Carbonylative coupling of organozinc reagents in the presence and absence of aryl iodides: Synthesis of unsymmetrical and symmetrical ketones

The utility of the palladiun(O) catalysed reaction of the iodoalanine-derived organozinc reagent 6a with functionalised aryl iodides, under a carbon monoxide atmosphere, to give protected 4-aryl-4-oxo alpha-amino acids 8, is illustrated by a short synthesis of L-kynurenine 4. Treatment of functionalised organozinc reagents with catalytic tetrakis(triphenylphosphine)palladium(O) under an atmosphere of carbon monoxide, in the absence of any electrophile leads to the formation of symmetrical functionalised ketones 9 in good yields, This reaction is illustrated by a one-step synthesis of protected (2S,6S)-4-oxo-2,6-diaminopimelic acid 9a from commercially available compounds, It has been established that adventitious molecular oxygen plays a key role in the formation of the symmetrical ketones 9, and that rigorous exclusion of oxygen can result in substantially higher yields of ketones 8 in the cross-coupling with some aromatic iodides.