(4E,8Z)-12-Methyloxacyclotetradeca-4,8-dien-2-one and Its 7a-Homologue: Conformationally Constrained Double-Unsaturated Macrocyclic Musks by Ring-Closing Alkyne Metathesis

Abstract

The double-unsaturated macrocyclic lactones (4E,8Z)-12-methyloxacyclotetradeca-4,8-dien-2-one and its 7a-homologue (4E,9Z)-13-methyloxacyclopentadeca-4,9-dien-2-one, designed as new potent musk odorants by molecular modeling, were synthesized by ring-closing alkyne metathesis in the presence of 10 mol% of Schrock’s alkylidyne catalyst, and subsequent Lindlar hydrogenation. Demethylation of citronellol, induced by nitrous acid, afforded the 3-methyloct-6-yn-1-ol building block. The substrates for the alkyne metathesis were prepared by Steglich esterification of citronellol with the 3E-configured non-3-en-7-ynoic and dec-3-en-8-ynoic acids, accessible by β,γ-selective Knoevenagel condensation from the corresponding alkynals hept-5-ynal and oct-6-ynal, which were synthesized by Eschenmoser-Ohloff fragmentation of the epoxide of 2-methylcyclohex-2-enone, and methylation of hex-5-yn-1-ol, respectively. Both target structures, (4E,8Z)-12-methyl­oxacyclotetradeca-4,8-dien-2-one and its 7a-homologue, emanated most pleasant and powerful musk odors.

Key words

odorants - macrocycles - metathesis - musks - ring closure

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1

This work was carried out during a six-month research practical at the Givaudan Schweiz AG, Fragrance Research. New address: Lehrstuhl für Organische Chemie I, Technische Universität München, Lichtenbergstraße 4, 85747 Garching, Germany.