The Chemistry of C2-Symmetric Bis(sulfoxides): A New Approach in Asymmetric Synthesis

Abstract

Keywords: Asymmetric synthesis / Chiral acyl anions / Ligand design / Bis(sulfoxides)The preparation of various racemic or enantiopure C 2 -symmetric bis(sulfoxides) has been developed over the last decades. Numerous applications in organic synthesis (anionic condensation, cycloadditions) as well as in coordination chemistry have been worked out.[a] Université P. et M. Curie, UMR 7611, MICROREVIEWS: This feature introduces the readers to the authors' research through a concise overview of the selected topic. Reference to important work from others in the field is included.

The Chemistry of C2‐Symmetric Bis(sulfoxides): A New Approach in Asymmetric Synthesis

“…In acyclic series with (S,S)-8, Solladié et al [82] and we [9] have found good yields and diastereoselectivities with aro- [83] we have proposed the model displayed in Scheme 20. The most favourable approach involves chelated transition state 74 in which nonbonding interactions between the p-tolyl group of the anion of 8, and the R group of the aldehyde Scheme 19 are minimised (compared to 75).…”

“…This was first accomplished by Aggarwal et al using a water-soluble DCC variant reagent (morpho CDI 82) to transform the formaldehyde-alkylated bis(sulfoxide) 81 into methylenebis(sulfoxide) 83 (Scheme 22). [9] Another report by Carretero et al [87] mentions the synthesis of the (S,S)-1,1-bis(ethoxycarbonyl)-2,2-bis(p-tolylsulfinyl)ethene (86), in a two-step sequence involving first a quantitative condensation with oxomalonate, followed by a dehydration of 85 with DEAD. [9] Another report by Carretero et al [87] mentions the synthesis of the (S,S)-1,1-bis(ethoxycarbonyl)-2,2-bis(p-tolylsulfinyl)ethene (86), in a two-step sequence involving first a quantitative condensation with oxomalonate, followed by a dehydration of 85 with DEAD.…”

“…We have shown over the last decade that the latter are versatile partners, generally resulting in high diastereoselectivities, for palladium-catalysed [3ϩ2] cycloadditions, [4] radical Michael-type cyclizations, [5,6] radical anti-Michael cyclizations. [9] This work is presented below (section II.5) and we are currently in the process of involving these promising compounds in a series of new applications. This led us naturally to the use of various alkylidene bis(sulfoxides), for which we have recently proposed a new synthesis.…”

Convergent Preparation of Enantiomerically Pure Polyalkylated Cyclopropane Derivatives

“…[5a] All of these methods are among the most powerful and innovative approaches, but they usually lead to functionalized cyclopropanes. [12f] Alkylidene bis(p-tolylsulfoxides) [12] (3) were recently used as highly versatile partners for asymmetric syntheses [13] in the context of radical chemistry, [14] polar Michael additions, [15] and the Michael-initiated ring closure reaction which is used herein as the key step for the preparation of cyclopropane 2. [10] These reactions were restricted to aryl-and vinyl-substituted [10] cyclopropanes.…”

“…To develop an even more general approach to the preparation of enantiomerically pure polyalkylated cyclopropanes (1; R, R 1 , R 2 = alkyl groups), we envisaged subjecting 2 to a combination of two consecutive selective sulfoxide/lithium exchanges, [12] a transmetalation reaction, and then a reaction with an electrophile (Scheme 1). [12f] Alkylidene bis(p-tolylsulfoxides) [12] (3) were recently used as highly versatile partners for asymmetric syntheses [13] in the context of radical chemistry, [14] polar Michael additions, [15] and the Michael-initiated ring closure reaction which is used herein as the key step for the preparation of cyclopropane 2. [12f] Alkylidene bis(p-tolylsulfoxides) [12] (3) were recently used as highly versatile partners for asymmetric syntheses [13] in the context of radical chemistry, [14] polar Michael additions, [15] and the Michael-initiated ring closure reaction which is used herein as the key step for the preparation of cyclopropane 2.…”