anti-Selective Direct Catalytic Asymmetric Mannich-type Reaction of Hydroxyketone Providing β-Amino Alcohols

Abstract
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.

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