Alpha-(N-carbamoyl)alkylcuprate chemistry in the synthesis of nitrogen heterocycles.
The conjugate adducts obtained via coupling of alpha-(N-carbamoyl)alkylcuprates with alpha,beta-ynoates, alpha-allenyl esters, or alpha.beta-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 alpha/beta-ynoates; pyrrolidin-2-ones, pyrrolizidin-2-ones, and indolizidin-2-ones via alpha,beta-enoates or alpha.beta-enimides. The reluctance of gamma-carbamoyl-alpha,beta-enoates to undergo E/Z isomerization requires the use of (Z)-beta-iodo-alpha,beta-enoates readily prepared by the addition of HI to the alkynyl esters for the efficient preparation of pyrrolinones, tetrahydropyrrolizinones, and tetrahydroindolizinones. Utilization of omega-functionalized alpha,eta-ynoates or beta-iodo-alpha,beta-enoates allows for cyclization onto the omega-functionality providing for a synthetic route to quinolizidines.
Dieter
R Karl
RK
Howard L. Hunter Chemistry Laboratory, Clemson University, Clemson, South Carolina 29634-0973, USA. dieterr@clemson.edu
Lu
Kai
K
D003300:Copper / Q000737:chemistry*; D006571:Heterocyclic Compounds / Q000138:chemical synthesis* / Q000737:chemistry; D015394:Molecular Structure; D009584:Nitrogen / Q000737:chemistry*; D013057:Spectrum Analysis
D006571:Heterocyclic Compounds; D003300:Copper; D009584:Nitrogen