Studies directed toward stereoselective synthesis of 1,3-amino alcohols via intramolecular amidomercuration

Typescript (photocopy).The cyclization of the benzyl carbamate of 6-hepten-2-amine (31) with mercuric trifluoroacetate in nitromethane over a period of 20 h afforded, after borohydride reduction of the organomercurial, the benzyl carbamate of 2,6-dimethylpiperidine (30a) predominantly (98:2) as the cis diastereomer. Cyclization of 31 with mercuric acetate under similar conditions led to non-stereoselective (60:40 trans:cis) formation of 30a. The kinetically controlled product ratio of 95:5 trans:cis, obtained by cyclization of the benzyl carbamate of 5- hexen-2-amine (37) with mercuric trifluoroacetate for 15 min, was equilibrated, after 9 days of stirring, to a 40:60 trans:cis diastereomeric ratio of the 2,5-dimethylpyrrolidine carbamate. Cyclization precursor 31 was synthesized from 4-bromo-1-butene and ethyl acetoacetate in 5 steps with a 65% overall yield. The benzyl carbamate of 4,6-dimethyltetrahydro-1,3-oxazine (28) was formed by treatment of N-(benzyloxycarbonyl)aminomethyl 4-penten2-yl ether (27) with mercuric trifluoroacetate in a 40% yield or in a 60% yield with anhydrous mercuric nitrate in ethyl acetate after 15 min. A 73:27 cis:trans diastereomeric mixture was obtained. The organomercurial intermediate was equilibrated to a 6:94 cis:trans mixture after 46 h with mercuric nitrate in acetone. Cyclization precursor (27) was formed in two steps from benzyl carbamate in a 51% overall yield. The organomercurial formed from 31 was reduced in the presence of acrylonitrile with sodium borohydride to afford the alkylation product 89 in a 46% yield. Sodium borohydride reduction of the organomercurial from 27 with acrylonitrile led to a 32% yield of alkylation product 91. Reductive alkylation of the mercurial from 27 with - chloroacrylonitrile afforded the corresponding alkylation product (93) in a 16% yield