New Musk Odorants: (3E)‐4‐(2′‐Alkyl‐5′,5′‐dimethylcyclopent‐1′‐enyl)but‐3‐en‐2‐ones and (3E)‐1‐Acetyl‐3‐alkylidene‐4,4‐dimethylcyclohexenes

Abstract

AbstractFour new representatives, 18, 23, 29, and 32, of the young family of dienone musks were synthesized by two general routes. The first five‐step synthetic route leading to (3E)‐4‐(2′‐alkyl‐5′,5′‐dimethylcyclopent‐1′‐enyl)but‐3‐en‐2‐onescommenced with the enolate alkylation of 2,2‐dimethylcyclopentanone (13), either directly with an alkyl halide or through the Reetz tert‐alkylation. Subsequent cerium(III)‐mediated butynol Grignard reaction, dehydration with sulfuric acid, (E)‐selective partial reduction of the triple bond with lithium aluminum hydride, and concluding pyridinium chlorochromate oxidation complemented this route. The second four‐step route leading to (3E)‐1‐acetyl‐3‐alkylidene‐4,4‐dimethylcycloalk‐1‐enes commenced with the Woods–Grignard modification on the vinylogous ester 3‐ethoxycyclohex‐2‐enone (24) employing ethylmagnesium bromide. The product 25 was then gem‐6,6‐dimethylated by its lithium enolate to provide 26, which was subjected to a Schlosser–Wittig reaction to introduce the 3‐alkylidene substituent. Dirhodium(II) caprolactamate‐catalyzed allylic oxidation with tert‐butyl hydroperoxide completed the second general synthetic scheme. The four target compounds, 18, 23, 29, and 32, were designed as diseco derivatives of a carotol lead, and they all constitute musk odorants with floral‐fruity side notes. A tert‐butyl group at the C‐6 position of the (E)‐hexa‐3,5‐dien‐2‐one skeleton was found to intensify the musk odor, and (E)‐4‐(2′‐tert‐butyl‐5′,5′‐dimethylcyclopent‐1′‐enyl)but‐3‐en‐2‐one (23) was found the most intense and interesting odorant of the series, with a very uncommon undertone of beetroot and dried fruits.(© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2008)