Terpenic ketones, preparation

Compounds with carbon-nitrogen multiple bonds were also successfully used in the Barbier procedure. Allylic groups add to imines in high yields (> 77% in the examples published), even enolizable substrates, possibly due to the low basicity of the medium.37 Additions to nitriles occur in THF in the presence of the zinc-silver couple.38 Terpenic ketones were prepared by this method. 

Camphene is a solid terpene. The dextro variety d-camphene is found in camphor, ginger and spike oils, and the levo variety, 1-camphene is in citrondla and valerian oil and in French and American turpentine. Bornylene does not occur in nature but has been prepared from the alcohol corresponding to it known as Borneol or Borneo camphor. This, as previously stated, may be prepared from pinene so that Bornylene itself may be made from pinene. Fenchene, also, is not found in nature but is obtained by reduction of fenchone a terpene ketone found in fennel oil and in Thuja oil. 

The Robinson annulation is a valuable method for preparing bicyclic and tricyclic structures that can serve as starting materials for the preparation of steroids and terpenes.175 Reaction with 2-methylcyclohexan-l,3-dione gives a compound called the Wieland-Miescher ketone. 

Some representative Claisen rearrangements are shown in Scheme 6.14. Entry 1 illustrates the application of the Claisen rearrangement in the introduction of a substituent at the junction of two six-membered rings. Introduction of a substituent at this type of position is frequently necessary in the synthesis of steroids and terpenes. In Entry 2, formation and rearrangement of a 2-propenyl ether leads to formation of a methyl ketone. Entry 3 illustrates the use of 3-methoxyisoprene to form the allylic ether. The rearrangement of this type of ether leads to introduction of isoprene structural units into the reaction product. Entry 4 involves an allylic ether prepared by O-alkylation of a (3-keto enolate. Entry 5 was used in the course of synthesis of a diterpene lactone. Entry 6 is a case in which PdCl2 catalyzes both the formation and rearrangement of the reactant. 

L-699,392, Merck s drug for the treatment of chronic asthma, is an example of asymmetric amplification on an industrial scale (see Figure 13.19). The ketone reduction can be carried out stoichiometrically with a borane-(-)-a-pinene reagent. The terpene natural products are often mixtures of isomers and enantiomers. A reagent prepared from 98% optically pure (-)-a-pinene gives a product e.e. of 97%, but a reagent prepared from less expensive 70% optically pure (-)-a-pinene yields a product e.e. of 95%, which can be pushed to >99.5% by using an excess [30]. 

The product in entry 1 of Scheme 2.10 is commonly known as the Wieland-Miescher ketone and is a useful starting material for the preparation of steroids and terpenes. The Robinson annulation to prepare this ketone can be carried out enantioselectively by using the amino acid L-proline to form an enamine intermediate. The 5-enantiomer of the product is obtained in high enantiomeric excess.89 This compound and the corresponding product obtained from cyclopentane-1,3-dione90 are key intermediates in the enantiose-lective synthesis of steroids.91... 

Other Peroxyacids. Benzeneperoxyseleninic acid has been prepared in situ from benzeneseleninic acid and hydrogen peroxide and is used to epoxidize terpenic olefins and Baeyer-Villiger oxidation of cyclic ketones. 

Spices impart aroma, colour and taste to food preparations and sometimes mask undesirable odours. Volatile oils give the aroma, and oleoresins impart the taste. Aroma compounds play a significant role in the production of flavourants, which are used in the food industry to flavour, improve and increase the appeal of their products. They are classified by functional groups, e.g. alcohols, aldehydes, amines, esters, ethers, ketones, terpenes, thiols and other miscellaneous compounds. In spices, the volatile oils constitute these components (Zachariah, 1995 Menon, 2000). 

Woodgate et al. [51] applied the C-H/acetylene coupling to the ortho-selective alkenylation of terpene derivatives (Eq. 27). The basic feature of this reaction is the same as the alkenylation reaction of Murai et al. The combination of acetophenone and diynes provides a new entry for the copolymerization of aromatic ketones with acetylenes. Weber et al. [50] studied extensive reactions of ruthenium-catalyzed C-H/acetylene coupling with respect to the step-growth copolymerization of aromatic ketones and acetylenes (Eq. 28). These coupling reactions provide a new route to the preparation of trisubstituted styrene derivatives. 

Unsymmetrical alkenes can be prepared by mixed intermolecular reactions if one of the components, commonly acetone, is used in excess (equation 83). As the isopropyl group is a common subunit of many terpenes this method provides a valuable route for its introduction. Pattenden and Robertson used such a reaction followed by a Grob-type fragmentation in their preparation of the daucenone (42) from the readily enolized ketone (43). The bicycle (42) was used as an intermediate for the synthesis of the diterpene ( )-isoamijiol (44 equation 84). Mixed couplings are not restricted to acetone, and almost any carbonyl may be used. For example, Paquette et al. employed the aldehyde (45) in a synthesis of ( )-a-vetispirene (46 equation 85). More complex mixed couplings are also possible. For example, the aldehydes (47) and (48) are coupled efficiently to the stilbene (49), which in turn is converted to phenan-threne alkaloids such as atherosperminine and thalictuberine (equation 86). ... 

In two further applications to terpene chemistry the bicyclic ketone 59, a model system for the preparation of cyclopentanoid terpenes, has been pyrolyzed under different conditions. ... 

It was found that the rate of the reaction and selectivity towards formation of 4 could both be increased by dealumination of the outer surface of the zeolite with Na2H2EDTA. When the solvent was changed to pure acetone a new compound (5) was formed. In this study, the coupling of ketones (acetone, butanone, and cyclohexanone) with 1 was found to be catalyzed solely by zeolite beta. The reaction also seems to be exclusive to a-pinene, because no reaction occurred when other terpenes such as 3, 4, and borneol (6) were used in place of a-pinene. It is also worth noting that borneol (6) has also been prepared from 1 by use of a high-silica zeolite [14],... 

The Wieland-Miescher ketone (1) can be commercially obtained or prepared [1,2] in the laboratory. Its methyl analog (2) is probably not commercially available but can be prepared in the laboratory by the published procedure [3,4]. The aim of the present review is to describe briefly the synthesis of several bioactive terpenes from these ketones (1) and (2). It describes only the synthesis (total and formal) of bioactive di-and sesquiterpenes. It is necessary to mention that the review does not claim to include the synthesis of all bioactive terpenes from the above mentioned ketones. 

P,7-Unsaturated ethers of cyanohydrins, on formation of lithio derivatives, undergo a 2,3-sigmatropic rearrangement to form. y-unsaturated ketones (equation 21), whereas benzylic ethers of aliphatic cyanohydrins gave o-methylaryl ketones. The method has been used to prepare 3-methyi-l-(3-methyl-2-furyl)-l-butanones, a naturally occurring Cio terpene, a-allenic ketones and enolic monoethers of 7-keto aldehydes via 2,3-sigmatropic rearrangement of tiieir respective carbanions. ... 

Thujone was discovered by E. Schweizer. C. VolckeP discovered carvone in carraway seed oil, and cineol in wormseed oil. Carvone was shown to be a ketone related to limonene by H. Goldschmidt and R. Ziirrer. Linalool was discovered by distilling coriander oil by A. Kawalier and prepared from linaloe wood (licari kamali) by H. Morin.Geraniol was discovered by O. Jacobson in oil of palma rosa. F. W. Semmler " showed that it is an olefinic terpene with an open carbon chain. Menthone was obtained from oil of peppermint by R. W. Atkinson and H. Yoshida. (Menthol was known much earlier and was analysed by Dumas in 1832.) G. Bouchardat and R. Voiry obtained terpineol from essential oils. Citronellal (an aldehyde) was discovered by F. D. Dodge.2 ... 

Natural waxes can consist of a wide range of different lipid classes, including esters of various kinds, hydrocarbons, ketones, hydroxy-ketones, p-diketones, aldehydes, acids and terpenes. With cmde mixtures of this kind, it is usually necessary to react them with diazomethane to methylate free carboxyl groups, to acetylate (or to prepare TMS... 

Putrefied animal matter hcis formed the basis for coyote attractants of possible value in pest control programs. Thus, a putrefied fish formulation has been used as a coyote lure and, more recently, attention has been directed to a fermented aqueous suspension of chicken whole-egg powder, developed initially as an attractant for flies (48). The odor components csf this material have been subjected to detailed chemical analysis ty Bullard et al. (49) and are reported to include volatile fatty acids (77% total 13 acids identified), bases (13% total, mainly trimethylamine, 9 amines identified), and headspace volatiles, including esters, aldehydes, ketones, alcohols, alkyl aromatics, terpenes and sulfur compounds (10% total, 76 compounds identified). Based on these data, a synthetic mixture, "synthetic fermented egg" has been formulated, composed largely of a mixture of ten volatile fatty acids (81%), together with a diverse range of amines and other compounds (50). This mixture was found to be as attractive to coyotes as the fermented preparation itself. The volatile fatty acid component alone was found to exhibit substantial coyote attractancy also (50,51). ... 

The reaction of (16) under photochemical conditions led to (17) by ring opening and carbonyl insertion. Conjugation may occur, forming the cyclohexenone (18) (eq 7). The expansion of the carbon skeleton of terpene hydrocarbons via carbonylation offers an interesting means to prepare optically active strained ketones (eq 8). ... 

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