When Gold Meets Perfumes: Synthesis of Olfactive Compounds via Gold-Catalyzed Cycloisomerization Reactions

Abstract

An efficient, and mild synthetic route for the preparation of functionalized volatile oxa-bicyclo[4.1.0]-hept-4-ene (29 compounds, 44–98% isolated yields) has been developed relying on the association of IPrAuCl with NaBArF. The remarkable selectivity was demonstrated on a 1 g and 25 g scale with low catalyst loadings. The synthetic utility of these low-molecular-weight enols was further demonstrated by the derivatization of some adducts and by the unprecedented olfactory evaluation of all bicyclic derivatives.

Oxygen-Tethered 1,6-Enynes and [4.1.0]-Bicyclic Ether Skeletons as Hedonic Materials for the Fragrance Industry

“…= 12.8,9.4,7.5 Hz,1H,8'),4H,8'',11,12), 1.14 (s, 3H, 10), 1.03 (s, 3H, 9), 0.90 (t, J = 7.2 Hz, 4H, 13), 0.75 -0.69 (m, 1H, 3). 13 ,4),142.45 (C,12),129.06 (2xCH,14,16),127.99 (2xCH,13,17),105.93 (CH,5),67.96 (CH2,2),35.58 (CH2,9),29.93 (C,6), 27.62 (C, 1), 22.07 (CH2, 7), 20.00 (CH2, 10), 16.62 (CH3, 8), 13.60 (CH3,11 5H,12,13,14,15,16),6.14 (d,J = 5.7 Hz,1H,4a),6.10 (d,J = 5.7 Hz,1H,4b),5.10 (d,J = 5.7 Hz,1H,5a),5.06 (d,J = 5.7 Hz,1H,5b),3.95 (d,J = 10.5 Hz,1H,2b'),3.81 (dd,J = 10.5,…”

“…The crude product was purified over silica gel flash chromatography (petroleum benzine/Et2O, 90/10) to afford S-(3-phenylprop-2-yn-1-yl) ethanethioate 18d (1.50g, 78%) as an orange oil. 2H,11,15),3H,12,13,14),1H,5),3.43 (s,2H,2),3.36 (d,J = 7.8 Hz,2H,6), 1.77 (s, 3H, 8), 1.74 (s, 3H, 9). = 12.8,9.4,7.5 Hz,1H,8'),4H,8'',11,12), 1.14 (s, 3H, 10), 1.03 (s, 3H, 9), 0.90 (t, J = 7.2 Hz, 4H, 13), 0.75 -0.69 (m, 1H, 3).…”

“…2H,11,15),3H,12,13,14),1H,5),3.43 (s,2H,2),3.36 (d,J = 7.8 Hz,2H,6), 1.77 (s, 3H, 8), 1.74 (s, 3H, 9). = 12.8,9.4,7.5 Hz,1H,8'),4H,8'',11,12), 1.14 (s, 3H, 10), 1.03 (s, 3H, 9), 0.90 (t, J = 7.2 Hz, 4H, 13), 0.75 -0.69 (m, 1H, 3). 13 ,4),142.45 (C,12),129.06 (2xCH,14,16),127.99 (2xCH,13,17),105.93 (CH,5),67.96 (CH2,2),35.58 (CH2,9),29.93 (C,6), 27.62 (C, 1), 22.07 (CH2, 7), 20.00 (CH2, 10), 16.62 (CH3, 8), 13.60 (CH3,11 5H,12,13,14,15,16),6.14 (d,J = 5.7 Hz,1H,4a),6.10 (d,…”

“…Following our endeavor towards gold catalysis as key tool to the development of several methodologies to design original heterocyclic compounds, 11 we described recently the catalytic activity of the system IPrAuCl/NaBArF as an efficient and selective catalyst for the cycloisomerization reactions of light oxygen-tethered 1,6-enynes leading to 3-oxabicyclo [4.1.0]-hept-4-enes (Scheme 3). 12 The preliminary olfactory properties prompted us to develop this chemistry on novel substrates such as other ethers and thioethers in order to access other facets on fragrances wheel and to propose hypothesis on the structure-activity properties. Moreover, we discovered that the starting enynes had olfactory properties too and decided to make a full evaluation of all the families.…”

Indium-Catalyzed Cycloisomerization of 1,6-Cyclohexenylalkynes

“…1, x FOR PEER REVIEW 2 of 9 the case of the β-ketoester substrate containing the acetylene function [11][12][13]. We have also investigated the use of indium trichloride in alkyne activation for carbocyclization reactions by describing an efficient synthesis of exo-methylene α-disubstituted cyclopentane derivatives [14][15][16] and following our continuous work on gold catalysis [17][18][19][20][21], we wondered if we could promote cycloisomerization processes on cyclohexenylalkynes [22] in the presence of indium salts. These bicyclic derivatives are key building blocks and represent privileged scaffolds for biologically active molecules and natural products [23][24][25][26][27][28].…”