Efficient Synthesis of (−)‐(R)‐Muscone by Enantioselective Protonation

Abstract

A new synthesis of (À)-(R)-muscone ((R)-1) by means of enantioselective protonation of a bicyclic ketone enolate as the key step (see 6 3 (S)-4 in Scheme 2) is presented. The C 15 macrocyclic system is obtained by ozonolysis (Scheme 7).

Enantioselective Iridium‐Catalyzed Allylic Arylation

“…[a] All experiments were run on a 0.5 mmol scale of 1 in THF (2.5 mL) according to the optimal conditions ( [38] The double bond of the resulting unsaturated ester 6 was then reduced under mild conditions by using a coppercatalyzed 1,4-reduction reaction [39] leading to ester 7, a known intermediate in Davies synthetic approach to sertraline.…”

Flavours and Fragrances

“…[199,200] In 2004, Firmenich published a synthesis of enantomerically pure (R)-muscone, the key step of which is the enantioselective protonation of an enolate. [201] The starting material is obtained by methylation of bicyclo [10.3.0]pentadec-1(12)-en-13-one. [172] Isopropylephedrine proved to be the best chiral acid for the enantioselective protonation, as in case of damascone (cf.…”

New Oxa‐Bridged Macrocycles

“…Colorless oil. (11). Compound 9 (2 g, 0.007 mol) and 0.5 g TsOH were dissolved in 30 ml acetone, and the mixture was stirred at 358 for 5 h, prior to evaporation of the solvent.…”

“…Fehr et al have described the synthesis of alcohol 30 with a five-instead of sixmembered ring system [11] (Scheme 7).…”