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

• Alkyl vanadates form peresters by binding one equivalent of tert-butyl hydroperoxide.
• Changing perester binding from end-on to side-on is endothermic.
• Side-on bound peresters are activated for oxidizing hydrogen-bonded alkenols.
• 4-Pentenol oxidation is strongly exothermic providing tetrahydrofuranmethanols.
• Stereoinformation from the alkenol translates into configuration of substituents at tetrahydrofuran.

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.

According to theory, the (dialkoxy)(oxo)vanadium substituent exerts almost no ground state effect on structure and bonding of the peroxide group in end-on tert-butylperoxy vanadates. Changing configuration to side-on activates the tert-butylperoxy vanadate, for stereoselectively oxidizing (+)-laurediol and other substituted 4-pentenols into derivatives of tetrahydrofuranyl-2-methanol.Figure optionsDownload as PowerPoint slide