Glycine- and sarcosine-based models of vanadate-dependent haloperoxidases in sulfoxygenation reactions

Reaction of R-styreneoxide with glycine-tert-butylester yielded amino alcohols of the general formula NR(1)R(2)R(3), where R(1) = CH(2)COO t Bu and R(2) = R(3) = 2-phenyl-2-hydroxyethyl (H(2)LA); R(2) = 2-phenyl-2-hydroxyethyl and R(3) = 1-phenyl-2-hydroxyethyl (H(2)L(B)); R(2) = H and R(3) = 2-phenyl-2-hydroxyethyl (HLC); and R(2) = H and R(3) = 1-phenyl-2-hydroxyethyl (HLD). The corresponding reaction with sarcosine-tert-butylester and subsequent hydrolysis provided the zwitterion (+)NH(CH(3)){CH(2)CHPh(OH)}(CH(2)CO(2)(-)), HL(E)(*) (asterisk refers to unprotected carboxylate). Reaction of these ligands with VO(OiPr)(3) in CH(2)Cl(2) gave the oxovanadium(V) complexes [VOL(OiPr)(2)] and [VOL(2)-(OiPr)] (for L(C) and L(D)) or, when reacted in the presence of MeOH, [VOL'(OMe)], where L' represents the methyl ester of L(A), L(B), and L(E). The crystal and molecular structures of R-HL(C), S-HL(D), R,S-HL(E)(*)center dot H(2)O, and Lambda[VO(R,S-L(B)')OMe] have been determined. The complex [VOL(B)'(OMe)] contains vanadium in a distorted trigonal-bipyramidal array (tau = 0.72), the oxo group in the equatorial plane, and methoxide and N in the apical positions, and thus, it structurally models the active center of vanadate-dependent haloperoxidases. The structure and the bonding parameters, including a particularly long d(V-N) of 2.562 angstrom, are backed up by DFT calculations. The isolated oxovanadium(V) complexes and the in situ systems L + VO(OiPr)(3) catalyze the oxidation, by cumylhydroperoxide HO2R', of prochiral sulfides (MeSPh, MeSp-Tol, PhSBn) to chiral sulfoxides plus some sulfone. The best results with respect to enantioselectivity (enantiomeric excess (ee) = 38%) were obtained with the system VO(OiPr)(3)/L(A), and the best selectivity with respect to sulfoxide (100%) was obtained with [VOL(A)(OiPr)]. The reaction with the hexacoordinated [VO(OMe)(HOMe)L(D)*] was very slow. Oxidation of PhSBn is faster than that of MeSPh and MeSpTol. Turn-over numbers are up to 60 mol of sulfoxide mol(-1) of catalyst h(-1) (-20 degrees C). The unspectacular ee apparently is a consequence of flexibility of the active catalyst in solution, as shown by the (51)V NMR of the catalysts [VOL(OR)] and the oxo-peroxo intermediates [VOL(O(2)R')]. As shown by DFT calculations, the peroxo ligand coordinates in the tilted end-on fashion in the axial or equatorial position (energy difference = 17.6 kJ/mol).