ADDITION OF NON-STABILIZED CARBON-BASED NUCLEOPHILIC REAGENTS TO CHIRAL N-SULFINYL IMINES

摘要

Chiral branched amines are an extremely important class of molecules that can be found in numerous natural products and marketed pharmaceuticals.Among several general strategies for the asymmetric synthesis of amines,one of the most successful is the addition of carbon-based nucleophiles to imine derivatives bearing a readily cleavable chiral auxiliary to bias the stereoselectivity in the desired direction.1-3 Sulfinamides are one of the most widely used subsets of chiral auxiliaries.The growing number of sulfinamide-based methods and their application to total synthesis,to drug discovery,and to drug development4 is attributed to a number of practical aspects related to this chemistry.A wide range of sulfinamides can be prepared via straightforward synthetic procedures.5-18 Additionally,enantiomerically pure 4-toluene-and tert-butanesulfinamides are commercially available at a reasonable cost.N-Sulfinyl aldimines and ketimines can be synthesized using mild reaction conditions,and the resulting imines are easily handled.The iV-sulfinyl group both activates the imines for nucleophilic attack and is a powerful directing group,leading to high diastereomeric ratios and predictable asymmetric induction(Scheme 1).Cleavage of the N-sulfinyl group is achieved using mild acidic conditions.Because of the increasing popularity of sulfinamide chemistry,a number of excellent reviews have been published.19-27 This chapter provides an overview of sulfinamide chemistry through 2017,excluding the patent literature,in which a carbon-carbon bond is formed between the azomethine carbon and the nucleophile,but it does not cover reductive couplings or reactions of highly stabilized,carbon-based nucleophiles such as enolates and ylides.