Catalytic Reductive Coupling of Epoxides and Aldehydes: Epoxide-Ring Opening Precedes Carbonyl Reduction


  • Postdoctoral support was provided by the Fonds Québécois de la Recherche sur la Nature et les Technologies (FQRNT, fellowship to C.M.) and Boehringer-Ingelheim (New Investigator Award to T.F.J.). We thank Engelhard-CLAL for a generous donation of [(Ph3P)3RhCl] and the National Institute of General Medical Sciences (GM-063755), the NSF (CAREER CHE-0134704), Amgen, Bristol-Myers Squibb, GlaxoSmithKline, Johnson & Johnson, Merck Research Laboratories, Pfizer, the Sloan Foundation, and MIT for generous financial support. The NSF (CHE-9 809 061 and DBI-9 729 592) and NIH (1S10RR 13886-01) provide partial support for the MIT Department of Chemistry Instrumentation Facility.


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Several lines of evidence suggest that reduction of the carbonyl group occurs after epoxide-ring opening in the first examples of catalytic, reductive coupling of epoxides and aldehydes (see scheme). The hydroxyether products are obtained with >95:5 regioselectivity in all cases, independent of the steric and electronic nature of R1 and R2.