ChemInform Abstract: An Efficient Synthesis of 4(5)‐Benzyl‐l‐histidines Employing Catalytic Transfer Hydrogenolysis at Elevated Temperatures.

Abstract

An efficient two-step synthesis of 4(5)-benzyl- l -histidine from l -histidine was developed. A Pictet–Spengler reaction between l -histidine and benzaldehyde in the presence of excess strong base yielded 4- l -phenylspinacine within one hour. Catalytic transfer hydrogenolysis in methanol at reflux using ammonium formate rapidly converted 4- l -phenylspinacine to 4(5)-benzyl- l -histidine within five minutes. No racemization of the final product 4(5)-benzyl- l -histidine was observed using the Marfey reagent. To show the utility of this method, a series of fluorinated benzylhistidines were prepared.