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 °C] of several benzo[b]thiophene boronic acids with the methyl esters of N-tert-butyloxycarbonyl-β-bromodehydroalanine [Boc-ΔAla(β-Br)-OMe] or N-tert-butyloxycarbonyl-β-bromodehydroaminobutyric acid [Boc-ΔAbu(β-Br)-OMe]. The β-bromodehydroamino acid 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-ΔAla(β-Br)-OMe. However, for Boc-ΔAbu(β-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. (© Wiley-VCH Verlag GmbH, 69451 Weinheim, Germany, 2002)