Chiral Proline Derivatives via One-Pot [3+2] Cycloaddition-Cross-Coupling

Significance

In an extension of an enantioselective propargylation reaction of α-imino esters with allenyl(tributyl)stannane developed earlier by this group (H. Kagoshima, T. Uzawa, T. Akiyama Chem. Lett. 2002, 298-299), the use of the same reaction under harsher conditions has been shown to afford chiral proline [3+2] cycloadduct 1. Incipient destannylation, which occurs upon isolation, is overcome by subsequent in situ Stille coupling yielding 4-phenylated dehydroproline esters in low to good yields and good enantioselectivities. In one example, subsequent iododestannylation was performed rapidly using iodine to afford a 4-iodo dehyroproline ester derivative in good yield and enantioselectivity (one recrystallization step yields the product with >99% ee). A mechanism is proposed based on a sequential propargylation-cyclization process in which the enantioselectivity is derived from preferential Si-face attack.