Synthesis of 3-Aminoindolizines via Pd/Cu-Catalyzed Reactions

Significance

An interesting annulation methodology for the preparation of 3-aminoindolizidines is reported. Combining readily available heteroaryl bromides with propargyl amines under Pd/Cu catalysis provides a series of aminoindolizidines in modest to excellent yields. A variety of N,N-dialkyl, -diaryl and functionalized propargyl amines are tolerated and the reaction proceeds under low catalyst loading and at low temperatures. The proposed mechanism involves isomerization of the propargyl amine to an allenic intermediate which, driven by copper coordination, undergoes cyclization to give the indolizidine. The proposed heterocylic propargyl amine intermediates were not isolated.