anti-Selective direct catalytic asymmetric Mannich-type reaction of hydroxyketone providing beta-amino alcohols.
An anti-selective direct catalytic asymmetric Mannich-type reaction is described. The Et(2)Zn/(S,S)-linked-BINOL 1 = 4/1 complex promoted a Mannich-type reaction of 2-hydroxy-2'-methoxyacetophenone (2) and N-diphenylphosphinoyl imines 3. Using as little as 0.25-1 mol % of the catalyst, we obtained Mannich adducts 4 in excellent yield (up to 99%), diastereoselectivity (anti/syn = up to >98/2), and enantiomeric excess (up to >99.5%). The anti-selectivity in the present system is complementary to that observed using previously reported methods, providing a novel efficient method to synthesize anti-beta-amino alcohols in a highly enantioselective manner. Facile deprotection of the N-diphenylphosphinoyl group and commercial availability of both Et(2)Zn solution and (S,S)-linked-BINOL 1 also make the present catalysis practical.
Matsunaga
Shigeki
S
Graduate School of Pharmaceutical Sciences, The University of Tokyo, Hongo, Bunkyo-ku, Tokyo 113-0033, Japan.
Kumagai
Naoya
N
Harada
Shinji
S
Shibasaki
Masakatsu
M
D000438:Alcohols / Q000737:chemistry*; D000605:Amino Alcohols / Q000138:chemical synthesis*; D002384:Catalysis; D018360:Crystallography, X-Ray; D007097:Imines / Q000737:chemistry; D007659:Ketones / Q000737:chemistry*; D009284:Naphthols / Q000737:chemistry; D009942:Organometallic Compounds / Q000737:chemistry; D013237:Stereoisomerism
D000438:Alcohols; D000605:Amino Alcohols; C406944:BINOL, naphthol; D007097:Imines; D007659:Ketones; D009284:Naphthols; D009942:Organometallic Compounds; C454811:diethylzinc