Functionalized Tetrahydrofurans from Alkenols and Olefins/Alkynes via Aerobic Oxidation−Radical Addition Cascades

Abstract

Aerobic oxidation of alkyl- and phenyl-substituted 4-pentenols (bishomoallyl alcohols), catalyzed by cobalt(II) complexes in solutions of γ-terpinene or cyclohexa-1,4-diene, stereoselectively gave tetrahydrofurylmethyl radicals. Cyclized radicals were trapped with monosubstituted olefins (e.g., acrylonitrile, methyl acrylate), (E)- and (Z)-1,2-diacceptor-substituted olefins (e.g., dimethyl fumarate, fumarodinitrile, N-phenyl maleic imide), and ester-substituted alkynes (e.g., ethyl propynoate). Oxidation-addition cascades thus furnished side-chain-substituted (CN, CO(2)R, COR, or SO(2)R) di- and trisubstituted tetrahydrofurans in stereoselective reactions (2,3-trans, 2,4-cis, and 2,5-trans). A diastereomerically pure bistetrahydrofuran was prepared in a cascade consisting of two aerobic oxidations, one alkyne addition, and one final H-atom transfer.

Enantioselective Copper‐Catalyzed Carboetherification of Unactivated Alkenes

“…Significant effort in this field has resulted in the synthesis of diverse oxygen heterocycle products with predictable regio-and diastereoselectivity. [3][4][5][6][7][8][9][10][11][12] While the related synthesis of enantiomerically enriched nitrogen heterocycles by either palladium-or copper-catalyzed enantioselective alkene carboamination methodologies has been substantially developed in recent years, [13,14] advances in reaction technology for catalytic enantioselective carboetherification/cyclization of unactivated alkenes have largely remained elusive. [15] Notable exceptions include palladium-catalyzed reactions of ortho-vinyl phenols, reactions which proceed through quinone methide intermediates, [16] and palladium-catalyzed cyclizations of g-and dunsaturated phenols which terminate in carbonylation or olefin insertion (whose substituted intermediates are unable to undergo b-hydride elimination).…”

Recent advances in the synthesis of tetrahydrofurans and applications in total synthesis

“…125 This method allows the formation of di-and tri-substituted THF with excellent trans-2,5-selectivity, and even bistetrahydrofurans, although in poor yield. Recently, a carboetherification method was reported by the group of Chemler, leading to the formation of tricycle including a THF ring in good to excellent yield, probably through a radical intermediate.…”

Recent Advances in Cascade Reactions Initiated by Alcohol Oxidation

“…Tetrahydrofurans can be stereoselectively (2,3‐ trans , 2,4‐ cis , and 2,5‐ trans ) prepared by aerobic oxidation–addition cascades from alkyl‐ and phenyl‐substituted 4‐pentenols (bishomoallyl alcohols) with cobalt(II) diketonate complexes as catalysts (Scheme and also Scheme for a stereoselective example) . A sequence of polar and free‐radical reactions occurs in this case, which thus allows one‐pot chemical transformations not available from oxidation catalysis or radical chemistry alone.…”