3. II. Carbon-carbon bond formation via nucleophilic
attack on a ligand.
ORGANOMET CHEM IN ORGANIC SYNTHESIS
4. III. Carbon-carbon bond formation via carbonyl or
alkene insertion.
ORGANOMET CHEM IN ORGANIC SYNTHESIS
5. IV. Carbon-carbon bond formation via transmetallation
reactions.
ORGANOMET CHEM IN ORGANIC SYNTHESIS
6. V. Carbon-carbon bond formation through cyclization
reactions.
ORGANOMET CHEM IN ORGANIC SYNTHESIS
7. The C=C and C=O undergoes transformations to variety of
organic compounds (alcohols, alkyl halides, alkanes).
The C=C and C=O are planar and achiral but in their reactions
creates one or more stereogenic centers in the reaction product.
Assymetric Hydrogenations
8. Methods of producing an enantiomer of a chiral
compound:
Chemical resolution of a racemate
Chiral chromatography
Use of a chiral natural products as starting material
Stoichiometric use of chiral auxilliaries
Asymmetric catalysis
Asymmetric Hydrogenations
9. Chiral chromatography:
- Use of chiral, enantioenriched groups to the solid
support
- In the chiral environment, the two enantiomers will
have diastereomerically different interactions with the
columns
ORGANOMET CHEM IN ORGANIC SYNTHESIS
10. Synthesis of biotin (involved in enzymatic transfer of
CO2):
ORGANOMET CHEM IN ORGANIC SYNTHESIS
11. Use of chiral auxiliaries:
ORGANOMET CHEM IN ORGANIC SYNTHESIS
12. Asymmetric Catalysis: same approach as the use of
chiral auxilliary except that the selectivity occurs
catalytically
The most environmentally benign approach to
enantioselectivity.
ORGANOMET CHEM IN ORGANIC SYNTHESIS
38. CARBON – CARBON BOND FORMATION VIA
NUCLEOPHILIC ATTACK ON AN 3 - ligand:
THE TSUJI-TROST REACTION
ORGANOMET CHEM IN ORGANIC SYNTHESIS
39.
40. TSUJI – TROST REACTION
Organic synthesis using allylic substrates:
unpredictable stereochemistry
poor control of regioselectivity
possible carbon- skeleton rearrangement.
Leaving groups for Tsuji-Trost Reaction
41. Tsuji-Trost Reaction:
With hard nucleophiles (pKa of conjugate acid >25)
results in an overall inversion of configuration at the
allylic site.
With soft nucleophile (pKa of conjugate acid < 25) react
to give retention of configuaration.
46. Several points in catalytic cycle where asymmetric
reaction could occur:
a) enantiomeric faces of the alkene
b) enantiomeric leaving groups
c) enantioface exchange in the 3 allyl complex
d) attack at enantiotopic termini of the 3 ally
ligand
e) Attack by different enantifaces of prochiral
nucleophiles.
ASSYMETRIC TSUJI – TROST REACTION
57. Heck Reaction – migratory C=C insertion
Step a ) OA
b) alkene coordination
c) migratory insertion of C=C
d) -elimination
Insertion is key step
R = aryl, alkyl, benzyl or allyl
X = Cl, Br, I, OTf
58. Rate of reaction and regioselectivity are sensitive to
steric hindrance about the C=C bond.
Rate of reaction varies according to:
Heck Reaction:
62. Also know as Cross Coupling Reaction:
C-C Bond Bond formation via Transmetallation Reactions
63. Transmetallation Reaction
Transmetallation Reaction – a method for introducing a -bonded hydrocarbon ligands
Into the coordination sphere transition metals.
The equilibrium is thermodynamically favorable from left to right if the
electronegativity of M is greater than that of M’.
77. Synthesis Application: The chemo-, regio-, and
stereoselectivity similar to those with Stille. Suzuki more
widely used for aryl-aryl coupling.
CROSS-COUPLING REACTION - SUZUKI
78. Cross coupling between alkynyl and aryl :
CROSS-COUPLING REACTION - Sonogashira
- Requires high loadings of Cu and Pd catalysts, relativelly hight
temperatures
- Cu-alkynes are formed in situ and then the alkyne is transferred
to Pd.
