Asymmetric total synthesis of naturally occurring (R)-(–)-enantiomer of tylophorine via intramolecular double Michael reaction

Abstract

The first asymmetric total synthesis of the naturally occurring (R)-(–)-enantiomer (1) of tylophorine was achieved with high enantioselectivity via the intramolecular double Michael reaction of α,β-unsaturated esters (10) and (20), having two different chiral auxiliaries, with t-butyldimethylsilyl trifluoromethanesulphonate in the presence of triethylamine. (–)-Phenylmenthol and (2R,4S,5R)-(–)-4-(t-butyldimethylsiloxymethyl)-5-hydroxy-2-phenyl-1,3-dioxane, readily available from D-glucose, were used as chiral auxiliaries.