Palladium-catalyzed synthesis of 2,1'-disubstituted tetrahydrofurans from gamma-hydroxy internal alkenes. Evidence for alkene insertion into a Pd-O bond and stereochemical scrambling via beta-hydride elimination.
Palladium-catalyzed reactions of gamma-hydroxy internal acyclic alkenes with aryl bromides afford 2,1'-disubstituted tetrahydrofurans in good yields with diastereoselectivities of 3-5:1. The analogous transformations of substrates bearing internal cyclic alkenes afford fused bicyclic and spirocyclic tetrahydrofuran derivatives in good yields with excellent diastereoselectivities (>20:1). A series of deuterium labeling experiments indicate that the origin of the modest diastereoselectivity in reactions of acyclic internal alkene substrates likely derives from a series of reversible beta-hydride elimination and sigma-bond rotation processes that occur following a rare intramolecular alkene syn-insertion into an intermediate Pd(Ar)(OR) complex. In addition, these studies shed light on the chemoselectivity of insertion, suggesting that the alkene inserts into the Pd-O bond in preference to the Pd-C bond.
Hay
Michael B
MB
Department of Chemistry, University of Michigan, 930 North University Avenue, Ann Arbor, Michigan 48109-1055, USA.
Wolfe
John P
JP
D000475:Alkenes / Q000737:chemistry*; D002384:Catalysis; D005663:Furans / Q000138:chemical synthesis* / Q000737:chemistry*; D006859:Hydrogen / Q000737:chemistry; D015394:Molecular Structure; D010100:Oxygen / Q000737:chemistry*; D010165:Palladium / Q000737:chemistry*; D013237:Stereoisomerism
D000475:Alkenes; D005663:Furans; D010165:Palladium; D006859:Hydrogen; D010100:Oxygen