Synthesis of Macrocyclic Lactones by Use of π-Allylic Nickel Complexes and Its Application to the Synthesis of Natural Products

Abstract

Based on the facile reactivity of π-allylic nickel complexes toward alkyl halides in aprotic polar solvents, synthesis of macrocyclic lactones via intramolecular alkylation of π-allylic nickel complexes was investigated. (Z)-5-Bromo-3-pentenyl ω-chloroalkanoates [12]pr e pared from (Z)-5-[(tetrahydro-2 H-pyran-2-yl)oxy]-3-penten-1-ol in several steps, were allowed to react with nickel carbonyl in benzene to form the corresponding π-allylic nickel complexes [13], which were then treated with sodium iodide in N-methyl-2-pyrrolidon e affording unsaturated lactones [14] in trans-form in good to fair yields as shown in Table 1. Some of the lactones thus prepared were converted to natural fragrance compounds, e.g.exaltolide [16] and (Z)-9-dodecen-12-olide [7], by hydrogenation and isomerization, respeCtively.
The present method of lactone formation was further applied to the facile synthesis of (±)-recifeiolide [8] as shown in Scheme 4. Thus, (Z)-6-bromo-4-hexen-2-yl 6-halohexanoate (21), prepared from propargyl tetrahydropyranyl ether in five steps, was cyclized via the π-allylic nickel complex to give [8] in 32% yield.