Highly regio- and stereo-selective carbometallation reaction of fluorine-containing internal acetylenes with organocopper reagents

Abstract

The carbometallation reactions of fluoroalkylated internal alkynes with various organocopper reagents derived from organolithium, Grignard, and organozinc reagents were examined. All carbocupration reactions proceeded smoothly in a highly regio- and stereo-selective manner to give the corresponding vinylcopper intermediates. The intermediates reacted with H + smoothly, leading to the trisubstituted alkenes in high to excellent yields, whereas they reacted only with strictly limited carbon electrophiles such as allyl-, crotyl-, methallyl bromide, etc, probably due to the low reactivity exerted by an electron-withdrawing fluoroalkyl group. Treatment of vinylcopper with iodine resulted in a high yield of the corresponding vinyl iodide, which was employed successfully for Suzuki–Miyaura and Sonogashira cross-coupling reactions. In addition, two key reactions, the carbocupration and the Suzuki–Miyaura cross-coupling reaction realized the first highly stereoselective total synthesis of anti-estrogen drug, panomifene.