ARE WE THERE YET?OUR JOURNEY FROM SIMPLE CLASSICAL CHEMISTRY   TO TRANSFER-HYDROGENATION OF ALKENES,      TO NEW CYCLOHEXY...
POST-GRADUATE SYMPOSIUM IN 1998
PALLADIUM-CATALYSED TRANSFER HYDROGENATION OF ALKENES INTHE PRESENCE OF ZINC POWDER AND VARIOUS ORGANIC ACIDS   Classic hy...
PALLADIUM-CATALYSED TRANSFER HYDROGENATION             OF ALKENES IN THE PRESENCE OF ZINC POWDER AND                      ...
CATALYTIC CYCLE OF THE REDUCTION REACTION                                                                                 ...
ENATIOSELECTIVE VERSION                          PdCl2, Zn,               CO2H       Chiral organic acid                  ...
BEST SYNTHESIS DISCUSSION FORUM                    http://totallysynthetic.com/blog/………..An intriguing paper has been publ...
SYNTHETIC APPROACHES TO CYCLIC                            β-AMINO                       ACID DERIVATIVES                  ...
OUR OXANORBORNYL APPROACHES TO CYCLIC β-AMINO ACID                   DERIVATIVES 1. Diels-Alder reaction of furan and (E)-...
D-A REACTION OF ETHYL (E)-3-NITROACRYLATE AND FURAN                                                            I          ...
COMPOUNDS WE PREPARED FROM THE OXANORBORNYL β-AMINO ACID  OH       NH2                                              CO2Et ...
BASE-MEDIATED ELIMINATION OF THE OXYGEN BRIDGEO                                   EtO2C                              CO 2E...
TOWARDS TRIHYDROXYCYCLOHEXYL β-AMINO ACIDS            CO2Et MCPBA, NaHCO3, CH2Cl2                         CO2Et           ...
TOWARDS TRIHYDROXYCYCLOHEXYL β-AMINO ACIDS            CO2Et MCPBA, NaHCO3, CH3CN                            CO2Et         ...
TYPICAL NMR SPECTRA                              CO2Et            AcO                                         AcO         ...
DIELS-ALDER REACTION OF FURAN AND MALEIC ANHYDRIDE               O                                             O          ...
LEWIS ACID MEDIATED OPENING OF BICYCLIC β-AMINO ACID AND SYN-DIHYDROXYLATION                                              ...
ANTI-DIHYDROXYLATION THROUGH EPOXIDATION                     OAc                                        OAc               ...
http://www.scirus.com/      is the most comprehensive scientific research tool on the web. With over 370million scientific...
BACKGROUND TO CYCLODIMERIZATION OF STYRENE OXIDES                                                O                    O   ...
CYLODIMERIZATION OF STYRENE OXIDES
CYCLODIMERIZATION OF STYRENE OXIDE        mCPBA, CH2Cl2,                                   O        NaHCO3, 25 oC,        ...
CYCLODIMERIZATION OF CHLOROSTYRENE OXIDES                                    O                                            ...
POSSIBLE MECHANISM OF THE CYCLODIMERIZATION REACTION                                                                      ...
CYCLODIMERIZATION OF METHYLSTYRENE OXIDE                                     Me             O                             ...
CYCLODIMERIZATION OF METHOXYSTYRENES                                MeO               mCPBA, CH2Cl2,                 O    ...
ARE WE THERE YET?                        SUMMARYO            cat. PdCl2, Zn, acid,         O       CO2Et                  ...
ACKNOWLEDGEMENTSResearch associates          Financial assistance Dr P. G. Steel              University of BotswanaDr ...
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Are we there yet

  1. 1. ARE WE THERE YET?OUR JOURNEY FROM SIMPLE CLASSICAL CHEMISTRY TO TRANSFER-HYDROGENATION OF ALKENES, TO NEW CYCLOHEXYL β-AMINO ACIDS AND TO CYCLODIMERIZATION OF STYRENE OXIDES Ishmael B. Masesane Chemistry Department University of Botswana
  2. 2. POST-GRADUATE SYMPOSIUM IN 1998
  3. 3. PALLADIUM-CATALYSED TRANSFER HYDROGENATION OF ALKENES INTHE PRESENCE OF ZINC POWDER AND VARIOUS ORGANIC ACIDS Classic hydrogenation O O CO2Et H2, Pd/C, Solvent CO2Et NHBoc NHBoc Avoiding hydrogen gas for safety reasons
  4. 4. PALLADIUM-CATALYSED TRANSFER HYDROGENATION OF ALKENES IN THE PRESENCE OF ZINC POWDER AND VARIOUS ORGANIC ACIDS O cat. PdCl2, Zn, acid, O CO2Et CO2Et acetonitrile, 25 oC, 16 h NHBoc NHBoc Entry Organic acid Isolated yield (%) 1 HCO2H 96 2 CH3CO2H 94 3 CH3CO2NH4 97 4 PhCO2H 93 10% PdCl2, Zn, CH3CO2H CO2H CO2H acetonitrile, 25 oC 84% 10% PdCl2, Zn, CH3CO2H, acetonitrile, 25 oCHO 98% HO OMe OMe
  5. 5. CATALYTIC CYCLE OF THE REDUCTION REACTION O CO2Et RCOO Pd (II) NHBoc RCOOH H Pd (0) RCOO O Pd CO2Et H Zn (II) NHBoc Zn (0) Pd(O2CR)2 O CO2Et O NHBoc (RCO2)Pd CO2Et H NHBoc RCOOHMasesane I. B.; Steel P. G. Bulletin of the Chemical Society of Ethiopia, 2005, vol. 19 (1): 149-152.
  6. 6. ENATIOSELECTIVE VERSION PdCl2, Zn, CO2H Chiral organic acid CO2H CO2H Solvent, 25oC, 16 h +Entry Solvent Acid Conversion Yield (%) [α]D ee (%) (C,1; CHCl3) (%)1 CH3CN L(+)-Mandelic acid 79 42 +28.5 98 CH3CN/ L (+)-Mandelic acid 75 32 +18.3 632 H2O (9:1)3 EtOH L (+)-Mandelic acid 80 94 +11.0 374 MeOH L (+)-Mandelic acid 46 88 +16.0 555 Toluene L (+)-Mandelic acid 76 86 +20.0 696 CH3CN CH3CO2H 24 83 0.0 07 CH3CN L(+)Tartaric acid 100 71 +29.0 >99 CH3CN/8 H2O (9:1) L(+)Tartaric acid 100 47 +2.0 09 MeOH L(+)Tartaric acid 45 80 +10.7 3711 CH3CN Proline 70 96 +2.0 912 EtOH Proline 38 72 +2.0 9 Bwire R. N.; Majinda R. R. T.; Masesane I. B. 2007; Bull. Chem. Soc. Ethiop. 21(3), 457-460.
  7. 7. BEST SYNTHESIS DISCUSSION FORUM http://totallysynthetic.com/blog/………..An intriguing paper has been publishedin JACS by Xinbo Wang, Bo Zhang and David Zhigang Wang.In this, they suggest it is possible to oxidise benzylic alcohols to the correspondingketones using sodium hydride (amongst other chemistry).Given that sodium hydride is, well, a hydride – this is quite something. Does it work?Hard to say without giving it a go, so I am. We had this gear in the lab, so I’m giving it a go.10.30 – Toothe dried flask out from the oven, flushed it with nitrogen andvacuum. Added (dry) THF, and cooled with ice water.Also, found the big ice scoop I’ve been looking for ages on the biology floor. Thieving bastards…
  8. 8. SYNTHETIC APPROACHES TO CYCLIC β-AMINO ACID DERIVATIVES CO2Et 1. Amine/H+ CO2Et 2. Reduction1. REDUCTIVE AMINATION O NHR CO2Et R R CO2Et N Li2. MICHAEL ADDITION NRR 1. NaN3 CO 2Et 2. Curtis CO 2Et 3. CURTIS REARRANGEMENT Rearrangement CO 2H NHR Park, K.-H.; Kurth, M. J. Tetrahedron 2002, 58, 8629-8659. Fülöp, F. Chem. Rev. 2001, 101, 2181-2204. Liu, M.; Sibi, M. P. Tetrahedron 2002, 58, 7991-8035.
  9. 9. OUR OXANORBORNYL APPROACHES TO CYCLIC β-AMINO ACID DERIVATIVES 1. Diels-Alder reaction of furan and (E)-ethyl 3-nitroacrylate O O CO2Et AcO CO2EtO2N CO2Et NO2 AcO NHBoc OAc 2. Diels-Alder reaction of furan and maleic anhydride OAc O O O O AcO CO2Me O O AcO NHCO2Me O O OAc
  10. 10. D-A REACTION OF ETHYL (E)-3-NITROACRYLATE AND FURAN I i I2, N2O4, Et2O, 91% O2N Pr2NEt, Et2O, 84% O2N CO 2Et CO 2Et CO 2Et I IO2N H H NO 2 H CO 2Et H CO 2Et H H O 1. Zn, HCl, EtOH O Favoured 2. iPr2NEt, (Boc)2O NO2 77% NHBoc CO2Et CO2Et Furan, solvent CO2Et O O2N Temp. O CO2Et CO2Et NO2 NHBoc Solvent/Temp.(oC) CHCl3/25 CHCl3/-20 Neat/25 MeOH/25 Toluene/80 CH3CN/25 Endo/Exo ratio 2:1 4:1 3:1 2:1 2:1 2:1 McMurry, J., E.; Musser, J., H. Organic syntheses 1977, 56, 65-68.
  11. 11. COMPOUNDS WE PREPARED FROM THE OXANORBORNYL β-AMINO ACID OH NH2 CO2Et O NHBoc O CO2H OH O CO2Et NHBoc CO2EtAcO CO2Et AcO NHBocAcO NHBoc OAc OAc
  12. 12. BASE-MEDIATED ELIMINATION OF THE OXYGEN BRIDGEO EtO2C CO 2Et CO2Et KHMDS, THF, -50oC, 71% H BocHN NHBoc OH OH Elimination of the carbamate give (H3C)3Si N Side product. Si(CH3)3 O CO2Et NHBoc
  13. 13. TOWARDS TRIHYDROXYCYCLOHEXYL β-AMINO ACIDS CO2Et MCPBA, NaHCO3, CH2Cl2 CO2Et CO2Et 77% O +O NHBoc NHBoc NHBoc OH OH OH Selectivity 9 : 1 1. HClO4, H2O/Acetone 2. Ac2O, pyridineAcO CO2Et AcO CO2Et Pd/C, EtOH 98% H HAcO NHAc AcO NHAc H AcO CO 2Et OAc OAc AcO NHA c OAc H H Selected NOESY interactions
  14. 14. TOWARDS TRIHYDROXYCYCLOHEXYL β-AMINO ACIDS CO2Et MCPBA, NaHCO3, CH3CN CO2Et CO2Et 63% O + O NHBoc NHBoc NHBoc OH OH OH 1. HClO4, H2O/Acetone Selectivity 6:4 2. Ac2O, pyridine, 73%AcO CO2Et AcO CO2Et Pd/C, EtOH 98%AcO NHAc AcO NHAc OAc H OAc H OAc CO 2Et H NHA c O Ph OAc O OAc O Selected NOESY interaction H3C NH
  15. 15. TYPICAL NMR SPECTRA CO2Et AcO AcO AcO CO 2Et NHB oc AcO NHAc AcO OAc CO2Et OAc AcO CO 2Et AcO NHAc NHB oc AcO OAc OAc
  16. 16. DIELS-ALDER REACTION OF FURAN AND MALEIC ANHYDRIDE O O O O CO2Me o O 25 C, 98% MeOH, 25oC O + O CO2H 87% O O CURTIS REARRANGEMENT OO ClCO2Me, O CO2Me CO2Me NEt3, THF CO2Me Toluene, 50 oC CO2H then NaN3, CON3 then CH3OH, NHCO2CH3 H2O, 0 oC, 25 oC, 63% from the acid Chola J.; Masesane I. B. Tetrahedron Letter 2008, vol. 49, 5680-5682
  17. 17. LEWIS ACID MEDIATED OPENING OF BICYCLIC β-AMINO ACID AND SYN-DIHYDROXYLATION OAc O BF3.Et2O, Ac2O, CO2Me CO2Me 0 oC, 61%, NHCO2CH3 NHCO2Me OAc i. OsO4, Me3NO.H2O, H H H R acetone R ii. Ac2O, py, CO2Me H 76% from the H R R NHCO2Me alkene R = OAc OAc Selected NOESY interactions AcO CO2Me AcO NHCO2Me OAc Chola J.; Masesane I. B. Tetrahedron Letter 2008, vol. 49, 5680-5682
  18. 18. ANTI-DIHYDROXYLATION THROUGH EPOXIDATION OAc OAc OAc MCPBA, CO2Me CO2Me CO2Me CH2Cl2, O + O 25 oC NHCO2Me NHCO2Me NHCO2Me OAc OAc OAc 90:10 OAc OAc CO2Me AcO CO2Me HClO4, O H2O/acetone NHCO2Me Ac2O, pyridine, AcO NHAc OAc 64% from epoxide OAc H H R H R R CO2Me H R H NHAc R = OAc Selected NOESY interactionsChola J.; Masesane I. B. Tetrahedron Letter 2008, vol. 49, 5680-5682.
  19. 19. http://www.scirus.com/ is the most comprehensive scientific research tool on the web. With over 370million scientific items indexed at last count, it allows researchers to search for notonly journal content but also scientists homepages, courseware, pre-print servermaterial, patents and institutional repository and website information. Some of the Information Sources
  20. 20. BACKGROUND TO CYCLODIMERIZATION OF STYRENE OXIDES O O O CHO OH H3PO4 + OH O R R H3PO4 R R O O O O ORR R
  21. 21. CYLODIMERIZATION OF STYRENE OXIDES
  22. 22. CYCLODIMERIZATION OF STYRENE OXIDE mCPBA, CH2Cl2, O NaHCO3, 25 oC, 88% H3PO4, 25 oC 61% O O + O O 75:25Mazimba, O.; Majinda, R. R.; Masesane, I. B. Tetrahedron Letters 2009, vol. 50, 5927-5929
  23. 23. CYCLODIMERIZATION OF CHLOROSTYRENE OXIDES O Cl Cl H3PO4, 25 oC O O 72% + Cl O O Cl Cl 75:25 O Cl Cl H3PO4, 25 oC O O 62% + Cl O Cl O Cl 75:25 Cl O H3PO4, O 25 oC, 65% Cl O ClMazimba, O.; Majinda, R. R.; Masesane, I. B. Tetrahedron Letters 2009, vol. 50, 5927-5929
  24. 24. POSSIBLE MECHANISM OF THE CYCLODIMERIZATION REACTION H Ph Ph O H O O OPh OH Ph O Ph OH Ph Ph 1,2-hydride shift Ph Ph Ph O O cyclisation O O OH OH Ph Ph Ph Mazimba, O.; Majinda, R. R.; Masesane, I. B. Tetrahedron Letters 2009, vol. 50, 5927-5929
  25. 25. CYCLODIMERIZATION OF METHYLSTYRENE OXIDE Me O O o H3PO4, 25 C 81% OMe Me O O o Me H3PO4, 25 C Me 82% O Me
  26. 26. CYCLODIMERIZATION OF METHOXYSTYRENES MeO mCPBA, CH2Cl2, O NaHCO3, 25 oC, 85% OMeO OMe MeO mCPBA, CH2Cl2, O NaHCO3, 25 oC, MeO 96% OMeMeO O OMe OMe
  27. 27. ARE WE THERE YET? SUMMARYO cat. PdCl2, Zn, acid, O CO2Et CO2Et acetonitrile, 25 oC, 16 h NHBoc NHBoc R O AcO CO2RO CO2R AcO NHR NHR OAc O H3PO4 O O
  28. 28. ACKNOWLEDGEMENTSResearch associates Financial assistance Dr P. G. Steel  University of BotswanaDr Thota Ganesh University of Durham Dr Darren Orton Royal Society of Chemistry Prof. N. Torto  Academy of Science for the Dr R. Mapitse Developing world (TWAS) Prof. R. Majinda Dr MothankaStudents Reginah Bwire Jushua Chola Dr Musa ChachaOfentse Mazimba Nayang Kgakatsi And thank you for your attention!

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