Chiral Silyl Ketene Acetals from Thioesters: Reaction with Acetals and Peroxyacetals to form 3-Alkoxy- and 3-Peroxyalkanoates Patrick H. Dussault, * Tony K. Trullinger and Su Cho-Shultz Department of Chemistry, University of Nebraska-Lincoln, Lincoln, NE 68588-0304, USA Received 5 July 2000; accepted 26 September 2000 Abstract ÐThe Lewis acid-mediated reaction of chiral O- and S-silyl ketene acetals (SKAs) with peroxyacetals and acetals was investigated as an approach to the asymmetric synthesis of 3-peroxy- and 3-alkoxyalkanoates. SKAs derived from chiral O-acetates fail to react with peroxyacetals and provide little diastereoselection in reactions of nonperoxidic acetals. Reaction of thioacetate SKAs with peroxyacetals furnishes 3-peroxyalkanoate thioesters in good yield but with poor diastereoselection. In the case of silyl ketene acetals based upon a camphorsulfonamide chiral auxiliary the diastereomeric peroxyalkanoates are easily separated. q 2000 Elsevier Science Ltd. All rights reserved. Introduction The 3-peroxycarbonyl and homoallyl peroxide motifs are common substructures within peroxide natural products and their synthetic precursors. 1 Recent work in our group has revealed an ef®cient approach to these subunits based upon the Lewis acid-mediated reaction of peroxyacetals with electron-rich alkenes (Fig. 1). 2,3 In the course of synthetic studies towards plakinic acids, we required a method for synthesis of enantiomerically enriched 3- peroxyalkanoates. 4 We now report our investigations into the reactions of chiral silyl ketene acetal nucleophiles with prochiral peroxycarbenium ions. Given the recent advances in methodology for enantio- selective addition to prochiral aldehydes, control of stereo- chemistry in corresponding reactions of peroxyacetals might seem straightforward. However, in analogy to the corresponding reactions of nonperoxidic acetals, 5 the Lewis acid-mediated reactions of alkenes with peroxy- acetals appears to involve intermediate peroxycarbenium ion. Given this mechanistic assumption, neither the chirality of the acetal, the Lewis acid, or the leaving group is likely to exert a signi®cant in¯uence on product stereochemistry. We were therefore drawn to the use of chiral nucleophiles, of which chiral silyl ketene acetals (SKAs) appeared to be ideal candidates. Several classes of chiral SKAs undergo highly stereoselective Lewis acid-mediated aldol reactions with prochiral aldehydes; in at least one example, reaction is postulated to proceed via an open transition state. 6±8 In addition, the retention of the auxiliary chiral center in the ester product provides a handle for resolution of stereo- isomeric products. Finally, peroxyalkanoates are easily saponi®ed or reduced without destruction of the peroxide. 2,9 Results and Discussion Several substrates were employed for these studies (Fig. 2). A monoperoxyacetal (1), prepared via transacetalization of benzaldehyde dimethyl acetal, offered a model for additions to secondary peroxycarbenium ions. Alkoxydioxolane 2, prepared from 4-methyl-3-pentan-2-one according to a Tetrahedron 56 (2000) 9213±9220 Pergamon TETRAHEDRON 0040±4020/00/$ - see front matter q 2000 Elsevier Science Ltd. All rights reserved. PII: S0040-4020(00)00894-2 Figure 1. Figure 2. Keywords: thioester; chiral auxiliary; silyl ketene acetal; peroxide. * Corresponding author. Tel.: 11-402-472-2732; fax: 11-402-472-9402; e-mail: pdussault1@unl.edu