title: An aerobic oxidation/homolytic substitution-cascade for stereoselective methylsulfanyl-cyclization of 4-pentenols.
abstract: 4-Pentenols (dihomoallylic alcohols) are oxidized by cobalt(II)-activated dioxygen in solutions of dimethyl disulfide and cyclohexa-1,4-diene to afford methylsulfanyl (CH3S)-functionalized tetrahydrofurans in up to 74% yield. The reaction is a cascade, composed of oxidative alkenol cyclization providing tetrahydrofuryl-2-methyl radicals, which are trapped in dimethyl disulfide. Homolytic methylsulfanyl substitution by carbon radicals is a slow reaction, as exemplified by the rate constant of k(SCH(3)) = 3 × 10(4) M(-1) s(-1) (70 °C) derived from competition kinetics for the reaction between dimethyl disulfide and the trans-2-phenyltetrahydrofuryl-5-methyl radical. Methylsulfanyl-cyclizations therefore are experimentally performed in neat dimethyl disulfide, containing the minimum amount of cyclohexa-1,4-diene necessary for attaining almost quantitative alkenol conversion. The oxidative tetrahydrofuran synthesis occurs with noteworthy (>99%) 2,5-trans-stereoselectivity, as shown by the synthesis of diastereomerically pure 2,3- and 2,3,3-substituted 5-(methylsulfanyl)methyltetrahydrofurans from stereodefined 1,2-di- and 1,2,2-trisubstituted 4-pentenols. Changing the chemical nature of the disulfide reagent or the alkenol extends the scope of alkylsulfanyl-cyclization to ethylsulfanyl-cyclization, allylsulfanyl-transfer, or tetrahydropyran synthesis.
authors: Fachbereich Chemie, Organische Chemie, Technische Universität Kaiserslautern, Erwin-Schrödinger-Straße, D-67663 Kaiserslautern, Germany.
authors: Patrick
authors: P
authors: Fries
authors: Melanie Kim
authors: MK
authors: Müller
authors: Jens
authors: J
authors: Hartung
mesh_terms: D003035:Cobalt / Q000737:chemistry; D003500:Cyclization; D004220:Disulfides / Q000737:chemistry*; D005663:Furans / Q000138:chemical synthesis* / Q000737:chemistry; D008745:Methylation; D010084:Oxidation-Reduction; D010100:Oxygen / Q000737:chemistry*; D020005:Propanols / Q000737:chemistry*; D013237:Stereoisomerism
chemical_list: D004220:Disulfides; D005663:Furans; D020005:Propanols; D003035:Cobalt; C021181:dimethyl disulfide; C006463:allyl alcohol; D010100:Oxygen