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 additions to enones 1 and 2, synthetic equivalents of the synthon 3, were studied using a variety of hydrocarbon dienes. The two enones have been shown to be effective and synthetically useful dienophiles. Spectroscopic (especially 1H and 13C magnetic resonance) and chemical techniques were used to define unambiguously the full structures of the adducts. The structures of the various reaction products were used to draw qualitative conclusions about the nature of the transition states involved and the various electronic and steric effects that play a role in the mechanistic course of the Diels–Alder reaction.

HSING-JANG LIU, TENG KO NGOOI, and ERIC N. C. BROWNE. Can. J. Chem. 66, 3 143 (1988). Under stannic chloride catalysis, 2-carbomethoxy-2-cyclohexen-I-one (5) was found to undergo Diels-Alder reaction with a variety of dienes to give directly the cis-1-octalone system possessing a functionalized substituent at the angular position. With unsymmetrically substituted dienes, the adducts were those predicted on the basis of the normal rules (orrho and para) governing the orientation of Diels-Alder addition. In cases where differing secondary orbital overlap would affect the stereochemistry of the adducts, the major isomer in each case was that produced by secondary overlap of the diene with the ester carbonyl rather than the ketone carbonyl, presumably due in part to a steric effect. The degree of stereoselectivity was further shown to be dependent upon both the reaction temperature and the diene used and was generally enhanced when the reaction was carried out at lower temperatures or when a bulkier diene was involved.HSING-JANG LIU, TENG KO NGOOI et ERIC N . C. BROWNE. Can. J. Chem. 66, 3143 (1988). On a trouvt que, sous I'influence d'une catalyse par le chlorure stannique, la carbomtthoxy-2 cyclohextne-2 one-1 (5) subit des rtactions de Diels-Alder avec un grand nombre de dienes pour conduire directement au systeme de l'octalone-1-cis posstdant un substituant fonctionnalist en position angulaire. Lorsqu'on effectue la rtaction avec des dienes qui ne sont pas substituts d'une fa~on symttrique, les adduits sont ceux que I'on peut prtvoir en se basant sur les regles normales (ortho et para) rtgissant l'orientation de l'addition de Diels-Alder. Dans les cas oh un recouvrement d'orbitales secondaires difftrent peut affecter la sttrtochimie des adduits, l'isomere principal obtenu est toujours celui provenant du recouvrement secondaire du ditne avec le carbonyle de I'ester plutbt qu'avec le carbonyle de la cttone; ce resultat est vraisemblablement dfi a un effet sttrique. On a dtmontrt que le degrt de sttrtostlectivitt dtpend aussi de la temperature de la rtaction ainsi que du diene utilist; on a remarqut qu'il augmente g~n%ralement lorsqu'on optre des temptraturG plus basses ou lorsqu'un diene plus encombrt est impliqut.[Traduit par la revue]

Diels–Alder addition of isoprene to enone-ester 3 proceeds exclusively to the para-addition product 6. The specificity of this route constitutes a significant improvement in the previously reported total synthesis of himachalenes via 6. The mechanistic significance of the observed specificity of addition is discussed.

Diels–Alder additions to keto ester 2 proceed in moderate to high yields with a variety of dienes under selected Lewis acid and thermal conditions. Thermal conditions provide the highest total yields for non-functionalized dienes, but Lewis acid catalysts, particularly stannic chloride, provide highly selective additions in greater net yields. A study of several functionalized dienes shows that zinc chloride is particularly effective in catalyzing additions to 2. No difference in stereoselectivity is observed between zinc chloride and thermal reactions for highly functionalized dienes. The significance of the regiochemical and stereochemical results of the Diels–Alder reactions is discussed.