Enantioselective carbon-carbon bond forming reactions catalyzed by chiral nickel (II) complexes

Abstract

Over the past decades, the construction of new carbon-carbon bonds has been of great importance in the synthesis of organic products, such as in the pharmaceutical industry. The significance of this synthesis lies in the control of stereoisomerism, which has been made possible through the use of chiral auxiliaries, such as 1,3-oxazolidin-2-ones, also known as Evans auxiliaries. This methodology provides good yield and stereochemical control but requires stoichiometric amounts of the chiral auxiliary and involves multiple steps. The need for more efficient conditions has opened up the possibility of synthesizing direct reactions using catalysts. A few years ago, our group developed a new method based on the reaction of chiral nickel(II) complexes as catalysts and N-acyl-1,3-thiazinane-2-thiones as platforms for nucleophilic enolates. Initially, this method involved the construction of a single stereocenter using electrophiles from an activated oxacarbenium cation generated in the reaction mixture. Currently, the group is working on the expansion of such a method for the simultaneous installation of two stereocenters using nickel(II) complexes and similar nucleophilic partners. With all the aforementioned points, this project aims to synthesize the scaffolds 1,3-oxazinane-2-thione and 1,3-oxazolidine-2-thione on a large scale for their subsequent acylation with carboxylic acids and acyl chlorides. The products obtained from acylation will be used in direct aldol reactions, employing both chiral and achiral nickel(II) complexes to observe their potential effect on conversion and enantioselectivity.