Synthesis using Suzuki cross couplings of sulfur analogues of dehydrotryptophan with a definite stereochemistry

Abstract

Sulfur analogues of dehydrotryptophan (5-7) were prepared in moderate to good yields (40-80%) by Suzuki cross coupling [Pd(PPh3)(4), Na2CO3 or NaHCO3, DME/H2O, 90 degreesC] of several benzo[b]thiophene boronic acids with the methyl esters of N-tert-butyloxycarbonyl-beta-bromodehydroalanine [Boc-DeltaAla(beta-Br)-OMe] or N-tert-butyloxycarbonyl-beta-bromodehydroaminobutyric acid [Boc-DeltaAbu(beta-Br)-OMe]. The beta-bromodehydroaminoacid precursors 2 were, in turn, synthesized in high yields from the corresponding N,N-diacyldehydroamino acids 1 by treatment with trifluoroacetic acid (TFA) and N-bromosuccinimide (NBS) in two steps or in a one-pot procedure. Both procedures were stereoselective for the E-isomer of Boc-DeltaAla(beta-Br)-OMe. However, for Boc-DeltaAbu(beta-Br)-OMe, different ratios of E/Z isomers were obtained in each procedure. The stereoselectivity for the Z-isomer was increased greatly with the one-pot procedure. Pure isomers were used in the coupling reactions and the stereochemistry of the starting material was generally maintained.