Asymmetric reaction is a very important class of reactions in organic chemistry
where a new bond is created in an enantiocontrolled manner. The elegant and
economically most attractive way to introduce chirality in a chemical reaction
is by using a catalytic amount of chiral controller. The search for asymmetric
catalysts that provide high yields and enantioselectivity is an ongoing quest
for organic chemists. Current challenges focus on the development of enantioselective
catalysts with high activity and broad substrate generality directed towards
efficient and environment friendly methods for the synthesis of enantiopure
compounds. There have been significant advances in the field of homogeneous
asymmetric catalysis, which culminated in the award in 2001 of the Nobel
Prize for Chemistry to Noyori, Sharpless and Knowles for their contributions
to homogeneous asymmetric hydrogenation and oxidation.
The present inventors
have found that chiral catalysts derived from bis-homocubane (BHC) would
be superior to the existing class of catalysts for the following
reasons:
(a) The proposed BHC-ligands are bidendate ligands with C1 symmetry; (b)
Some of them are expected to chelate well with metal complexes; (c) The
cage backbone will provide enough rigidity to bring selectivity in reactions;
(d) The BHC moiety enhances the lipophilicity of the ligand, which could
lead to more effective recycling of the ligand; (e) The source of chirality
will be chiral cage backbone with 8 fixed chiral centers which can be obtained
by photocyclization of dicyclopentadiene dicarboxylate or dicyclopentadienone
followed by simple transformations; (f) since all the chiral centers are
fixed/rigid, catalyst remains extremely stable, i.e. racemization doesn’t
take place; (g) Since both the enantiomers of the catalyst are obtained after
resolution, there is scope for synthesizing both the enantiomers of the product
separately and stereoselectively.
The enantiomers of a polycyclic cage diol have been resolved via conversion
to their diastereomers, separation of the diastereomers and hydrolysis. The
enantiopure cage diol was employed as catalyst in the addition of phosphonates
to activated imines (Mannich reaction) to afford the products in high yield
and enantioselectivity. Several bis-homocubyl systems possessing functional
groups such as hydroxyl, amino, azido, phosphonate/phosphate, imidazolyl,
triazolyl, oxazolyl, nitrite, nitrile, tetrazole, nitro, carboxylate and
keto have been synthesized for their application as ligands and organocatalysts
in various asymmetric reactions.
Indian patent application no. 98/MUM/2008 Patent grant no.
Inventors: Irishi N N Namboothiri
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