Catalytic asymmetric synthesis of optically active alkynyl alcohols by enantioselective alkynylation of aldehydes and by enantioselective alkylation of alkynyl aldehydes

Abstract

Catalytic asymmetric synthesis of optically active secondary alkynyl alcohols (1) by enantioselective addition of organozinc reagents to aldehydes in the presence of a small amount of catalyst was examined. Enantioselective alkynylation of benzaldehyde by alkynylzinc reagents using (1S,2R)-(–)-N,N-dibutylnorephedrine (2c) as a chiral catalyst gave (1) in moderate enantiomeric excess (e.e.). On the other hand, enantioselective addition of dialkylzinc reagents to alkynyl aldehydes using (S)-(+)-(1-methylpyrrolidin-2-yl)diphenylmethanol (3) as a chiral catalyst afforded (1) in high e.e. The reaction of 3-trimethylsilylprop-2-ynal with diethylzinc in toluene at –20 °C using (S)-(+)-(3)(5 mol%) afforded (–)-1-trimethylsilylpent-1-yn-3-ol in 78% e.e. (S)-(–)-Oct-1-yn-3-ol (6)(precursor of the prostaglandin side chain) was also synthesized in 69% e.e. by employing dipentylzinc.