Synthesis of a Constitutional Isomer of Nerol by Consecutive Ireland–Claisen and Cope Rearrangements

Abstract

(2Z,6E)-3,6-Dimethylocta-2,6-dien-1-ol (6) was synthesized by Steglich esterification of (2E)-2-methylbut-2-en-1-ol (tiglic alcohol, 7) with 3-methylbut-2-en-1-oic acid (senecioic acid, 8), followed by selective Ireland–Claisen rearrangement of the resulting ester 9 at 0°C and subsequent Cope rearrangement of the product at 140°C. A standard LAH reduction in the last step of the synthetic sequence transformed the α,β-unsaturated acid 12 into the target molecule 6, a constitutional isomer of nerol (5) with interesting olfactory properties.