Asymmetric syntheses of amines using N-sulfinyl metalloenamines

N-tert-Butanesulfinyl imines are exceedingly versatile intermediates for the asymmetric synthesis of a wide variety of amines because of a number of ideal features associated with this structure. One of the effective methods to prepare enantiomerically enriched amines is nucleophilic additions to N-tert-butanesulfinyl imines. In Chapter 1, an overview of the progress made in the asymmetric synthesis of amines by nucleophilic additions to N-tert-butanesulfinyl imines is described. This method is applicable to the preparation of diverse classes of alpha-chiral amines, and the generality of this chemistry has rapidly led to the extensive use of N-tert-butanesulfinyl imines in both academics and industry.; Another general way to form stereocenters using imines is metalloenamine addition to electrophiles. However, use of metalloenamines derived from N-sulfinyl imines has not previously been reported. In Chapter 2, a general method for the asymmetric synthesis of both syn- and anti-1,3-amino alcohols is presented. The highly diastereoselective addition to aldehydes is developed as the first application of metalloenamines derived from N-sulfinyl imines. The reduction of the product beta-hydroxy N-sulfinyl imines with catecholborane and LiBHEt3 provides syn- and anti-1,3-amino alcohols in high yields with very high diastereomeric ratios. The application of this method to the convergent and efficient asymmetric syntheses of the two natural products, (-)-8-epihalosaline and (-)-halosaline, is also presented. In Chapter 3, highly diastereoselective alpha-alkylation of N '-tert-butanesulfinyl amidines is described along with methods for converting the alkylation products to N-sulfinyl aldimines and ketimines, which are versatile precursors for enantiomerically enriched amines. This method should provide for the efficient synthesis of a wide variety of chiral amines incorporating both (alpha- and beta-stereocenters. In Chapter 4, application of this method to the first enantioselective total synthesis of (6R, 7S)-7-amino-7,8-dihydro-alpha-bisabolene is presented.