An advance on exploring N-tert-butanesulfinyl imines in asymmetric synthesis of chiral amines.Acc Chem Res. 2008 Jul; 41(7):831-40.AC
Although catalytic asymmetric synthesis has undergone tremendous growth in the last 30 years, chiral auxiliary-aided asymmetric synthesis continues to attract considerable attention. Chiral N- tert-butanesulfinamide, as pioneered by Ellman and co-workers, is undoubtedly one of the most efficient auxiliaries developed to date; it allows the preparation, through simple conversion, of a diverse range of enantiopure amines, which are ubiquitous in natural products and biologically active molecules. Following on from our studies of the SmI(2)-mediated asymmetric syntheses of alpha,gamma-substituted gamma-butyrolactones, we found that simple homocoupling of chiral N- tert-butanesulfinyl imines in the presence of SmI(2) produced enantiopure vicinal C2-symmetric diamines in high yield. In addition, C2-unsymmetric chiral diamines are readily prepared through SmI(2)-mediated cross-couplings of N- tert-butanesulfinyl imines and nitrones; these transformations represented the first successful examples of asymmetric cross-coupling between two different imine species. Subsequently, we discovered another useful reaction induced by SmI(2), the efficient cross-coupling of N- tert-butanesulfinyl imines and aldehydes, which provides ready access to enantiopure anti-1,2-amino alcohols. The synthetic applicability of this reaction was demonstrated through its use in the facile total syntheses of (3R,4S)-statine, d- erythro-sphinganine, (+)-CP-99,994, and (+)-L-733,060. The Zn/In-mediated allylation of chiral N- tert-butanesulfinyl imines yields homoallylic amines. After pondering the reaction mechanism, we developed optimal reaction conditions for reversing the stereogenic outcome, thereby allowing the preparation of enantiopure homoallylic amines of either handedness from single enantiomers of the (R)- or (S)-sulfinyl imine. When a benzoyl-substituted allyl bromide is used for allylation, the reaction proceeds smoothly to give 2-vinyl-substituted anti-1,2-amino alcohols in high yields and diastereoselectivities, another simple method for preparing enantiopure amino alcohols. We employed these reactions in the syntheses of enantiopure allylglycine, 3-allyl-isoindolinones, and (-)-cytoxazone. Further studies led to the discovery that the allylations of N- tert-butanesulfinyl aldimines can be performed in water. The reactions described in this Account are among the simplest and most efficient synthetic methods available for preparing enantio-enriched diamines, amino alcohols, homoallylic amines, and other amine derivatives. These reactions are additionally attractive because of the ready availability of the starting materials, the simplicity of the reaction conditions, and the high degree of stereochemical control. Their applications in the total syntheses of several biologically interesting molecules illustrate the versatility of these transformations; we hope that they will stimulate the development of new synthetic methods.
