UNIT-II
ASYMMETIC SYNTHESIS-II
Methodologies in asymmetric synthesis
UNIT– II
Methodologies in asymmetric synthesis Strategies in Asymmetric Synthesis:
l. Chiral substrate controlled, 2. Chiral reagent controlled and 3. Chiral catalyst controlled.
1. Chiral Substrate controlled asymmetric synthesis: Nucleophilic additions to chiral
carbonyl compounds. 1, 2- asymmetric induction, Cram’s rule and Felkin-Anh model.
2. Chiral reagent controlled asymmetric synthesis: Asymmetric reductions using
BINAL-H. Asymmetric hydroboration using IPC2 BH and IPCBH2.
3. Chiral catalyst controlled asymmetric synthesis: Sharpless and Jacobsen
asymmetric epoxidations. Sharpless asymmetric dihydroxylation. Asymmetric
hydrogenations using chiral Wilkinson biphosphine and Noyori catalys. Enzyme mediated
enantioselective synthesis.
Text Books and Reference Books:
1) Organic Synthesis, Christine Willis and Martin Willis, Oxford Chemistry
primers.
2) Principles of Organic Synthesis, ROC Norman and JM Coxon, third
edition, CBS, Publisher, Delhi.
3) Organic Synthesis, M. B. Smith, Mc Graw Hill, International Edition.
4) Organic Chemistry, Clayden, Greeves and Stuwart Warren.
5) Modern Organic Synthesis-an introduction by George S.Zweifel and
Michael H. Nantz, W. H. Freeman & company, New York
Catalytic enantioselective epoxidation of unfunctionalized olefins with chiral (salen)manganese(III)
complexes.
side-on perpendicular approach". The approach is over the diamine bridge, where
the steric bulk of the tert-butyl groups on the periphery of the ligand do not interfere
with the alkene's approach
Preparation
Both enantiomers of Jacobsen's catalyst are commercially available. Jacobsen's
catalyst can be prepared by 1,2-diaminocyclohexane enantiomers with
3,5-di-tert-butyl-2-hydroxybenzaldehyde to form a Schiff base
Reaction with manganese(II) acetate in the presence of air gives the manganese(III)
complex, which may be isolated as the chloro derivative after the addition of
lithium chloride. Shown below is the preparation of the (R,R)-enantiomer.
R Noyori introduced the ruthenium-based catalysts for the asymmetric hydrogenated
polar substrates, such as ketones and aldehydes
Noyori is most famous for asymmetric hydrogenation using as catalysts complexes of rhodium
and ruthenium, particularly those based on the BINAP ligand. Asymmetric hydrogenation of an
alkene in the presence of ((S)-BINAP)Ru(OAc)2 is used for the commercial production of
enantiomerically pure (97% ee) naproxen, used as an anti-inflammatory drug.
The antibacterial agent levofloxacin is manufactured by asymmetric hydrogenation of ketones in
the presence of a Ru(II) BINAP halide complex.
He has also worked on other asymmetric processes. Each year 3000 tonnes of menthol are
produced (in 94% ee) by Takasago International Corporation, using Noyori's method for
isomerisation of allylic amines.[14]
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