Science of Synthesis

Kubik, S., Science of Synthesis Knowledge Updates, (2013) 3, 268.

Cyclization of α-amino amides under carbonylation conditions leads directly to hydantoins. This reaction is closely related to a number of urea syntheses described in Section ‌18.8.22.1‌. The transformation can therefore be achieved with similar reagents such as 1,1′-carbonyldiimidazole,[‌217‌] bis(4-nitrophenyl) carbonate,[‌218‌] or 4-nitrophenyl chloroformate.[‌219‌] Enantiomerically pure amides of α-amino acids can be converted into the corresponding hydantoins ‌48‌ with almost complete preservation of stereochemical integrity (>96% ee) by using bis(trichloromethyl) carbonate as the carbonylating agent in the presence of pyridine (‌Scheme 80‌).[‌220‌] Carbonylation of α-amino amides can also be achieved by employing oxidative catalytic carbonylation using hexacarbonyltungsten(0) as the catalyst, iodine as the oxidant, carbon monoxide as the carbonyl source, and 1,8-diazabicyclo[5.4.0]undec-7-ene as the base (see Section ‌18.8.22.1.1.12.1‌).[‌221‌] Secondary amides can be used in this reaction although the yield drops considerably as the steric bulk of the substituent on the nitrogen atom increases.

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References