Stereoselective synthesis of 1,2-disubstituted beta-amino alcohols by nucleophilic addition to N-tert-butanesulfinyl alpha-alkoxyaldimines.
N-tert-Butanesulfinyl alpha-alkoxyaldimines are readily prepared from protected (S)-lactals without epimerization at the alpha-stereocenter. Addition of ethyl and phenyl Grignard reagents, as well as the titanium enolate of methyl acetate, to the N-tert-butanesulfinyl aldimines provides 1,2-disubstituted beta-amino alcohols in good yields (73-98%) and with high diastereoselectivities. Either syn- or anti-amino alcohol products can be obtained by the appropriate choice of alcohol protecting groups and/or reaction conditions. Finally, deprotection of the addition products provides straightforward access to either syn- or anti-1,2-amino alcohols.
Evans
Jared W
JW
Center for New Directions for Organic Synthesis, Department of Chemistry, University of California, Berkeley, California 94720, USA.
Ellman
Jonathan A
JA
D000605:Amino Alcohols / Q000138:chemical synthesis* / Q000737:chemistry; D007097:Imines / Q000737:chemistry*; D008274:Magnesium / Q000737:chemistry; D009942:Organometallic Compounds / Q000737:chemistry; D013237:Stereoisomerism; D013457:Sulfur Compounds / Q000737:chemistry*
D000605:Amino Alcohols; D007097:Imines; D009942:Organometallic Compounds; D013457:Sulfur Compounds; D008274:Magnesium