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(Schiff-base)vanadium(v) complex-catalyzed oxidations of substituted bis(homoallylic) alcohols - Stereoselective synthesis of functionalized tetrahydrofurans

Vanadium(v) complexes 4 have been prepared from tridentate Schiff-base ligands 3 and VO(OEt)3. All vanadium(v) compounds were characterized (IR, UV/Vis, and 51V NMR spectroscopy, and in selected examples by X-ray diffraction analysis) and were applied as oxidation catalysts for the stereoselective synthesis of functionalized tetrahydrofurans 2 starting from substituted bis(homoallylic) alcohols 1 (mono- or trisubstituted C-C double bonds). Oxidation of secondary or tertiary 1-alkyl-, 1-vinyl-, or 1-phenyl-substituted 5,5-dimethyl-4-penten-1-ols under optimized conditions [TBHP as primary oxidant and 1,2-(amino)indanol-derived vanadium(v) reagent 4g as catalyst] provided 2,5-cis-configured tetrahydrofurans in synthetically useful yields and diastereoselectivities (22-96% de). On the other hand, trans-disubstituted oxolanes (62%-96 de) were obtained from oxidations of 2- or 3-alkyl- and 2- or 3-phenyl-substituted 5,5-dimethyl-4-penten-1-ols bis(homoallylic) allyhc) alcohols. Treatment of 4-penten-1-ols (i.e. substrates with monosubstituted olefinic π-bonds) with TBHP and catalytic amounts of vanadium(v) complex 4g furnished trans-disubstituted tetrahydrofurans as major products (20-96% de), no matter whether an alkyl or a phenyl substituent was located in position 1, 2, or 3 of the alkenol chain. The mechanism of this reaction has been investigated in detail. Based on results from 51V NMR spectroscopy and competition kinetics, it proceeds by a transition metal-peroxy pathway. In an initial step, TBHP coordinates to, for example, N-(2-oxidophenyl)salicylideniminato-derived vanadium complex 4a. Subsequent alkenol binding gives rise to a "loaded" vanadium(v) peroxy complex (e.g. 60) which facilitates diastereoselective oxygen transfer, presumably onto a coordinated substrate. This step leads to the formation of functionalized tetrahydrofurans as major products. TBHP binding to the remaining vanadium(v) complex then allows a regeneration of the active oxidant, for example peroxy complex 57. The origin of the observed diastereoselectivity in this oxidation has been studied in an independent stereochemical analysis. Thus, diastereomerically enriched epoxy alcohol (1R,4R)-10 was prepared. Its treatment with 1,2-(amino)indanol-derived vanadium complex 4g affords a 91:9 mixture of cis-2-(1-hydroxy-1-methylethyl)-5-(phenyl)tetrahydrofuran (cis-6) and cis-2,2-dimethyl-6-(phenyl)tetrahydropyran-3-ol (cis-7). Similarly, a 39:61 mixture of heterocycles trans-6 and trans-7 was obtained from epoxy alcohol (1S,4R)-10, if treated with Lewis acid 4g. ( Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2003).