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 (NRRR3)-R-1-R-2, where R-1 = CH2COO 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 (H2LB); 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 (CH3){CH2CHPh(OH)}(CH2CO2-), HLE* (asterisk refers to unprotected carboxylate). Reaction of these ligands with VO(OiPr)(3) in CH2Cl2 gave the oxovanadium(V) complexes [VOL(OiPr)(2)] and [VOL2-(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-HLC, S-HLD, R,S-HLE*center dot H2O, and Lambda[VO(R,S-L-B')OMe] have been determined. The complex [VOLB'(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 [VOLA(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 V-51 NMR of the catalysts [VOL(OR)] and the oxo-peroxo intermediates [VOL(O2R')]. 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).