269407-38-7Relevant articles and documents
A one-pot bicycloannulation method for the synthesis of tetrahydroisoquinoline systems
Padwa, Albert,Beall, L. Scott,Heidelbaugh, Todd M.,Liu, Bing,Sheehan, Scott M.
, p. 2684 - 2695 (2007/10/03)
A highly effective method for the synthesis of the core indolo[2,3- α]quinolizidine skeleton found in yohimbine is described. The reaction of N- monosubstituted thioamides with bromoalkenoyl chlorides furnishes thioisomunchnones as transient 1,3-dipoles that undergo ready intramolecular cycloaddition across the tethered π-bond to give thio-bicycloannulated products in a one-pot operation. The stereochemical outcome of the intramolecular reaction is the consequence of an endo cycloaddition of the neighboring π-bond across the transient thioisomunchnone dipole. A major limitation of the method is that when a hydrogen is present in the α- position of the thioamide the initially formed thio-N-acyliminium ion undergoes proton loss to produce a S,N-ketene acetal at a faster rate than dipole formation. Treatment of tetrahydro-β-carboline-1-thione with 2- bromooct-7-enoyl chloride followed by reductive removal of sulfur from the cycloadduct resulted in the formation of (±)-alloyohimbanone. Attempts to cycloadd the thioisomunchnone dipole across several nucleophilic π-bonds failed, and instead, products derived from cyclization of the π-bond onto the initially formed thio-N-acyliminium ion were formed. The resulting N,S- ketals were further converted into several tetrahydroisoquinoline alkaloids in good yield.
