NEW STEREOSELECTIVE SYNTHESIS OF (+-)-trans-2-BUTYL-5-HEPTYL-1-METHYLPYRROLIDINE,ANT VENOM ALKALOID,BY AMINYL RADICAL CYCLIZATION

摘要

New synthsis of (+-)-trans-2-butyl-5-heptyl-1-methylpyrrolidine (1),ant venom alkaloid ,was achieved by the use of stereoselective cyclization of aminyl radicals.Thus ,orthoester Claisen rearrangement of 1-hexen-3-ol(2)gave (E)-ethyl 4-octenoate (3) .Reaction of ester (3) with 2-methylaminopyridine and ALCl_3 afforded the corresponding N-methyl-N(2-pyridyl)amide (4),which was treated with heptylmagnesium iodide at -78degC to give (E)-4-pentadecen-8-one (5).Reductive amination of ketone (5) with methylamine gave N-methyl-1-heptyl-4-octenylamine (6).Treatment of amine (6) with NCS in toluene gave the corresponding N-chloroamine (12),and successive heating under reflux with Bu_3SnH and AIBN resulted in stereoselective cycliZtion of the aminyl radical to give (+-)-trans-2-butyl-5-heptyl-1-methylpyrrolidine (1) in a 59% yield.Similarly,1-nonen-3-ol(7) was converted into N-methyl-1-butyl-4-undecenylamine(11),which was subjecte to the aminyl radical cyclization to give 1 in a 49% yield.