Asymmetric synthesis of beta-amino alcohols and enantioselective synthesis of chiral sulfinic esters

Chiral non-racemic beta-amino alcohols represent an important class of molecules that are present in a variety of biologically relevant natural products, therapeutics agents, and chiral ligands. As a result of their ubiquitous nature within organic chemistry, a number of useful synthetic methods, both enantioselective and diastereoselective, have been devised for their preparation. Among these methods, the addition of organometallic reagents into alpha-alkoxy imines represents a potentially versatile and convergent entry. However, only a few methods have been reported utilizing this approach.; N-tert-Butanesulfinamide has been extensively developed as a chiral ammonia equivalent not only by the Ellman group but also by a variety of other researchers. Of particular importance, is the application of this technology to the synthesis of alpha-branched amines, which can be obtained with exceptional levels of diastereofacial selectivity. Chapter 1 of this dissertation will discuss the extension of sulfinamide methodology to the synthesis of 1,2 disubstituted beta-amino alcohols by the addition of organometallic reagents into alpha-alkoxy N-sulfinyl imines.; In addition to the synthetic utility of N-tert-butanesulfinamide, its use is made all the more palatable by its rapid and straightforward synthesis through the enantioselective oxidation of tert-butyl disulfide. While this process is exceptionally efficient, its widespread application to other derivatives has not yet been realized. This is due to the limitations of the crystallinity and the configurational and chemical stability of the intermediate thiosulfinate esters.; Sulfinate esters are similar to thiosulfinate esters in that they both function as useful chiral, non-racemic precursors to both sulfoxides and sulfinamides. However, sulfinate esters do not have the same configurational and chemical instabilities observed for thiosulfinate esters. A brief overview of both diastereoselective and enantioselective methods for the asymmetric synthesis of sulfinate esters developed by other authors is given in Chapter 2. Chapter 3 describes how we developed the first example of a catalytic enantioselective synthesis of sulfinate esters through dynamic resolution of racemic tert-butanesulfinyl chloride, and Chapter 4 describes the use of chiral tertiary aliphatic amines as efficient sulfinyl transfer catalysts. With more development, the synthesis of sulfinic acid derivatives through sulfinyl transfer could represent a significant advancement in the preparation of this class of molecules.