This account corresponds to the presentation given by the main author on the occasion of the 2nd Swiss Industrial Symposium in Basel (October 19th , 2018). After a short historical introduction to methyl-jasmonate and methyl-epijasmonate, it essentially focuses on the reported more promising industrial approaches devoted to the synthesis of these naturally occurring odorants isolated from jasmine flowers. Some attempts to simplify these approaches, as well as independent unreported strategies are also presented. Several asymmetric methodologies are also discussed such as Xie hydrogenation, Corey-CBS reduction, enzymatic resolution, and 1,4-addition.
Dedicated to Dr. G¸nther Ohloff on the occasion of his 80th birthday Only one out of the four possible trans isomers of the important perfumery alcohol Norlimbanol ¾ (1) possesses a very strong amber-woody smell, the isomer 1A with (1'R,3S,6'S) absolute configuration. Its enantiomer 1B is almost odorless and devoid of amber-woody character, whereas the diastereoisomers 1C and 1D are considerably weaker and perceptible only by the most-sensitive persons. The same is true for a whole series of perceptual analogs of 1, including b-alkoxy alcohols. These ethers belong to two structural classes: [(2,2,6-trimethylcyclohexyl)oxy]-(see 3, 4, and 16) or {[2-(tert-butyl)cyclohexyl]oxy}alkan-2-ol derivatives (see 19 and 20; Table). A superimposition model allowing for good overlap of the respective hydroxylated side chains offers a tentative explanation for the shared perceptual characteristics of the two classes (Fig. 5). The lipophilic cyclohexane moieties present only a minimal overlap in this model, suggesting that quite larger molecules might possess the same smell. (S)-Configured b-alkoxy alcohols can conveniently be obtained on a larger scale by enantioselective reduction of the corresponding ketones (Scheme 9).
1 1.IV.88) ~ ~ ~ ~ ~~~ ~ Citronella1(1) has been transformed into enol acetates 2 which have been cyclized with various Lewis and Briin.rlrd acids to dihydrocyclocitral (4). Application of this methodology to the synthesis of mono-and bicyclic ring systems has been examined.Introduction. -Cationic olefin cyclizations have been widely utilized for the synthesis of terpenes and other naturally occurring ring systems. Cyclizations initiated by protonation of trisubstituted double bonds have been terminated by a variety of functional groups such as alkyl-, aryl-, carboxyl-, 0-, F-, or (trialkylsily1)-substituted double bonds or alkynes [I]. In this communication, we report the use of aldehyde enol acetates as cationic cyclization terminators for the preparation of monocyclic and bicyclic terpenoids and similar ring systems.Aldehyde enol esters are attractive as cationic olefin cyclization terminators for several reasons. Aldehydes are easily, under mild conditions, transformed into enol esters, normally as (E/Z)-isomeric mixtures [2]. Ketones can also be transformed into enol esters, although under more stringent conditions, and be employed in cationic cyclization reactions [3]. However, regioselective ketone enol ester formation is often difficult to obtain. Cyclization of an aldehyde enol ester followed by aqueous workup again yields an aldehyde, which can be used in further synthetic manipulations. Thus, this scheme permits the formation of a C-C bond via cationic cyclization with retention of a heterofunctionality in a predictable manner.Results and Discussion. -Treatment of citronella1 (1) with a mixture of Ac,O, Et,N, and KOAc at 120" for 4 h followed by distillation furnished routinely enol acetates 2 ( ( E / Z ) 2:l) in 80% yield (cf Scheme). A third product identified as the diacetate 3 was also formed in 3-6% yield. Enol acetates 2 underwent acid-induced cyclization to dihydrocyclocitral(4) with a variety of Lewis and Bronsted acids (cf Table).The similar reactivity of Lewis and Bronsted acids was at first surprising until we observed that reactions with Lewis acids were much faster in the presence of a small amount of H,02). Under stringently dry conditions, the Lewis-acid-catalysed cyclizations were much slower and lower yielding. Catalytic amounts of Lewis acid as opposed to ')
Highly exo-selective [4+2] cycloadditions of cyclopenta-1,3-diene 2a to α,β-dialkyl conjugated enals 5 are compared with the analogous endo-favored Diels-Alder reaction of cyclohexa-1,3-diene 7. The exo-stereoselectivity is lower in the homologous case of methylcyclopenta-1,3-diene 9. This diastereoselectivity is discussed either in terms of a retro-homo-Diels-Alder reaction, associated with thermodynamic control, or with respect to either a competing hetero-Diels-Alder/Claisen or Cope domino pathway, or retro-Claisen/retro-hetero-Diels-Alder of the endo-homo-cycloadducts. These hypothetical mechanisms have been examined by DFT calculations at the MPW1K(CH2 Cl2 )/6-31+G** level of theory for the AlCl3 -mediated cycloadditions of 5d to 2a and 7. Application of Corey's methodology to the γ-halogeno-α-methyl-substituted dienophiles 5a and 5b allowed an enantioselective preparation of known and useful intermediates for the synthesis of either the naturally occurring (-)-β-santalol or its potentially olfactive structural analogs.
Acidic cyclization of either the diethylallylamines 29b or 30, followed by a 1.5 mol‐% Pd‐catalyzed carbomethoxylation of quaternized 31b, leads to the methyl ester 36a. This latter could also be obtained in optically pure form by carbomethoxylation of the corresponding (+)‐acetate. Final reduction‐cyclization may be conducted as earlier described, towards the desired odoriferous rac‐Ambrox® 38a, or its pure (−)‐enantiomer. Generation of a π‐allyl Pd complex from an allylic ammonium salt, followed by carboalkoxylation is novel. In only five chemical steps starting from farnesene 2, the present work constitutes the most concise total synthesis of rac‐Ambrox® 38a to date.
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