Cross-Coupling of Grignard Reagents with Sulfonyl-Activated sp3 Carbon-Nitrogen Bonds

Sulfonyl-activated sp(3) carbon-nitrogen bonds have been found to be cleaved by Grignard reagents in the presence of 5 mol% of copper(I) iodide (CuI). Significantly, a broad range of sulfonyl-activated benzylic, allylic, and propargylic amines smoothly undergo the cross-coupling reaction with Grignard reagents to afford structurally diverse coupling products in good to excellent yields and with high chemo-, regio-, and stereoselectivity. Moreover, an S(N)2 mechanism has been demonstrated to be involved in the cross-coupling reaction that allows the asymmetric synthesis of chiral hydrocarbons from optically active alpha-branched amine derivatives.