Carvones reduction

Oosterhaven, K., Hartmans, K.J. and Huizing, H.J. (1993) Inhibition of potato Solanum tuberosum) sprout growth by the monoterpene S-carvone reduction of 3-hydroxy-3-methylglutaryl coenzyme A reductase activity without effect on its mRNA level. /. Plant Physiol., 14,1463-9. 

Dihydrocarveol, Cj H gO, is a natural constituent of caraway oil, and is also obtained by the reduction of carvone. 

The above values apply to natural dihydrocarveol from caraway oil. A specimen prepared by the reduction of carvone had a specific gravity 0-927 at 20° and refractive index 1-48168. i (r.ii4.j... 

By reduction carvone fixes 2 atoms of hydrogen on to the ketonic group, and 2 atoms in the nucleus, with the formation of dihydrocarveol, CijHjgO, whose corresponding ketone, dihydrocarvone, Cj Hj O, exists in small quantities in caraway oil. 

The reduction of piperitone to menthone cannot well be brought about by the action of sodium or of sodium-amalgam in alcoholic solution, because, with the latter particularly, a solid bimolecular ketone is formed at once. This is a finely crystallised substance, melts at 148° to 149° C., and has the formula C gHj O. Piperitone thus follows the rule with substances having a conjugated double bond, carvone for instance, also forms a bimolecular ketone on reduction, melting at 148° to 149° C. 

Epoxide (25) is needed as an intermediate for reductive alkylation. How would you make it from carvone (24) ... 

Table 3 summarizes the scope and limitation of substrates for this hydrogenation. Complex 5 acts as a highly effective catalyst for functionalized olefins with unprotected amines (the order of activity tertiary > secondary primary), ethers, esters, fluorinated aryl groups, and others [27, 30]. However, in contrast to the reduction of a,p-unsaturated esters decomposition of 5 was observed when a,p-unsaturated ketones (e.g., trans-chalcone, trans-4-hexen-3-one, tra s-4-phenyl-3-buten-2-one, 2-cyclohexanone, carvone) were used (Fig. 3) [30],... 

The carboxylic acid 150 (Scheme 10.15) was prepared from commercial (-)-carvone (68) via a chemoselective reduction of the terminal olefin using tris... 

A total synthesis of functionalized 8,14-seco steroids with five- and six-membered D rings has been developed (467). The synthesis is based on the transformation of (S)-carvone into a steroidal AB ring moiety with a side chain at C(9), which allows the creation of a nitrile oxide at this position. The nitrile oxides are coupled with cyclic enones or enol derivatives of 1,3-diketones, and reductive cleavage of the obtained cycloadducts give the desired products. The formation of a twelve-membered ring compound has been reported in the cycloaddition of one of the nitrile oxides with cyclopentenone and as the result of an intramolecular ene reaction, followed by retro-aldol reaction. 

The hydrogenation of the monoterpenes (—)- and (-l-)-carvone was studied extensively. Several microorganisms were used in these reductions. They catalyzed the production of all possible stereoisomers, but some of them only in small quantities. The distribution of the products depended on the catalyst applied116. 

In Yamada s retrosynthetic analysis (Scheme 11), elisabethin C (26) is traced back to lactone 64 which would be converted into 26 by deoxygenation and chain elongations. Key intermediate 64 could be obtained by a stereoselective Dieckmann cyclization. The required ester lactone precursor 65 would be accessible from 66 by a series of oxidation reactions. Further disconnection would lead to commercially available (+)-carvone (67). Stereoselective successive alkylation of 67 and reduction of the enone should deliver 66 [30]. 

The linear sequence starts from (-l-)-carvone (67) (Scheme 12). Establishing the quaternary center at Cl was achieved via a successive enolate alkyla-tion/hydroxyalkylation to furnish hydroxyketone 68. Reduction of the enone... 

An alternative, in situ source of (Ph3P)CuH can be fashioned from CuCl/PPhs/ TBAF and PhMe2SiH (1.2 equivalents) in DMA, initially made at 0° with the reaction then being run at room temperature [25]. Unhindered acyclic enones require 20 mol% of CuCl, PPhs, and TBAF for best results (Eq. 5.15). Cyclic examples are more demanding, with substituted cyclohexenones such as carvone undergoing reduction when excess reagents are present (1.6 equivalents). Acetylcyclohexene was unreactive to the catalytic conditions above. 

Literature examples include one-, two-, and three-step hydrogenation reactions, hi each case, the reactant and product concentrations were monitored, as were intermediates or side reaction products as necessary. Simple peak height or area measurements were sufficient to generate reaction profiles for the reduction of cyclohexene [116] and of l-chloro-2-nitrobenzene [117]. However, for more spectrally complex systems, such as the reduction of carvone and of 2-(4-hydroxyphenyl) propionate, multivariate curve resolution (MCR) was required [117]. 

Reduction of 0,/3-enones. NaBH4 forms a nearly homogeneous solution in pyridine at 25°. This solution reduces /-carvone (1) at 25° (12 hours) mainly to the dihydrocarveols 2. A minor product is 3. Jones oxidation of the mixture gives dihydrocarvone (4).1 This method was first reported by Kupfer.2... 

Nevertheless, in the hydrogenation of poly-unsaturated molecules the catalyst effects are more evident in the selectivity patterns, as is shown in Table 2 and 3. The selectivity behavior for the various catalysts, show that Rh/MgO is the most selective for carvotanacetone formation. The addition is mainly limited, in these catalysts, to one hydrogen molecule, although in carvone there are three possible sites at which reduction can occur. 

Regeneratable polymeric organotin dihydride beads have been used to reduce halides selectively (e.g. 3-bromocamphor to camphor).52 /3-Unsubstituted cyclohex-enones undergo exclusive and almost quantitative 1,4-reduction by potassium tri-s-butylborohydride to the corresponding saturated ketone [e.g. (16)] 53 reductive alkylation of carvone proceeds similarly to (17 R = Me, X = H).53 In contrast,... 

A Pseudomonas strain hydroxylates p-menthane to cis-p-menthan-l-ol,84 and microbiological reduction of carvotanacetone with Pseudomonas ovalis gives similar results85 to those obtained with carvone (Vol. 5, p. 24, incorrectly reports inversion at C-4). (—)-Carvotanacetone (30) gives (+)-carvomenthone (31), (—)-... 

Before the introduction of metal-ammonia solutions for the reduction of a,p-unsaturated carbonyl compounds,sodium, sodium amalgam, or zinc in protic media were most commonly employed for this purpose. Some early examples of their use include the conversion of carvone to dihydrocarvone with zinc in acid or alkaline medium, and of cholest-4-en-3-one to cholestanone with sodium in alcohol. These earlier methods are complicated by a variety of side reactions, such as over-reduction, dimerization, skeletal rearrangements, acid- or base-catalyzed isomerizations and aldol condensations, most of which can be significantly minimized by metal-ammonia reduction. 

In order to study the factors determining the regioselectivity of sodium borohydride reduction of a, -unsaturated ketones, reactions with 3-methylcyclohexenone, carvone and cholestenone were carried out in 2-propanol, diglyme, triglyme or pyridine. Mixtures of 1,2- and 1,4-reduction products were obtained in the alcoholic and ether solvents, whereas pure 1,4-reduction was observed in pyridine. Addition of triethylamine to NaBH4 in diglyme led to formation of triethylamine borine, EtsN BHs. Similarly, with pyridine, pyridine borine could be isolated, leading to exclusive 1,4-reductions. 

Of special interest are the relative rates of reduction of various cyclic enones, such as carvone, acetylcyclohexene and pulegone (Scheme 60). While the enone system in carvone is frozen in its transoid... 

Both naturally occurring enantiomers of carvone were selectively reduced by B. sulfurescens (Scheme 71). (-)-Carvone was reduced to (-h)-dihydrocarvone (trans) and further to (-H)-neodihydrocarveol, whereas (-i-)-carvone was reduced to (-)-isodihydrocarvone (cis), which was then converted to (-)-neo-isodihydrocarveol. Similar reductions with identical stereoselectivities were observed earlier with Pseudomonas ovalis (strain 6-1) and with a strain of Aspergillus niger. ... 

Di-hydro Carveol, Di-hydro Carvone.—Di-hydro carveol, the other important menthen-ol, is present in kummel oil, together with the corresponding ketone, di-hydro carvone, from which it may be obtained by reduction. This ketone is the di-hydrogen addition product of a mentha-di-ene ketone known as carvone which we shall presently consider. 

S)-(+)-carvone. The key steps were Baeyer-Villiger oxidation, Oppenhauer oxidation, Meerwein-Ponndorf-Verley reduction, a stereospecific Grignard addition, and an intramolecular Sn2 reaction. 

The tricyclic ring system containing the fully functionalized CD ring of taxol was prepared from (S)-(+)-carvone by T.K.M. Shing et al. The bicyclic a-hydroxy ketone (4-hydroxy-5-one) was isomerized by an Intramolecular redox reaction in the presence of catalytic amounts of aluminum isopropoxide. This example was a special case where both reactants were in the same molecule the ketone was the oxidant for the Oppenauer oxidation, whereas the secondary alcohol was the hydride donor for the MVP reduction. The conversion to the thermodynamically more stable 5-hydroxy-4-one proceeded in good yield. 

Alkylation of isovaleramide with 1,3-dichlorobut-2-ene yields (139) after methyl-ation acid-catalysed hydrolysis and internal aldol condensation gives ( )-piperitone. The value of piperitenone and isopiperitenone formation, probably via electrocyclic reaction of the pyrolytic acetic acid-elimination product from A - and A -isomers of (49), cannot be assessed in the absence of reaction yields. (S)-(-)-Pulegone is obtained in good yield from (- )-citronellol by oxidation with pyridinium chlorochromate followed by double-bond isomerization. Low-temperature reduction of ( —)-carvone to ( —)-cz5-carveol (140) and... 

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