Last few decades have seen development of chiral catalysis to an extent
where it can be thought of biomimicking. However, source of pure enantiomer
still beholds in the technique of classic resolution, biochemical and biological
methods. This is due to the fact that most of the asymmetric reactions are
not absolute in the sense of selectivity. The present invention envisages
that the autocatalytic amplification can be critical leading to the utilization
of general reactions where enantiomeric excess is anything but absolute.
The exclusion of external ligand for catalysis save costs to a great extent
and also removes the necessity to separate the product from catalyst which
could further prove economical in commercial applications.
The main disadvantage with the prior art is that the projected speculations
for these reactions in the absence of catalyst require three steps to attain
such enantioselectivities. The existing process for preparation of aminophosphonates
requires addition of other chiral catalysts such as cinchonine [Tetrahedron:Asymmetry,2007,doi:10.1016/j.tetasy.2007.11.001].
Such types of processes are cumbersome and costly.
Thus, there is a need for development in terms of a process for preparation
of nitrophosphonates, more particularly, γ-nitrophosphonates which would
be first and cost effective.
The present inventors have found a process which by adopting selectively
asymmetric autocatalysis, mirror symmetry breaking and absolute asymmetric
synthesis in Michael addition produces an amplification of greater than 99%
enantiomeric excess (ee) in one step which is about three times superior
to that of Soai reaction in literature. The products synthesized and their
derivatives are possible drug candidates and their asymmetric synthesis was
Indian patent application no. 2359/MUM/2007 Patent grant no.
Inventors: Irishi N N Namboothiri and Vishal Rai