Chiral phosphoramidites have been identified as excellent ligands for various metal-catalyzed enantioselective transformations. Taking advantage of their easy preparation and modular nature, we designed a fully automated protocol for the parallel preparation of a library of 32 phosphoramidites and its screening in asymmetric hydrogenation of amino acid precursors. This initial study led to the discovery of a new ligand for the preparation of an enantiopure beta(3)-homoalanine precursor. [structure--see text]
An asymmetric hydrogenation process for the α-isopropyl
dihydrocinnamic acid derivative 2, an intermediate for the renin
inhibitor aliskiren (4), has been developed using a rhodium
catalyst ligated with a chiral monodentate phosphoramidite and
a nonchiral phosphine. Whereas catalysts based on two equivalents of monodentate phosphoramidites gave promising results,
the rate of hydrogenation and ee of the product could be
improved spectacularly by the addition of monodentate nonchiral triarylphosphines to these catalysts. This remarkable
mixed-ligand catalyst has been identified using high-throughput
experimentation. With the best catalysts turnover numbers
>5000 mol mol-1, turnover frequencies >1000 mol mol-1 h-1,
and ee's up to 95% have been achieved.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.