Activating tert-butyl hydroperoxide by chelated vanadates for stereoselectively preparing sidechain-functionalized tetrahydrofurans.

tert-Butyl hydroperoxide (TBHP) stereoselectively oxidizes substituted 4-pentenols, when activated by (ethyl)[cis-(piperidine-2,6-diyl)dimethyl] vanadates. The reaction affords (tetrahydrofuran-2-yl)methanols in up to 89% yield, and in stereoselectivity ranging between moderate (cis:trans=32:68) to excellent (>99:1). Correlating structures of 4-pentenols, differing by substitution at tetragonal and trigonal stereocenters, to configuration of products obtained from oxidative cyclization provides a reaction model explaining the origin of stereoselectivity by (i) intramolecular oxygen atom transfer to (ii) a chair-like folded alkenol, being (iii) hydrogen-bonded to one of the two aminodiolate oxygens of the chelated vanadate, having (iv) substituents in the chair-like transition structure preferentially aligned equatorially. Substituents at trigonal stereocenters improve 2,5-cis- and 2,4-trans-selectivity for oxidative 4-pentenol cyclization in case of (Z)-configuration. An (E)-substituent does not alter selectivity exerted by a terminal (Z)-substituent of similar steric size. Larger (E)-groups increase the fraction of 2,5-trans-cyclized products. The reaction model additionally implements results from vanadium-51 NMR spectroscopy and density functional theory. According to theory, the (dialkoxy)(oxo)vanadium substituent exerts in the preferred end-on conformation almost no effect on structure and bonding of the peroxide group in tert-butylperoxy vanadates. Changing conformation to a higher in energy side-on arrangement puts the vanadate-bound tert-butylperoxy group into a position to serve in a concerted reaction as combined electron acceptor and oxygen atom donor.