HO
O O
OZn–Et2Li+
OPiv
Et2Zn, CuI (0.1 mol%)
neat, 50 °C;
organolithium
:
Halogen-Diorganozinc Exchange:
Iodine-zinc exchange reactions have been used to prepare dialkylzinc species containing
esters, nitriles, chlorides, sulfonamides, and boronic acids. CuI or UV light were found to
accelerate the reaction. Removal of excess Et2Zn and EtI was necessary to drive the reaction:
Chem
115
Organozinc Reagents: Asymmetric Additions to Carbonyl Compounds
Myers
Transmetallation with a Diorganozinc Reagent:
Functionalized diorganozinc reagents can be prepared via transmetallation of
organolithium, organoboron, organonickel, and organozirconium with dimethyl-, diethyl-, or
diisopropylzinc:
5. Nugent, W. A. Org. Lett. 2002, 4, 2133–
2136.
Fan Liu, Michael
Furrow
5
Berger, S.; Langer, F.; Lutz, C.; Knochel, P.; Mobley, T. A.; Reddy, C. K. Angew. Chem., Int.
Ed. Engl. 1997, 36, 1496–1498.
H3C H3C
86%, > 94%
ee
hexanes,
toluene 0 ºC,
91%
99% ee
H3C H H3C Et
Cl
3 (5 mol%) 2
Et O, –20 °C
O OH
2
Et Zn H
OH
6 (8 mol%)
Ti(Oi-Pr)4
O
Watanabe, M.; Soai, K. J. Chem. Soc., Perkin Trans. 1, 1994, 3125–
3128.
(Cl(CH2)4)2Zn + (TMSCH2)2Zn (Cl(CH2)4)Zn(CH2TMS)
neat, 25
°C
O OH
H toluene, 0 ºC
82%, 96%
ee
Et
Ph Ph
Unsymmetrical dialkyl zinc containing a trimethylsilylmethyl group as a non-transferable group
can be prepared to avoid losing one equivalent of valuable alkyl zinc precursor:
Et2Zn
n-BuLi, 2 (8 mol%)
O O
Chemoselective addition to aldehydes can be achieved in the presence of
ketones:
Yoshioka, M.; Kawakita, T.; Ohno, M. Tetrahedron Lett. 1989, 30, 1657–1660.
Takahashi, H.; Kawakita, T.; Yoshioka, M.; Kobayashi, S.; Ohno, M. Tetrahedron Lett. 1989,
30, 7095–7098.
Hayasaka, T.; Yokoyama, S.; Soai, K. J. Org. Chem. 1991, 56, 4264–
4268.
toluene, –30
ºC
99%, 98% ee
Ph H Ph n-Bu
O OH
Ph H Ph Et
hexanes, 0
ºC
94%, 95% ee
n-Bu2Zn, Ti(Oi-Pr)4
6 (2 mol%)
O OH
Schmidt, B.; Seebach, D. Angew. Chem. Int. Ed. 1991, 30, 99–
101.
Et2Zn
1 (6 mol%)
5 6
Ligand 1 extends the scope of the initial DAIB reaction to include aliphatic
aldehydes:
7 H3CO H3CO
toluene
0 → 23 ºC, 89%
98% ee
toluene
–75 → 23 ºC, 86% H3CO
94% ee
NHTf Et H Et
Ph
Ph N (1.2 equiv)
O
O 3
3 4
OH OH
CH
H C Et2Zn O Ti(Oi-Pr) 5 (2 equiv)
NHTf
CH3
H3C
OH
OH
O
O O O
Ti
O O
Ph
Ph
Ph Ph Ph Ph N
Using 5 as a chiral additive, either enantiomer of the product can be obtained by changing
the reaction conditions:
Et2Zn
5 (10 mol%)
1 2 3 4
Nugent, W. A. Chem. Commun. 1999, 1369–
1370.
HO N(n-Bu)2 H3C
N
CH3
3
Ph CH
N
OH
CH3 CH3
Ph
Ph
OH
hexanes,
toluene 0 ºC,
94%
99% ee
O
HO N H3C CH3 H Et
H3C H3C
O OH
Et2Zn
ent-4 (5 mol%)
O
shown
here:
3-exo-morpholinoisoborneol (MIB), 4, more stable and easier to prepare than DAIB, catalyzes
enantioselective additions to aldehydes with similar selectivity and efficiency. It also shows
improved selectivity with α-branched, aliphatic aldehydes:
Chem
115
Organozinc Reagents: Asymmetric Additions to Carbonyl Compounds
Myers
Alkylzinc Addition to Aldehydes:
A variety of chiral catalysts and ligands have been developed that promote the addition of
dialkylzinc reagents to give enantiomerically enriched secondary alcohols. Only a few
representative ones are
6. Wipf, P.; Ribe, S. J. Org. Chem. 1998, 63, 6454–
6455. Fan Liu, Michael
Furrow
6
Cl
toluene, –30 ºC
83%, 97%
ee
H
Langer, F.; Schwink, L.; Devasagayaraj, A.; Chavant, P.-Y.; Knochel, P. J. Org. Chem. 1996,
61, 8229–8243.
Cl
O
Ginnol
3 n-Bu
n-Bu
n-Bu H 3 2
Zn
CH
3 3 SH N(CH )
CH H C
THF, –60 → 0 °C
95%
OH
CH3
1.Cp2ZrHCl
CH2Cl2, 23 ºC
2.Me2Zn
toluene, –65 ºC
Bu2Cu(CN)Li2
(10 mol%)
OH
69%, 92%
ee
Oppolzer, W.; Radinov, R. N. Helv. Chim. Acta. 1992, 75, 170–173.
Oppolzer, W.; Radinov, R. N.; De Brabander, J. Tetrahedron Lett. 1995, 36, 2607–
2610.
CH3 CH3
H
Br
60%, 82%
de
O OH H3C
3
H C
(Br(CH2)5)2Zn
Ti(Oi-Pr)4
6 (8 mol%)
toluene
–60 → –20 °C
O O
O O
2. Et2Zn
(–)-DAIB (1 mol%)
H
1. (Cy)2BH•S(CH3)2
hexanes
–20 → 23 °C
HO
O
Fürstner, A.; Langemann, K. J. Am. Chem. Soc. 1997, 119, 9130–
9136.
(–)-
Gloeosporone
Mixed organozinc reagents, formed via transmetallation of organoboron or organozirconium with
dialkylzinc, can be used to form enantiomerically enriched allylic alcohols in the presence of a
chiral amino alcohol catalyst:
CH3
Oppolzer, W.; Radinov, R. N. Tetrahedron Lett. 1988, 29, 5645–
5648.
H
O
O OH O
hexanes, 0
ºC
90%, 96%
ee
O
Zn
H n-Bu
n-Bu
88% yield, >98%
ee
3 OH
H C (20 mol%)
O
H3CO H H3CO CH3
N N(CH3)2
3 3
OCH O OCH OH
OH
(n-C5H11)2Zn
Ti(Oi-Pr)4
6 (20 mol%)
toluene
–78 → –20 °C
The first example of catalytic asymmetric vinylzinc additions to aldehydes was reported using
a
chiral diaminoalcohol ligand:
H3C CH3
Alkenylzinc Addition to Aldehydes:
Myers
Dialkylzinc Reagents in Synthesis:
Chem
115
Organozinc Reagents: Asymmetric Additions to Carbonyl Compounds
7. Kerrigan, M. H.; Jeon, S.-J.; Chen, Y. K.; Salvi, L.; Carroll, P. J.; Walsh, P. J. J. Am. Chem.
Soc.
2009, 131, 8434–
8445.
Fan Liu, Michael
Furrow
7
O
50%, 95%
ee
H OHC
(–)-Longithorone A CH3
Layton, M. E.; Morales, C. A.; Shair, M. D. J. Am. Chem. Soc. 2002, 124, 773–775.
H O
Cy
Et Et Cy
Zn B
O
3
CH
n-Bu n-Bu O
H
2
Et Zn
Cy Cy
OH n-Bu O
H H
H3C
TMEDA
4 (5 mol%)
toluene, 0
ºC
97% yield, 90%
ee
0 → 23 °C 2. TBAF, THF
0 → 23 °C
Br Br OH
TBSO I
Br n-Bu n-Bu 1. as above
n-Bu HO OCH3
–78 → 0 °C
Cy2B
2 +
2. Et Zn
1. (Cy)2BH
toluene
H H
Cy
Cy B
Et
HO
O
OCH3
CH3
H
Tri-substituted Z-allylic alcohol can also be
prepared:
TBSO
TIPS CH3
91% yield, 95%
ee
TMS CH3 OH
+
Salvi, L.; Jeon, S.-J.; Fisher, E. L.; Carroll, P. J.; Walsh, P. J. J. Am. Chem. Soc. 2007, 129,
16119– 16125.
OCH3
3. H3C NMe2
Ph OLi
(2.5 equiv)
toluene, 0°C
TMS CH3
I TBSO
2. ZnBr2,
Et2O, 0 ºC
H
69%, 93%
ee
S 3
2
BCy2 TIPS CH
Et O, –78°C
–78 °C
O OTBDPS 1. t-BuLi
S H
OH OTBDPS H
Et2Zn
TEEDA
4 (5 mol%)
–78 → 23 °C
Alkenylzinc Reagents in Synthesis:
DeBerardinis, A. M.; Turlington, M.; Pu, L. Angew. Chem. Int. Ed. 2011, 50, 2368–
2370.
Cl
OTBDPS
H3C
O
94%, >99%
ee
3
H C H O
H
Cy B
Cy
3
Li H H CO n-Bu
CH2Cl2
H3CO
–20 → 23 °C Cl
Cl (26 mol%)
n-Bu NMP, 0 ºC
7 (10 mol%) H CH3
OTBDPS 2
OTBDPS
Cy2B HO
MTBE I 3
O CH
Et2Zn
Li(acac)
2. t-BuLi
–78 → 23 °C
2 H
1. (Cy) BH
H3C CH3
Hydride migration from a boron ate complex provides access to enantiomerically enriched Z-
allylic alcohols:
Direct transmetallations from vinyl iodides provide alkenylzinc reagents not accessible
through hydroboration or hydrozirconation:
Chem
115
Organozinc Reagents: Asymmetric Additions to Carbonyl Compounds
Myer
s
8. Ishizaki, M.; Hoshino, O. Tetrahedron: Asymmetry 1994, 5,
1901.
Magnus, N. A.; Anzeveno, P. B.; Coffey, D. S.; Hay, D. A.; Laurila, M. E.; Schkeryantz, J. M.; Shaw,
B. W.; Staszak, M. A. Org. Process Res. Dev. 2007, 11, 560–
567.
Fan Liu, Michael
Furrow
8
OTBS
17.6 kg
–5 → –10 ºC
47.6 kg
88%, >94%
ee
H
60 ºC CN The low yields in these reactions was attributed in part to competitive addition of ethyl groups to
the aldehydes.
toluene O TBSO
B
O O
Et2Zn (20 mol%)
OH
O
B
B
Ph OH
Ph
Ph
N
OTBS OTBS
DiMPEG = dimethoxy
poly(ethyleneglycol)
Bolm, C.; Rudolph, J. J. Am. Chem. Soc. 2002, 124, 14850–
14851.
R1 R2 T (°C) % yield % ee
C6H5 C6H5 0 64 90
C6H5 c-Hx 0 88 91
C6H5 t-Bu 0 61 95
Ph3Si c-Hx 23 55 91
C6H13 t-Bu 23 67 87
CN
C6H13 C6H5 23 41 78
Cl 8
toluene, –10 ºC
O
H p-ClC6H4
toluene
60 ºC,
>95%
Ph
Ph ZnEt
Ph B(OH)2
Et2Zn OH N
OH
N
OH
Fe Ph Ph
(S)-cat.
t-Bu
8 (10 mol%)
DiMPEG
(10 mol%)
O O
H3C CH3
CH3
Widely available aryl boronic acids and boroxines can be directly transformed into arylzinc
reagents and undergo enantioselective arylation of aldehydes with excellent selectivity:
R1
THF,
reflux
THF
DeBerardinis, A. M.; Turlington, M.; Ko, J.; Sole, L.; Pu, L. J. Org. Chem. 2010, 75, 2836–
2850.
R2
R1 ZnEt
R1
Et2Zn
OH
R2 H
10 mol % (S)-cat.
OCH3 OCH3
NMP, 0
ºC
THF, 0
ºC
23 ºC
O
7 (10 mol%)
I H
Et2Zn
Li(acac)2
(26 mol%)
OH
O
Mixed alkylalkynylzinc reagents can be prepared directly from terminal acetylenes and have
been shown to undergo catalyzed 1,2-additions to aldehydes with good enantioselectivities.
Ligand 7 (see page 5) has been found to promote highly enantioselective additions of
diphenylzinc and functionalized diaryl zinc to aromatic and aliphatic aldehydes:
Wu, X.-F.; Neumann, H. Adv. Synth. Catal. 2012, 354, 3141–
3160. Trost, B. M.; Weiss, A. Adv. Synth. Catal. 2009, 351, 963–
983.
Pu, L. Tetrahedron 2003, 59, 9873–9886.
Unlike dialkylzinc additions, diphenylzinc additions to aldehydes take place smoothly even without
a catalyst. This background reaction has made it more difficult to develop enantioselective
variants.
Schmidt, F.; Stemmler, R. T.; Rudolph, J.; Bolm, C. Chem. Soc. Rev. 2006, 35, 454–470.
Recent Reviews:
Alkynylzinc Additions to Aldehydes
Chem
115
Organozinc Reagents: Asymmetric Additions to Carbonyl Compounds
Myers
Arylzinc Addition to Aldehydes:
9. 77%, 98%
ee
Anand, N. K.; Carreira, E. M. J. Am. Chem. Soc. 2001, 123, 9687–
9688.
Fan Liu, Michael
Furrow
9
Diez, S. R.; Adger, B.; Carreira, E. M. Tetrahedron. 2002, 58, 8341–
8344.
3
Et N, toluene, 60 °C
3
CH
Zn(OTf)2 (20 mol%) CH3
H OTMS
CH3
CH3
3
H CH
CH3
+
H3C 3
H C
OTMS
O
OH
(+)-N-methyl
ephedrine (22
mol%)
OH
O 3
H CH
Zn(OTf)2, Et3N
toluene, 60 °C
72%, 99% ee, dr = 92 : 8
CH3
H
+
CH3
(–)-N-methyl ephedrine
3
CH
The system is less effective for aromatic aldehydes because of a competitive Cannizzaro
reaction.
OBz OBz
It was shown that by raising the reaction temperature to 60 °C, the in situ zinc acetylide
formation and addition reaction can be made catalytic in both zinc and chiral ligand.
The resulting terminal acetylene can be used to prepare enantiomerically enriched 1,4 -
diols:
Boyall, D.; Lopez, F.;Sasaki, H.; Frantz, D.; Carreira, E. M. Org. Lett. 2000, 2, 4233–
4236.
Frantz, D. E.; Fassler, R.; Tomooka, C. S.; Carreira, E. M. Acc. Chem. Res. 2000, 33, 373–381.
Boyall, D.; Frantz, D.; Carreira, E. M. Org. Lett. 2002, 4, 2605–2606.
For an investigation on the reaction mechanism, see: Fässler, R.; Tomooka, C. S.; Frantz, D.
E.; Carreira, E. M. Proc. Natl. Acad. Sci. 2004, 101, 5843–5845.
Frantz, D. E.; Fassler, R.; Carreira, E. M. J. Am. Chem. Soc. 2000, 122, 1806–1807.
R1 R2 yield (%) ee (%)
n-C5H11 CH2CH2Ph 94 97
n-C5H11 Ph 90 97
i-Pr Ph 96 92
Ph Ph 82 93
2 3
toluene, 23 °C;
benzoyl
chloride
Zn(OTf) , Et N
Ph OH
(+)-N-
methylephedrine
R2 toluene, 110
ºC
1
H3C CH3
H
R % overall yield % ee
n-C3H7 68 99
n-C5H11 71 98
t-Bu 65 98
c-C6H11 73 99
TIPSO(CH2)2 71 97
R H R H (–)-N-methyl ephedrine R
R1
OH
H R2
(+)-N-methyl ephedrine
Zn(OTf)2, Et3N
toluene, 23 °C
2 3
3 2 K CO
O H C NMe R
O OBz
OH cat. 18-cr-
6
H OBz
OH
CH3
CH3
All reagents are stoichiometric or
superstoichiometric.
Protection of the 2° propargylic alcohol prior to cleavage of acetone from the adducts leads
to improved yields.
The reactions can be carried out without rigorous exclusion of oxygen or moisture using
reagent- grade toluene (84–1000 ppm H2O).
Enantioselective additions of 2-methyl-3-butyn-2-ol to aldehydes provide access to optically
active terminal acetylenes after cleavage of acetone from the products.
In 2000, Carreira et al. published an in situ preparation of alkynylzinc reagents and their addition
to aldehydes with excellent enantioselectivities and yields.
Chem
115
Organozinc Reagents: Asymmetric Additions to Carbonyl Compounds
Myer
s
10. 1
Topic, D.; Aschwanden, P.; Fässler, R.; Carreira, E. M. Org. Lett. 2005, 7, 5329–
5330.
Fan Liu, Michael
Furrow
10
R O 3
CH
H H
H
O
N 1
O CH3
Li, X.; Lu, G.; Kwok, W. H.; Chan. A. S. C. J. Am. Chem. Soc. 2002, 124, 12636–12637.
85%, 99%
ee
3 2
Zn(CH ) , THF, 0 °C
R2
Ph OH
Ligand
R Ph
toluene, 23 °C
92%, dr = 96 : 4
–O +
6 4
p-BrC H H
H
+ p-BrC6H4 H3C NHTs
ZnCl2, Et3N HO
N
Xc* O H Ph
(S)-BINOL (10 mol%)
Ligand (10 mol%)
OH
H3C CH3
O O
A highly effective two-catalyst system was reported for the addition of zinc acetylide to aromatic
aldehydes. The stereochemistry of BINOL determines the stereochemistry of the products, while
the second ligand improves catalytic activity and enantioselectivity:
The use of ZnCl2 homogenizes the reaction mixture and obviates the need for N,N-
dimethylethanolamine:
Fassler, R.; Frantz, D. E.; Oetiker, J.; Carreira, E. M. Angew. Chem., Int. Ed. Engl. 2002,
41, 3054–3056.
Lowering the loading of Zn(OTf)2 to 20 mol% resulted in lower selectivites and isolated
yields.
Knöpfel, T. F.; Boyall, D.; Carreira, E. M. Org. Lett. 2004, 6, 2281–2283.
O
R
HO O R
6 11
>98% ee
R = c-C H , 83%,
O
>98% ee
1. KOH, PrOH, 97 ºC H3C
1. DMSO, 100 ºC Ph
R = i-Pr, 97%, O
H3C
N
CH3 Ph 88 95:5
i-Pr C(OH)Me2 98 96:4
t-Bu Ph 91 97:3
Ph SiMe3 88 95:5
Ph Ph
R2 overall yield
(%)
dr
R1
O O
O O 2
Et3N, CH2Cl2, 23 ºC
Ph Ph R
O Zn(OTf) (60 mol%)
CH3
2
R
3
H O H
CH
HOHN H R , TiCl4
pyridine, THF
–78 → 23 ºC
O
MeOH, H2O, 60 ºC H3C H3C H
O O
+ Ph
H3C
N
H3C
N
O
2
H NOH•HCl, NaOAc
OH
HN
R1
H3C CH3
O O
The oxazepanedione shown below, prepared in 3 steps from ephedrine and dimethyl malonate,
undergoes condensation with aldehydes mediated by TiCl4. Conjugate addition of zinc
alkynylides followed by hydrolysis and decarboxylation give β-alkynyl acids in good yields and
selectivities:
O 3 2 2
3 Et N, CH Cl , 23 °C;
CH R2
H H
R1 H
Pinet, S.; Pandya, S. U.; Chavant, P. Y.; Ayling, A.; Vallee, Y. Org. Lett. 2002, 4, 1463–
1466.
O CH3
O R1
–O +
N
N
c
HO X *
O O Bn
H R2
Zn(OTf)2 (0.5 equiv)
Me2NCH2CH2OH (0.5 equiv)
81% H3C
H3C
NHBn
N
3 3
H C CH OH
Zn, AcOH, H2O
Ph
Ph
Hydroxylamines are readily reduced to free
amines:
A mannose-derived auxiliary was employed to promote diastereoselective alkynylzinc additions
to nitrones. The nitrone auxiliary was prepared from mannose, acetone and N-hydroxylamine.
Chem
115
Organozinc Reagents: Asymmetric Additions to Carbonyl Compounds
Myer
s
11. Lehr, K.; Mariz, R.; Leseurre, L.; Gabor, B. Fürstner, A. Angew. Chem. Int. Ed. 2011, 50,
11373–
11377. Fan Liu, Michael
Furrow
11
(–)-Tulearin
C
CH3
OH
H3C
Scheerer, J. R.; Lawrence, J. F.; Wang, G. C.; Evans, D. A. J. Am. Chem. Soc. 2007, 129,
8968– 8969.
O O CH3
OH HO
7 steps
C5H11
CH3
3 3
3 3
CH CH
OH CH OH CH
(–)-Salvinorin
A
2. I2, –20 ºC, 99%
(CH3O)2HC H3CO2C
CH3
3
CH
OH I
7 steps 1. Red-Al, Et2O
3Å MS, 0 → 23 ºC C5H11
Me
O C5H11
O
BOMO
AcO
H
O O
O
H
O
H
Me
toluene, 23 ºC
91%, dr > 95 : 5
CH3
O CH3
2 2
Zn(OTf) , i-Pr NEt
+
5 11
C H
O H
O (+)-N-Me-ephedrine
Kleinbeck, F.; Carreira, E. M. Angew. Chem. Int. Ed. 2009, 48, 578–
581.
–78 → 5 ºC, 99%
single
diastereomer
TBAF, DMF,
THF
(–)-Bafilomycin A1 CH3 CH3 OH
(CH3O)2HC
H3C CH3
O
CH3 CH3 OCH3 CH3
HO 13
steps
TBDPS
O
HO
10
steps
CH3 O
O
BOMO H3C
H3C
O OH O
Ph CH3 OTBS
CO2CH3
OH CH(OMe)2
H3C
O CH3
OTE
S
H3CO2C
H3C CH 3
O O
OH
i-Pr
O
H3CO CH3 CH3 O CH3 CH3
H3CO
Zn(OTf)2, Et3N
toluene, 23 ºC
90%, dr = 6 : 1
CH3
H + H 3 3
(–)-N-Me-ephedrine CH CH O
Ph 3
H C
CH3 OTBS
CO2CH3
O CH(OMe)2
Zn(OTf)2, i-Pr2NEt
toluene, 23 ºC
91%, dr > 95 : 5
H3C
H +
H3CO2C (+)-N-Me-ephedrine
OTES
TBDPS
O
3 3
3
H CO CH CH
H3C CH 3
O O
Alkynylzinc Reagents in Synthesis:
Chem
115
Organozinc Reagents: Asymmetric Additions to Carbonyl Compounds
Myer
s
12. Li, H.; Walsh, P. J. J. Am. Chem. Soc. 2005, 127, 8355–
8361. Fan Liu, Michael
Furrow
12
Chen, C.; Hong, L.; Xu, Z.-Q.; Liu, L.; Wang, R. Org. Lett. 2006, 8, 2277–
2280.
92%, 92%
ee
This method is only effective for aromatic
ketones.
Zn(CH3)2, Ti (Oi-Pr)4
toluene, 23 ºC
9 (5 mol%)
CH3
H3C H3C
O H3C OH
Ph
hexanes, –18 ºC
83%, 94% ee
CH3 Ph
+
HO CH3
F
F O
11 (1 mol%)
Et2Zn
3
Zn
H C
1.Cp2ZrHCl
CH2Cl2, 23 ºC
2. Zn(CH3)2
toluene, –78 ºC
Saito, B.; Katsuki, T. Synlett. 2004, 1557–
1560.
Li, H.; Walsh, P. J. J. Am. Chem. Soc. 2004, 126, 6538–
6539.
90%, 95%
ee
toluene, –78
ºC
3 2
2. Zn(CH ) Ph
CH2Cl2
toluene, 23 ºC
61%, 87% ee
3
Ph n-Pr Ph
Zn
H C
Ph
Ph CH3
9 (10 mol%)
Zn(CH3)2, Ti(Oi-Pr)4
toluene, 23 ºC
H3C OH
Ph
+
1. Cp2ZrHCl
CH2Cl2, 23 ºC
HO n-Pr
O
3. O 10 (8 mol%)
(CH3)2Zn
Garcia, C.; Larochelle, L K.; Walsh, P. J. J. Am. Chem. Soc. 2002, 124, 10970–
10971. Yus, M.; Ramon, D. J.; Prieto, O. Tetrahedron: Asymmetry 2002, 13, 2291–
2293.
CH2Cl2
toluene, 23 ºC
53%, 93% ee
t-Bu CH3 t-Bu
CH3 CH3
+
hexanes
toluene, 23
ºC
78%, 99%
ee
HO CH3
O
10 (8 mol%)
(CH3)2Zn
CH3
9 (2 mol%)
Et2Zn, Ti(Oi-Pr)4
O OH
CH3
Et
10 11
HO CH3
H3C OH 9
OH
N
CH3
Ph
Ph
H3C O O
O S NH HN S O
Ph
N N
OH HO
Ph Ph
Using Ti(Oi-Pr)4 as a Lewis acid, ligand 9 catalyzes the formation of tertiary alcohols with high
selectivity:
Salen ligand 10 and Schiff base ligand 11 were found to promote efficient addition of zinc
acetylides to ketones:
Chem
115
Organozinc Reagents: Asymmetric Additions to Carbonyl Compounds
Myers
Asymmetric Addition to Ketones:
Ketones are less reactive than aldehydes and often give 1,2-addition products in lower
yields because of competitve enolization or reduction of the carbonyl group.