Preparation of macrocyclic musks via olefin metathesis: comparison with classical syntheses and recent advances

Abstract

Recent advances in the synthesis of macrocycles with musk scent via catalytic olefin metathesis are presented with a particular emphasis on advantages offered by the metathesis technology. The review includes short historical background about musks and olefin metathesis to introduce the subject. Substantial emphasis is given on ring-closing metathesis (RCM) as a tool for the synthesis of cyclic compounds such as civetone, muscone, exaltolide, ambrettolide/isoambrettolide, and yuzu lactone. The bibliography includes 106 references.

Large‐Scale Synthesis of a Niche Olefin Metathesis Catalyst Bearing an Unsymmetrical N‐Heterocyclic Carbene (NHC) Ligand and its Application in a Green Pharmaceutical Context

“…Given the mild reactionc onditions and high atom-economy,t he catalytic olefin metathesis reaction [4] is currently undergoing at hriving development as a powerful transformation leadingt oc omplex organic molecules, including natural products, Active Pharmaceutical Ingredients (APIs), [5] and much more. [6] In the same context,i ti si mportant to notet hat the particular class of metathesis catalysts belonging to the family of ruthenium(II)c arbene complexes is not very sensitivet owards air and moisture, and in general is compatible with so-called "greens olvents",s uch as 2-MeTHF,ethyl and methyl carbonate, ethyl acetate, [7] and even more polar media, such as water, [8] alcohols [9] or ethyl lactate. [10] This attribute is primarily because of the existing consensus regarding the pressing need to switcha way from fuel-based aromatic or chlorinated solvents to their more ecologically friendly and green alternatives.…”

Synthesis of Cyclic Fragrances via Transformations of Alkenes, Alkynes and Enynes: Strategies and Recent Progress

“…The power of organic synthesis for fragrances was unlocked in 1868 when coumarin was successfully prepared by W. H. Perkin from salicylaldehyde. With the blossoming of organic synthetic methods and the related industrial technologies over the past century, synthetic and semi-synthetic fragrances emerged to become mainstream in the flavors and fragrances industries [ 2 , 18 , 19 , 20 , 21 , 22 , 23 , 24 , 25 , 26 , 27 , 28 , 29 , 30 , 31 , 32 , 33 , 34 , 35 , 36 ]. Nowadays, fragrance molecules represent an attractive testing ground and offer a multi-billion-dollar outlet for organic synthesis, stimulating researchers in academia and fragrance manufacture to seek out new fragrances and explore more efficient, economical, scalable and environmentally friendly synthetic methods.…”

“…With classic or new odorants as targets, innovative synthetic strategies and methods have been developed recently that enrich the frontiers of alkene and alkyne chemistry. Though there are a few reviews published on fragrance synthesis [ 2 , 18 , 19 , 20 , 21 , 22 , 23 , 24 , 25 , 26 , 27 , 28 , 29 , 30 , 31 , 32 , 33 , 34 , 35 , 36 ], the importance of unsaturated hydrocarbons in this area is still underestimated, especially that of alkynes and enynes.…”

Synthesis of mixed musks via Eschenmoser–Tanabe fragmentation, enyne metathesis and Diels–Alder reaction as key steps

“…In the flavour and fragrance industry, musks are used as perfume additives on a large scale. 2 These compounds are also used as personal care products which include insect repellent, UV filters, preservatives and antimicrobial agents. There are a wide range of personal care products (PCPs) that contain synthetic musks, including lotions, shampoos, perfumes, softeners, air fresheners, washing powders etc.…”