Carvone stereochemistry

Further details of the photoaddition of N-nitrosopiperidine to a-pinene have been published.The claim of a-fenchen-6-one oxime formation (Vol. 7, p. 43) has been retracted the product is optically active carvone oxime. The stereochemistry and conformations of amino-oximes derived from a-pinene nitroso-chloride have been examined. ... 

The structure of 5-isothiocyanatopupukeanane (257), a sesquiterpene isothiocyanate from an Axinyssa species from Guam, was determined by X-ray analysis [260]. Two isomeric sesquiterpene thiocyanates, 2-thiocyanatoneopupukeanane (258) and 4-thiocyanatoneopupukeanane (259) were isolated from an unidentified sponge from Pohnpei and from Phycopsis terpnis from Okinawa [261]. A sample of Axinyssa (= Trachyopsis) aplysinoides from Palau yielded a rare thiocyanate, 2-thiocyanatopupukeanane (260), while two specimens from Pohnpei yielded 13-isothiocyanatocubebane (261), 1-isothiocyanatoaromadendrane (262) and 2-thiocyanatoneopupukeanane (258) [262]. This last compound had previously been assigned different stereochemistry at C2 [261]. (-)-4-Thiocyanatoneopupukeanane has been synthesised in an enantiospecific manner (259) [263]. Both enantiomers of 2-thiocyanatoneopupukeanane (258) have been synthesised from (7 )-carvone [264]. 

These reactions may show considerable selectivity. Corey and Chaykovsky19 give an example with the terpene carvone 80. The ylid 78 is made with NaH and reacts only with the enone and not with the unconjugated alkene. The product is one diastereoisomer 81 as the ylid has added to the opposite side of the ring to the only substituent. It also has retained the stereochemistry of the cis alkene but that is inevitable as 3/6 ring fusion must be cis. 

Since initially neither the stereochemistry of the trisub-stituted double bond nor the absolute configuration of component XVI was known, we prepared all four of the possible geometric and optical isomers starting from either (J3)-(+)-carvone (Figure 6) or (R)-(-)-carvone, and only the 3Z,6R isomer was found to be attractive to the males (48). This is not a practical route to XVI a shorter synthesis of racemic XVI was subsequently published by Still and Mitra (51). 

The reaction of racemic 147 with (R)-carvone, initially at -78 °C followed by warming to room temperature for 1 h, gave the vinylcyclopropane 151 in 72% yield and moderate diastereoselectivity (d.r. = 75 25). The stereochemistry of the major diastereoisomer shown in structure 151 from H NMR studies was that expected based on the stereochemical outcome of the reaction of racemic 147 with the achiral cyclic enones 146 and is consistent with our previously proposed chelated transition state90 for cyclic enones (compare with the transition state B). 

Other papers related to p-menthanes concern vinylaziridine formation from pulegone oxime and from carvone-NN-dimethylhydrazone methiodate,234 non-ozonolytic cleavage of 10-trichloromethyl-limonene,235 and the stereochemistry of 1-chloro-l-nitroso-p-menthanes236 and of dihydropinol rearrangements (cf. Vol. 2, p. 34).237... 

A recent enantiospecific synthesis of (-)-nupharamine (243), (+)-3-epinupharamine (244), (-)-anhydronupharamine (245) and (-)-nuphenine (246) has been reported, starting with either (+)- or (-)-carvone [541]. In this synthesis, a key acyclic precursor with the required stereochemistry was produced via regioselective fragmentation of a y-halo-ester, and the piperidine ring was formed using an aza-Wittig reaction. 

The use of (trimethylsilyl)allenes in a (trimethylsilyl)cyclopentene annulation was described in Section 1.6.1.2.3.1 and was shown to occur with a number of electron-deficient olefins6. The following example illustrates the extent to which stereochemistry in the olefinic acceptor can influence the course of the addition. Thus, in the addition to carvone, one diastereomeric product is obtained as a result of attack by the silylallene on the face of the double bond opposite to the isopropenyl unit. 

Absolute Configuration of (+)>Bottrospicatoi (10). To determine the stereochemistry, synthesis of (+)-bottrospicatol and isobottrospicatol (Cg-epimer) was carried out according to Figure 4. (-)-Carvone (1) was oxidized by m-chloroperbenzoic acid in dry ether to give the diastereomixture of 8,9-epoxycarvone (85%), colorless oil ... 

Having reviewed the principles of stereochemistry, we are now in a position to investigate the chemistry of mint. There are many species and sub-species of mint and their chemistry is dominated by monocyclic monoterpenoids, mostly alcohols and ketones. Some of the more important ones are shown in Figure 4.9. By far the most important of these are carvone and menthol, both of which will be discussed in more detail later. 

FIGURE 19.117 Stereochemistry in the reduction of (-)-carvone (93 ) by the reductase from Euglena gracilis Z. (Modi ed from Shimoda, K. et ah, Phytochemistry, 49, 49,1998.)... 

In contrast, almost all the yeasts tested showed reduction of carvone, although the enzyme activity varied. The reduction of (-)-carvone (93 ) was often much faster than the reduction of (+)-carvone (93). Some yeasts only reduced the carbon-carbon double bond to yield the dihydrocar vone isomers (101a and b and 101a and b) with the stereochemistry at C-1 with / -con guration, while others also reduced the ketone to give the dihydrocarveols with the stereochemistry at C-2 always... 

An -ray structure determination of a cationic intermediate (8) isolated during the acylation of [Fe(CO)8(rraAw, ra j-hexa-2,4-diene)] establishes that Friedel-Crafts acylation involves stereospecific endo attack. The stereochemistry of reaction parallels protonation of tricarbonyl(diene)iron, cyclopentadienyl(cyclohexa-l,3-diene)rhodium complexes, and ( j -cyclopentadienyl)rhodium complexes of limonene (9), a-phellandrene (10), and carvone (11). ... 

IR, 3R, 4S) which occurs in peppermint oil, has a clean sweet, cooling and refreshing peppermint aroma, while in the d-form (IS, 3S, 4R) it has remarkable, disagreeable notes such as phenolic, medicated, camphor and musty. Carvone (XXI in Table 5.33) in the R(—)-form has a peppermint odor. In the S(+)-form it has an aroma similar to caraway. Other examples that show the influence of stereochemistry on the odor threshold of terpenes are 3a,4,5,7a-tetrahydro-3,6-dimethyl-2(3H)-benzofuranone (cf. 5.2.5) and 1-p-menthene-8-thiol (cf. 5.3.2.5). 

Carvone, also known as p-mentha-6,8-dien-2-one and carvol, is a material of commercial importance and has been reviewed by Clark (310). There are two enantiomers of which the (/ )-( )- is the commoner and is used in much greater quantities. If the stereochemistry is not specified, it is usually the (/ )-(—)-enantiomer, usually referred to as /-carvone, which is intended. Both isomers occur fairly widely in essential oils. The most significant natural sources of carvone are spearmint, dill, and caraway. The term spearmint is applied to various Mentha species including M. cardiaca, M. gracilis, M. spicata, and M. viridis and these usually contain 55-75% of the (/ )-( )-enantiomer (242). The (5)-(+)-enantiomer (243) is found in diU (Anethum graveolens) at levels of 30-65% and at 50-75% in caraway (Conan carvi). 

FIGURE 7 The infamous bottle of carvone, now inscribed with the right stereochemistry. 

Females of the California red scale (Aonidiella aurantii) release a mixture of the branched unsaturated acetates (332a) and (333) to attract males. Synthesis of the R,Z component (332a) was achieved by Roelofs et al. 74, 75) starting from (5 -(+)-carvone (321) (Scheme 59). The final product consisted of a mixture of the Z and E isomers, which were easily separable by GC. The absolute stereochemistry of the 3-methyl group in (333) is unknown. 

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