Internal Nucleophilic Termination in Acid‐Mediated Polyene Cyclisations: Synthetic access to methyle homologs of (±)‐Ambrox® and its diastereoisomers

Abstract

(16.111.93)Treatment of ten monocyclic dienols 8-11 with an excess of fluorosulfonic acid in 2-nitropropane at -90" afforded diastereoisomeric mixtures of racemic tricyclic ethers 12-14 in 81-91 % yield (see Tables I and 2). These transformations represent further examples of biomimetic acid-mediated cyclisations in which an OH group serves as the internal nucleophilic terminator. A non-synchronous process is postulated, and the examples described strongly re-inforce our working mechanistic hypothesis, whereby the stereochemical course of cyclisation is directed by the orientation of the side chain vicinal to the intermediate cyclohexyl cation (see Schemes 4 and 5 ) . It is also demonstrated that the efficiency of this process is independent of the nature of the OH group, which may be primary, secondary, or tertiary. In addition, the organoleptic properties of 12-14, Me homologs of known odorants such as Ambroxs ((-)-3a) and its diastereoisomers, are briefly discussed.Introduction. -Recently, we described an efficient biomimetic access to organoleptically active tricyclic ethers, by treatment of appropriately substituted 6-(cyclohexenyl)hex-3-en-1-01s with an excess of fluorosulfonic acid in 2-nitropropane at -90" [ 11. These kinetically controlled cyclisations') were shown to proceed stereospecifically via protonation of the cyclohexenyl bond, followed by ring closure involving equatorial C-C bond formation with concomitant internal nucleophilic termination by anti-addition of the OH group across the C(3)=C(4) bond. For example, allowing for partial acidcatalysed isomerisation of the C(3)=C(4) bond, (E)-and (Z)-l selectively afford 3a and 3b, whereas (E)-and (2)-2 preferentially generate 3c and 3d, oiu a favoured chair

Enzyme-like polyene cyclizations catalyzed by dynamic, self-assembled, supramolecular fluoro alcohol-amine clusters

“…Since then, multiple publications have appeared offering access to a plethora of sophisticated structural terpene motifs, many of them arising from a protonation-assisted cyclization. However, when following the natural pathway, linear polyenes have to be treated with strong organic or inorganic Brønsted or Lewis acids such as trifluoroacetic acid 16 , fluorosulfonic acid [17][18][19][20] , SnCl 4 21-25 , BF 3 •OEt 2 26-28 , RuCl 3 29-31, and In(III) salts 30,32 , mostly under cryogenic conditions, to allow for productive ring closure. These synthetic methodologies suffer from several general drawbacks, including moderate diastereoselectivities and low functional group tolerance that overall lead to a narrow substrate scope [33][34][35] .…”

“…Since then, multiple publications have appeared offering access to a plethora of sophisticated structural terpene motifs, many of them arising from a protonation-assisted cyclization. However, when following the natural pathway, linear polyenes have to be treated with strong organic or inorganic Brønsted or Lewis acids such as trifluoroacetic acid 16 , fluorosulfonic acid [17][18][19][20] , SnCl 4 21-25 , BF 3 •OEt 2 26-28 , RuCl 3 29-31…”

Superacid‐Catalyzed Reactions

“…810,811 The stereospecific product formation is rationalized by synchronous internal anti-addition via chair-like conformations of the protonated cyclohexene ring, resulting in ring closure with equatorial CÀC bond formation and concomitant internal nucleophilic termination by anti-addition of the OH group [Eq. 810,811 The stereospecific product formation is rationalized by synchronous internal anti-addition via chair-like conformations of the protonated cyclohexene ring, resulting in ring closure with equatorial CÀC bond formation and concomitant internal nucleophilic termination by anti-addition of the OH group [Eq.…”

Ambergris: perfume e síntese

“…Dos produtos de partida mais utilizados nestas ciclizações catalisadas por ácido estão a geranilacetona (17) 32 e a dihidro-βionona (39) 51,52,53 , obtida pela hidrogenação da β-ionona com hidreto de terc-butil estanho e AIBN catalítico. Em 1992, Snowden 45 propôs a síntese do (±)-ambrox e seus diastereoisômeros, pela ciclização biomomética de 17 e 39 (Esquema 6).…”