The synthesis of chiral b-ketosulfoxides by enantioselective oxidation and their stereocontrolled reduction to b-hydroxysulfoxides Cosimo Cardellicchio, a, * Omar Hassan Omar, a Francesco Naso, a Maria Annunziata M. Capozzi, b Francesco Capitelli c and Valerio Bertolasi d a Consiglio Nazionale delle Ricerche, Istituto di Chimica dei Composti Organometallici (ICCOM), Dipartimento di Chimica, Universita ` di Bari, via Orabona 4, 70126 Bari, Italy b Dipartimento di Scienze Agro-ambientali, Chimica e Difesa Vegetale (DISACD), Universita ` degli Studi di Foggia, via Napoli 25, 71100 Foggia, Italy c Consiglio Nazionale delle Ricerche, Istituto di Cristallografia (IC), via Amendola 122/o, 70126 Bari, Italy d Dipartimento di Chimica and Centro di Strutturistica Diffrattometrica, Universita ` degli Studi di Ferrara, via Borsari 46, 44100 Ferrara, Italy Received 8 November 2005; accepted 1 December 2005 Abstract—Various chiral non-racemic b-ketosulfoxides, a class of compounds frequently used in asymmetric synthesis, were pre- pared in good yields by tert-butyl hydroperoxide oxidation of the corresponding sulfides in the presence of a complex between tita- nium and (S,S)-hydrobenzoin. The ee values of almost all of the purified products were >98%. As ascertained by X-ray analysis and/ or by NMR spectroscopy, the use of the (S,S)-form of the ligand led to aryl b-ketosulfoxides with (R S )-configuration and to methyl phenacyl sulfoxide with the (S S )-configuration. Some of the aryl ketosulfoxides were subjected to reduction with DIBAL-H/ZnCl 2 and the corresponding b-sulfinylalcohols with an (R,R S )-configuration produced. Ó 2005 Elsevier Ltd. All rights reserved. 1. Introduction Enantiopure b-ketosulfoxides are of special interest in enantioselective synthetic strategies, since they are pre- cursors of b-sulfinylalcohols. In turn, these compounds are useful building blocks in the synthesis of natural and biologically active compounds presenting a variety of structures. 1–3 An additional recent use of the same sul- finylalcohols is represented by the enantioselective pro- tonation of lithium enolates of 2-arylcyclohexanones. 4 The stereoselective reduction of b-ketosulfoxides repre- sents the most convenient route to b-hydroxysulfoxides, while the alternative procedure, consisting of oxidation of the corresponding b-hydroxysulfides, is less fre- quently used. 5,6 In spite of their synthetic potential, the types of b-ketosulfoxides readily available are rather limited, since they are commonly prepared by the acyla- tion 1,7,8 of (S)- or (R)-methyl p-tolyl sulfoxide which, in turn, is obtained by the Andersen procedure. 2,9 In principle, in order to enlarge the number of possible structures available, chiral non-racemic b-ketosulfoxides could be produced by an enantioselective oxidation of the corresponding sulfides. 10 Various efforts have been made toward this end. 11–14 1-(Phenylsulfinyl)-propan- 2-one has been obtained by tert-butyl hydroperoxide (TBHP) oxidation in the presence of a complex between titanium and (+)-diethyl tartrate at 20 °C (60% ee). 11 The same compound has also been produced in up to 84% ee by dichlorocamphorsulfonyloxaziridine oxida- tion. 12 Phenyl phenacyl sulfoxide has been synthesized in 57% ee by an oxidation with hydrogen peroxide in the presence of chiral vanadium complexes. 13 Some b-ketosulfoxides have been obtained by oxidation with cumene-, tert-butyl- or furyl hydroperoxide, in the pres- ence of a titanium/diethyl tartrate complex at 25 °C. The sulfoxides were formed with ee values between 51% and 97%, but the isolated yields were in the range 0957-4166/$ - see front matter Ó 2005 Elsevier Ltd. All rights reserved. doi:10.1016/j.tetasy.2005.12.004 * Corresponding author. Tel.: +39 0805442077; fax: +39 0805442924; e-mail: cardellicchio@ba.iccom.cnr.it Tetrahedron: Asymmetry 17 (2006) 223–229 Tetrahedron: Asymmetry