Efficient diastereo- and enantioselective synthesis of α,β-disubstituted γ-phosphono sulfonates

The first asymmetric synthesis of alpha,beta-disubstituted gamma-phosphono sulfonates is reported. The key step is the Michael addition of a lithiated enantiopure sulfonate bearing an inexpensive chiral sugar auxiliary to alpha,beta-unsaturated phosphonates in good diastereoselectivities. After chromatographic purification, the cleavage of the chiral sugar auxiliary proceeds without any epimerization or racemization to form the corresponding isopropyl sulfonate in very good overall yield (75%) and excellent diastereomeric and enantiomeric excess (de, ee >= 95%). (C) 2009 Elsevier Ltd. All rights reserved.