OPr i Ti O N O O R R R O Ti O N O O R R R R OH N OH R HO R O Bu t 2 3 1a R = Me b R = Ph c R = H Polynuclear aggregates S SO a b c e d b %ee (S) = 40–84% 4 Use of electrospray ionization mass spectrometry to characterize chiral reactive intermediates in a titanium alkoxide mediated sulfoxidation reaction Marcella Bonchio, a Giulia Licini,* a Giorgio Modena, a Stefano Moro, a Olga Bortolini,* b Piero Traldi c and William A. Nugent d a Universit` a di Padova, Dip. di Chimica Organica, CMRO del CNR, via Marzolo 1, I-35131 Padova, Italy b Universit` a di Ferrara, Dip. di Chimica, via Borsari 46, 44100 Ferrara, Italy c CSSRCC del CNR, via Marzolo 1, 35131, Padova, Italy d The Du Pont Company, Central Research and Development, PO Box 80328, Wilmington, Delaware 19880-0328, USA The ESIMS technique, combined with 1 H NMR evidence, provides a precise inventory of the catalytic Ti IV precursors and the characterization of the reactive peroxometal com- plex involved in enantioselective sulfoxidation employing the Ti IV –homochiral trialkanolamine–alkylhydroperoxide system. In the field of titanium(IV) alkoxide mediated homogeneous enantioselective oxidation using alkyl hydroperoxides as oxy- gen donors, 1 excellent results have been obtained in the asymmetric epoxidation of allylic alcohols 2 and in the sulfoxi- dation of sulfur containing compounds. 3 Characterization of the active catalysts in many of these reactions is complicated by the tendency of the alkoxides to form mixtures of polynuclear species equilibrating in solution. 4 In all cases a chiral titanium h 2 -alkylperoxo species has been postulated as the reactive intermediate. 5 In this respect, the solid-state structure of the achiral h 2 -tert-butylperoxo titanatrane dimer, in which the peroxide moiety has an h 2 arrangement, is so far the only characterized titanium(IV) peroxo complex. 6 We recently developed a highly robust titanium alkoxide catalyst 7 for the enantioselective oxidation of organic sulfides to sulfoxides. 8 Catalyst 2 is generated in situ by addition of a stoichiometric amount of the homochiral trialkanolamine 1, to a CHCl 3 solution of Ti(OPr i ) 4 (Scheme 1, pathway a). 7,8 Described here is the novel observation that the catalytically active polynuclear titanium(IV)-based species 4 forms from the interaction of 2 and excess of ligand 1 (Scheme 1, pathway e). Our results include electrospray ionization mass spectrometric (ESIMS) studies 9 † which, together with 1 H NMR evidence, allow (i) identification of the components in 4, (ii) delineation of their reactivity with oxygen nucleophiles and (iii) character- ization of the monomeric chiral titanium(IV) peroxo species 3 arising from the interaction of 2 and 4 with Bu t OOH (Scheme 1, pathway b). 1 H NMR studies in CDCl 3 indicate that when a precise 1 : 1 ligand : titanium ratio is employed the discrete monomeric complex 2 is formed.‡ Further addition of 1 causes the progressive disappearance of the resonances of the apical isopropoxy ligand in 2 and the synchronous appearance of two broader signals indicating the formation of a mixture of aggregates.§ The room-temperature 1 H NMR spectrum of 4b shows broad resonances and the absence of isopropoxy signals.¶ At lower temperature (220 °C) the system freezes out and a complicated spectrum of sharper signals is obtained, consistent with the presence of a steady composition of aggregates. In contrast, at 60 °C only three broad singlets are observed, each corresponding to a different set of protons. However, regardless of the amount of 1 in excess, addition of Bu t OOH to the system always restores a simple 1 H NMR spectrum consistent with the mononuclear tert-butylperoxo- titanium species 3. 8 ESIMS analysis, which has already been applied successfully to the characterization of various polynuclear complexes, 9,10 allowed us to identify the diverse species present in solution. The positive ion ESI mass spectrum of preformed catalyst 4a using methanol as the mobile phase is shown in Fig. 1. The most significant ions, whose structures have been assigned on the basis of MS/MS analysis and comparison between the theoretical and experimental cluster ion peaks, are indicated. The overall ESIMS spectrum of Fig. 1 shows the molecular peaks of the species originated in the equilibrium reactions involving the titanium centre and the oxygen nucleo- philes available in solution, i.e. trialkanolamine 1a, methanol and water, present in traces in the mobile phase. Interaction of 4a with water, gives rise to ions I (m/z 254), IV (m/z 489) and VII (m/z 724) which are mono-, di- and tri-nuclear titanium containing species, respectively. Those ions show incorporation of 18 O (! 65%) when H 2 18 O is added to the mobile phase. The reaction of 4a with methanol is responsible for the appearance of ions II (m/z 268) and V (m/z 503), whose mass peaks show an increment of four and three mass units, respectively, when CD 3 OD is used as the mobile phase. Multiple interaction of 1a with Ti IV 11 affords species VIII (m/z 897) and the lower homologue ions VI (m/z 662) and III (m/z 427).∑ These latter ions were also observed in the positive-ion ESI mass spectrum collected for an acidic chloroform solution of 4a i.e. under conditions similar to those employed in catalytic sulfoxidation. 8 Complexes 4b and 4c give analogous ESI mass spectra where the same reactivity pattern can be recognized.** Additional support for the NMR results comes from the characterization of the protonated titanium(IV) peroxo complex 3a (m/z 326), achieved by ESIMS 13 when an excess of tert- butylhydroperoxide was added to the mobile phase containing 4a. The structure of the cluster ion peaks and the MS/MS analysis of the 326 mass peak (Fig. 2) are consistent with the Scheme 1 Reagents and conditions: a, stoichiometric Ti(OPr i ) 4 , CHCl 3 , 20 °C; b, Bu t OOH; c, Pr i OH; d, Ti(OPr i ) 4 (0.75 equiv.), CH 2 Cl 2 , 20 °C, followed by solvent removal; e, excess of 1 Chem. Commun., 1997 869 Published on 01 January 1997. Downloaded on 27/10/2014 13:55:22. View Article Online / Journal Homepage / Table of Contents for this issue