Asymmetric synthesis of β-amino-γ-substituted-γ-butyrolactones: double diastereoselective conjugate addition of homochiral lithium amides to homochiral α,β-unsaturated esters

Abstract

Chiral alpha,beta-unsaturated esters, containing a single, gamma-stereogenic centre, show modest levels of substrate control upon conjugate addition of lithium dibenzylamide. Double diastereoselective conjugate additions of homochiral lithium N-benzyl-N-(alpha-methylbenzyl)amide to the homochiral alpha,beta-unsaturated esters display "matching" and "mismatching" effects. In each case, however, these additions proceed under the dominant stereocontrol of the lithium amide to give the corresponding beta-amino esters in high de. A remarkable reversal in stereoselectivity is noted by changing the ester functionality to an oxazolidinone. Subsequent O-deprotection and cyclisation of the resultant beta-amino adducts gives access to the corresponding beta-amino-gamma-substituted-gamma-butyrolactones in good yield and high de.