Titanium-Catalyzed Reductive Cyclization of δ,ε-Unsaturated Ketones and Aldehydes

摘要

We have reported titanium-catalyzed carbonyl-olefin and carbonyl-alkyne reductive cyclization reactions related to the stoichiometric reactions first reported by Whitby and Hewlett. The cis selectivity of the carbon—carbon bond forming reaction is complimentary to the trans selectivity obtained in related samarium-mediated cyclizations reported by Molander. Both ketones and aldehydes are good substrates for the titanium-catalyzed reductive cyclization reaction. Previously developed reductive cyclization protocols are largely limited to ketone substrates. Reductive coupling reactions of chiral metallocenes should proceed with high levels of asymmetric induction. This idea, however, remains largely untested since the stoichiometric nature of most of the methods reported to date renders asymmetric processes impractical. With the development of a catalytic procedure, a practical asymmetric reductive cyclization reaction can now be envisioned. Efforts to develop such a reaction are currently in progress.