Total synthesis of α- and β-himachalene by an intermolecular Diels–Alder approach

Abstract

HSINGJANG LIU and ERIC N. C. BROWNE. Can. J. Chem. 59,601 (1981). A total synthesis of a-himachalene (2) and P-himachalene (3) has been achieved in eleven steps and in an effective overall yield of 21% from 4,4-dimethyl-2-cyclohexenone (4). The synthesis involves keto ester 7 as a key intermediate which is conveniently prepared by the Diels-Alder addition of dienone ester 6 to isoprene.HSING-JANG LIU et ERIC N. C. BROWNE. Can. J. Chem. 59,601 (1981). Partant de IadimCthyl-4,4 cyclohexene-2 one (4) on arCalisC, en 11 Ctapes et avec un rendement gIobal de 21%, une synthese totale de I'a-himachalkme (2) et de la P-himachalkme (3). La synthese fait appel a un intermkdiaire clC, le dtoester 7, qui est prCparC avec facilite par une addition de Diels-Alder de I'ester diCnone 6 sur I'isoprene.[Traduit par le journal]The himachalane carbon skeleton (1) is characteristic of a growing class of sesquiterpenes (1-13). The isolation of two representatives of the class was first reported by Dev and co-workers in 1952 from the essential oil of the Himalayan cedar (Ced-, rus deodara Loud) (1). The gross skeletal structure of the two new hydrocarbons, designated a -and P-himachalene, was reported almost simultaneously in 1961 by Joseph and Dev (2) and by Bredenberg and Erdtman (3) who isolated the two compounds from Atlas cedar (Cedrus atlantica) and from Cedrus libani. In 1968 Joseph and Dev were able to rigorously establish the structure (4) and the absolute stereochemistry (5) of a-himachalene as 2 and of P-himachalene as 3. These two natural hydrocarbons have been the subject of considerable synthetic activity and several total syntheses have been accomplished during the last decade (14-17). We wish to report a fundamentally different approach to the synthesis of a-(2) and P-himachalene (3) in racemic form.Our synthetic plan called for two critical operations, the construction of a suitably functionalized 4,4-dimethyl-1-decalone derivative (i.e. 16) and a one-carbon ring enlargement (i.e. 16 + 17). The former process was facilitated by a Diels-Alder approach using 2-carbomethoxy-4,4-dimethyl-2,5-cyclohexadienone (6) as a dienophile. The initial studies (18) on the addition of isoprene to dienone ester 6, readily prepared from 4,4-dimethyl-2-cyclohexenone (4) by carbomethoxylation (4 + 5) followed by oxidation with selenium dioxide, employed boron trifluoride etherate as a catalyst. The reaction, carried out at room temperature in ether, resulted in the formation of what appeared to be a single adduct which showed homogeneity on tlc and four methyl singlets in the 4 R = H 6 5 R = COOCH, 'Hmr spectrum, and to which structure 7 was assigned based on the well established rules governing the Diels-Alder reaction (19). However, further examination of the adduct by 13Cmr revealed that it was in fact a mixture of two compounds (thirty carbon signals). Separation of these two compounds was possible by preparative high-pressure liquid chromatography. Surprisingly, the major component, which amounted to 70% of the mixture, was the undes...

Diels–Alder reactions of 4,4-dimethyl-2-cyclohexenones. A direct route to the 4,4-dimethyl-1-decalones

“…We have previously reported (33,35,36) briefly on the dienophilic character of the two enones 1 and 2 and we wish now to elaborate on the full scope of our work in this area and to comment on the mechanistic and spectroscopic aspects of the results.…”

On the structure of the adduct from the aluminium chloride catalyzed Diels–Alder reaction of 2-methyl-2-cyclohexenone with isoprene

“…The '~m r spectra were recorded on a Varian HA-100, Bruker WH-'Hmr spectrum of this compound displayed a signal due to a 200, or WH-400 spectrometer and, except where otherwise stated, peri-proton (c-8 H) (6,8,9) as a doublet ( J = 8 H~) at 6 7.92.…”

An intermolecular Diels–Alder approach to (±)-isoacanthodoral

“…During the course of our synthetic studies on himachalenes (6), the Diels-Alder reaction of 2-carbomethoxy-4,4-dimethyl-2,5-cyclohexadienone (4)4 and isoprene was investigated. Interestingly, under boron trifluoride catalysis, the cycloaddition gave mainly the abnormal anti-para adduct 7 (64% yield) along with a small amount (28% yield) of the expectedpara adduct 8.…”

“…To reduce the enone moiety, compound 7 was treated with triethylsilane in the presence of tris(tripheny1phosphine)rhodium(1) chloride (Wilkinson's catalyst) (6,7). The silyl en01 ether 9 thus obtained in 97% yield was subsequently hydrolyzed with aqueous potassium bicarbonate in methanol to give crystalline keto ester 10 (mp 4142°C) in quantitative yield.…”

“…The silyl en01 ether 9 thus obtained in 97% yield was subsequently hydrolyzed with aqueous potassium bicarbonate in methanol to give crystalline keto ester 10 (mp 4142°C) in quantitative yield. For the 4~h i s compound was previously prepared from keto ester 5 via selenium dioxide oxidation (6). An improved procedure has since been developed, involving bromination of 5 with N-bromosuccinimide followed by dehydrobromination of the resulting bromide 6 with For personal use only.…”