SYNTHESIS OF PROTECTED 4-OXOPIPECOLIC ACID AND 4-OXOLYSINE USING A PALLADIUM-CATALYZED COUPLING PROCESS

Reaction of the L-serine derived zinc reagent 3 with acryloyl chloride gave the 4-oxo amino acid 4, with no evidence of products arising from conjugate addition. Treatment of the adduct 4 with benzylamine gave protected 4-oxolysine 5 directly. Reduction of the ketone proceeded without significant stereoselectivity to give the 4-hydroxylysine derivatives 6 as a diastereoisomeric mixture. Treatment of the adduct 4 with HCl/ether gave 4-oxopipecolic acid benzyl ester hydrochloride 7 in quantitative yield. Evidence for initial formation of the HCl adduct 8 was obtained.