α-(N-Carbamoyl)alkylcuprate Chemistry in the Synthesis of Nitrogen Heterocycles

Abstract

The conjugate adducts obtained via coupling of α-(N-carbamoyl)alkylcuprates with α,β-ynoates, α-allenyl esters, or α,β-enoates or enimides undergo N-Boc deprotection and cyclization onto the ester functionality upon treatment with PhOH/TMSCl, catecholboron bromide, or trimethylsilyl triflate. This two-pot sequence provides synthetic routes to 4-alkylidinepyrrolidine-2-ones, 4-alkylidinepyrrolizidin-2-ones, and 4-alkylidineindolizidin-2-ones via allenyl esters; pyrrolin-2-ones, tetrahydropyrrolizin-2-ones, and tetrahydroindolizin-2-ones via α,β-ynoates; pyrrolidin-2-ones, pyrrolizidin-2-ones, and indolizidin-2-ones via α,β-enoates or α,β-enimides. The reluctance of γ-carbamoyl-α,β-enoates to undergo E/Z isomerization requires the use of (Z)-β-iodo-α,β-enoates readily prepared by the addition of HI to the alkynyl esters for the efficient preparation of pyrrolinones, tetrahydropyrrolizinones, and tetrahydroindolizinones. Utilization of ω-functionalized α,β-ynoates or β-iodo-α,β-enoates allows for cyclization onto the ω-functionality providing for a synthetic route to quinolizidines.