A. Abramovitch, L. Fensterbank, M. Malacria
Aug 25, 2008
Citations
0
Influential Citations
28
Citations
Journal
Angewandte Chemie
Abstract
Cyclopropane is a basic structural element in a wide range of naturally occurring compounds, and has been used as a versatile intermediate in the synthesis of more functionalized cyclic and acyclic alkanes. In the last few decades, most of the synthetic efforts have focused on the enantioselective synthesis of cyclopropanes, however, new and more efficient methods for the preparation of these entities in enantiomerically enriched form are still evolving. These methods can be divided into four types: the halomethylmetal-mediated cyclopropanation reaction, the transition-metal-catalyzed decomposition of diazo compounds, the nucleophilic addition/ring closure sequence, and the hydroand carbometalation reaction of strained cyclopropene derivatives. All of these methods are among the most powerful and innovative approaches, but they usually lead to functionalized cyclopropanes. To prepare nonfunctionalized, enantiomerically enriched disubstituted cyclopropanes (95% ee), we successfully reported the ( )-sparteine-catalyzed enantioselective carbolithiation of styrenyl derivatives which then undergo a 1,3-elimination reaction. These reactions were restricted to aryland vinyl-substituted cyclopropanes. To develop an even more general approach to the preparation of enantiomerically pure polyalkylated cyclopropanes (1; R, R, R = alkyl groups), we envisaged subjecting 2 to a combination of two consecutive selective sulfoxide/lithium exchanges, a transmetalation reaction, and then a reaction with an electrophile (Scheme 1). The sulfoxide/lithium exchange occurs when the reactive organometallic reagent reacts at the sulfur center of the sulfoxide, through an SN2 process, to generate a more stable organometallic leaving group. Alkylidene bis(p-tolylsulfoxides) (3) were recently used as highly versatile partners for asymmetric syntheses in the context of radical chemistry, polar Michael additions, and the Michael-initiated ring closure reaction which is used herein as the key step for the preparation of cyclopropane 2. Indeed, when the sulfur ylide, generated in situ by deprotonation of trimethyloxosulfonium iodide with NaH in DMSO, was reacted with alkylidene bis(p-tolylsulfoxides) 3a–c and corresponding bis(p-tolylsulfinyl)cyclopropanes 2a–c were obtained in good to excellent diastereoisomeric ratios (Scheme 2). Each of the products 2b and 2c were easily separated by column chromatography on silica gel to obtain each diastereoisomer as a pure isomer. The absolute configuration of 2a was determined by X-ray crystallographic analysis (see the Supporting Information) and by using the already established model.