Enantioselective Routes to Sulfoxides Based Upon the Use of Carbanionic Leaving Groups

Abstract

Several carbanionic leaving groups can be easily displaced from the sulfinyl group by organometallic reagents. The reaction follows a highly stereoselective course of inversion of configuration. Provided that a ready route to the precursor sulfinyl compound is available (e.g. an enantioselective oxidation of the corresponding sulfide), the process can be transformed into an easy and versatile procedure for the stereoselective synthesis of sulfoxides. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2003)

A Study of Factors Affecting Enantioselectivity in the Oxidation of Aryl Benzyl Sulfides in the Presence of Chiral Titanium Catalysts

“…This represents an important result because, as shown in our previous work, [9] these compounds can be easily transformed into a variety of other sulfoxides in a highly enantioselective manner.…”

“…[6] Among the various strategies that have been employed to produce optically active sulfoxides, [1][2][3] special interest has focused on the enantioselective oxidation of sulfides, [7,8] in a procedure that is also preferentially employed in the industrial synthesis of bioactive target molecules. [7,8] Furthermore, in our previous work [9] we have shown that the enantioselective oxidation is a valuable strategy for preparing sulfoxides bearing carbanionic leaving groups; this approach opens a route to many other sulfoxides that are [ not easily produced by other methods, through a straightforward displacement reaction with Grignard reagents. [9] The most successful asymmetric oxidation reactions involving sulfides [7,8] are based upon an achiral oxidant (hydroperoxides or hydrogen peroxide) in the presence of a chiral metal catalyst.…”

“…[7,8] Furthermore, in our previous work [9] we have shown that the enantioselective oxidation is a valuable strategy for preparing sulfoxides bearing carbanionic leaving groups; this approach opens a route to many other sulfoxides that are [ not easily produced by other methods, through a straightforward displacement reaction with Grignard reagents. [9] The most successful asymmetric oxidation reactions involving sulfides [7,8] are based upon an achiral oxidant (hydroperoxides or hydrogen peroxide) in the presence of a chiral metal catalyst. Among the various metal catalysts, [7,8] titanium complexes play a special role.…”

Synthesis of enantioenriched sulfoxides

“…This is primarily due to the limited number of sulfoxides, mainly dialkyl sulfoxides, that can be prepared using these precursors. 270 The development of new carbanionic leaving groups may extend the scope of this methodology.…”

Investigation of the chemoselective and enantioselective oxidation of α-thio-β-chloroacrylamides

“…10 Despite the high yields of enantiopure sulfoxides obtained using this method, its scope is limited due to the difficult preparation and limited availability of suitable chiral precursors. The development of chiral precursors that possess two leaving groups 11,12 and the use of carbanionic leaving groups 13 has extended the scope of this methodology.…”