Titanium-mediated cross-coupling of substituted alkenes with imines for the synthesis of 1,5-amino alcohols and homoallylic amines

We have aimed to develop general synthetic strategies for regio- and stereoselective carbon--carbon (C--C) bond formation through convergent coupling of pi-systems. While metal---it complexes possess suitable reactivity for such C--C bond construction, methods for bimolecular functionalization of unactivated pi-systems are significantly underdeveloped due to difficulties associated with the low reactivity as well as the control of regio- and stereoselectivity. Our efforts focused on exploring the potential of titanium-mediated coupling as a general strategy to accomplish selective functionalization of unactivated alkenes are described. We have developed a regio- and stereoselective cross-coupling reaction of unactivated, substituted alkenes with imines. This process enables convergent access to stereodefined 1,5-amino alcohols and substituted piperidines from stereochemically simple starting materials. In addition, we have defined a new class of stereoselective imine allylation reactions that proceeds via alkoxide-directed cross-coupling between allylic alcohols and imines. The net transformation is a formal allyl transfer that does not require the intermediacy of allylic organometallic reagents and provides a convenient pathway to highly functionalized homoallylic amines. Overall, our studies have resulted in the discovery of new regio- and stereoselective processes for convergent C--C bond formation between imines and substituted alkenes. These methods have expanded the utility of titanium-mediated coupling in the preparation of highly functionalized nitrogen-containing compounds relevant to the synthesis of biologically important molecules.