CARBON-NITROGEN DOUBLE BOND STEREOSELECTIVE REDUCTION

Abstract

The carbon-nitrogen double bond reduction represents a powerful and widely used transformation that allows to generate a new nitrogen-bearing stereocenter. Since chiral amino groups are ubiquitous in a variety of bioactive molecules, the development of a catalytic stereoselective process for the preparation of enantiomerically enriched amines by imine reduction is attracting increasing interest. Recently great efforts have been made to develop efficient organocatalytic methods to perform enantioselective imine reductions and reductive amination processes. In particular, research has focused on trichlorosilane-mediated reductions due to the possibility of generating chiral catalysts for imine reduction simply by coordination of HSiCl3 with a chiral Lewis base. This work reports the design and synthesis of new catalytic systems for the reduction of C=N double bond as well as the exploration of new synthetic applications. A set of enantiomerically pure Lewis bases containing different diphenyl phosphinyl oxide groups and proline-based catalysts were developed and successfully used in the trichlorosilane-mediated reduction. A highly stereoselective of N-benzyl enamines was also developed, leading to the synthesis of enantiomerically pure lactams. Preliminary experiments allowed to obtain for the first time 1,2,3,4-tetrahydroquinolines via reductive amination with good levels of enantioselection, paving the way for further improvements.