SYNTHESIS OF 5-ALKYL-TRYPTOPHAN AND 5-ARYL-L-TRYPTOPHAN ANALOGS VIA PALLADIUM-CATALYZED CROSS-COUPLING OF AN IODINATED CYCLIC TRYPTOPHAN TAUTOMER

Cyclic tryptophan tautomers have been shown to be useful intermediates in the preparation of optically pure tryptophans substituted in the b enzenoid ring. We have utilized cyclic tautomer 2a for the preparation of L-tryptophan derivatives bearing 5-alkyl and 5-aryl functionalitie s. Treatment of 2a with 4 equivalents of iodine monochloride provided the 5-iodo species 3a in 81% yield. Cross-coupling of 3a with arylboro nic acids or B-alkyl-9-borabicyclo[3.3.1]nonane derivatives, catalyzed by 3 mol% is(1,1'-di-phenylphosphino)ferrocene]palladium(II) chloride , afforded the 5-aryl and 5-alkyl cyclic tryptophan tautomers 3b-g in 59-79% yields. The cyclic tautomers were easily decyclized and deprote cted to give the corresponding 5-aryl- and 5-alkyl-L-tryptophans.