Substitution induced switch between Pictet-Spengler and Eschweiler-Clarke reactions: Selective synthesis of spiro acenaphthylene pyrrolo[1,2-b]-isoquinoline/pyrrolidine hybrids

Abstract

The 1,3-dipolar cycloaddition of azomethine ylides generated in situ from the decarboxylative condensation of acenaphthenequinone and tyrosine or phenylalanine to β-nitrostyrenes afforded spiro acenaphthylene-pyrrolidine hybrids. The subsequent reaction of these spiro heterocycles with formaldehyde and trifluoroacetic acid led to the formation of either Pictet-Spengler or Eschweiler-Clarke products depending on the substitution in the benzyl ring. The unsubstituted compounds occurred via Pictet-Spengler route to afford spiro acenaphthylene pyrrolo[1,2-b]isoquinoline hybrids as expected, whereas the 4-OH substituted compounds proceeded via Eschweiler-Clarke route affording the unexpected N-methylated spiro acenaphthylene-pyrrolidine hybrids.