Synthesis of amino acid diazoketones

A study of carboxylic acid → diazoketone conversion was pursued employing the γ-carboxyl group of otherwise protected L-glutamic acids. The Arndt-Eistert route employing carboxylic acid chloride intermediates was found best (52% yield, 5b), performed at very low temperatures employing oxalyl chloride in dimethylformamide-tetrahydrofuran followed by diazomethane at -23°C. Alternatively, substitution of a mixed carbonic anhydride for the acyl chloride led to very similar yields (57% of 5b) of diazoketones (5). Among a series of active ester intermediates (7) examined, only the ODnp (7d) and SPfp (7f) esters were found to react (23-26% yield), at least partially, with diazomethane. The latter two reactions appear to represent the first such examples employing active esters.