Asymmetric Synthesis of (S)-4-Oxopipecolic Acid by a 3+3 Atom-Unit Assembly Strategy

(S)‐4‐Oxopipecolic acid has been prepared in enantiomerically pure form from two readily accessible starting materials, (R)‐N‐(cyanomethyl)‐4‐phenyloxazolidine (2) and 2‐(methoxymethoxy)allyl chloride, (3, MOM‐allyl chloride). This strategy exploits the complementary electrophile/nucleophile reactivity at each end of this pair of 3‐atom unit building blocks. Thus, alkylation of the anion of 2 with 3 (creation of the piperidine C‐2−C‐3 bond) followed by Lewis acid induced cyclisation (creation of the C‐5−C‐6 bond), leads principally to a bicyclic intermediate 5 which incorporates a protected form of the title compound. Subsequent chemical transformations lead to the target molecule in an overall yield of 20% for the five‐step sequence. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2003)