Some Routes to Chiral Sulfoxides with Very High Enantiomeric Excesses

Abstract

In the first part of this Account, the preparation of chiral sulfoxides by the asymmetric oxidation of prochiral sulfides is described, emphasizing recent results obtained when the oxidation is mediated by chiral titanium complexes. This approach is very successful for the asymmetric synthesis of compounds with the structure Ar-S(O)-Me. In the second part of the review, a new synthetic scheme for preparing chiral sulfoxides is discussed. It involves the initial stereoselective preparation of a chiral sulfite, which in two substitution reactions is converted into various families of enantiomerically pure sulfoxides with a predictable absolute configuration. This approach is especially useful for dialkyl sulfoxides or various types of tert-butyl sulfoxides. 1. Introduction 2. Asymmetric Oxidation of Sulfides 2.1. Development of the Water-Modified Chiral Titanium Reagent 2.2. Mechanism 2.3. Improvements of Enantioselectivity 2.4. Catalytic Reactions 2.5. Conclusion 3. Cyclic Sulfite Transformation to Enantiomerically Pure Sulfoxides 3.1. Strategy 3.2. Presentation of the Method 3.3. Structure of Chiral Cyclic Sulfite 4a 3.4. Stereochemistry of the Substitutions 3.5. Scope and Limitations 4. Conclusion