Efficient synthesis of 5,6,7-trisubstituted 1H-pyrrolizines

Crystalline phosphorus ylides are obtained in excellent yields from the 1:1 :1 addition reaction between triphenylphosphine, dialkyl acetylenedicarboxy lates and strong NH-acids, such as 2-pyrrolylglyoxalate or N-benzyl-2-pyrro lylglyoxamate. These phosphoranes undergo a smooth intramolecular Wittig re action in boiling toluene to produce 5,6,7-trisubstituted 1H-pyrrolizine de rivatives in quantitative yields. Dynamic NMR effects are observed in the H -1 NMR spectra of stabilized ylides 6a and 6d (DeltaG(not equal)=67.6 and 6 9.5 kJ mol(-1), respectively) and are attributed to restricted rotation aro und the carbon-carbon partial double bond resulting from conjugation of the ylide moiety with the adjacent carbonyl group. (C) 2001 Elsevier Science L td. All rights reserved.