SYNTHESIS OF (R)-6-METHYLTRYPTOPHAN VIA ENANTIOSELECTIVE CATALYTIC-HYDROGENATION

A novel synthesis of the potential sweetening agent (fi)-6-methyltryptophan (15) via enantioselective catalytic hydrogenation is described. The methyl (Z)-α-(acylamino)indoleacrylates 8a-c were obtained by reduction of the α-nitroindoleacrylate 6 with stannous chloride and subsequent acylation. Alternatively, decarboxylative condensation of the carboxaldehyde 12 with the ethyl half-ester of acetamidomalonic acid in acetic anhydride-pyridine furnished the ethyl ester 8d in high yield. Basic hydrolysis of 8a or 8d produced the acrylic acid 9. The asymmetric hydrogenations of these substrates with several chiral rhodium-phosphine complexes are discussed. An optimized process to convert 9 into 15 in 60% yield is presented. Catalytic hydrogenation with Rh-16b gave (R)-N-acetyl-6-methyltryptophan (14e) (82% ee) which was purified as its ammonium salt 14f (>99.8% ee) and deacetylated to afford enantiomerically pure 15. © 1979, American Chemical Society. All rights reserved.