Limonene synthesis

Among chiral dialkylboranes, diisopinocampheylborane (8) is the most important and best-studied asymmetric hydroborating agent. It is obtained in both enantiomeric forms from naturally occurring a-pinene. Several procedures for its synthesis have been developed (151—153). The most convenient one, providing product of essentially 100% ee, involves the hydroboration of a-pinene with borane—dimethyl sulfide in tetrahydrofuran (154). Other chiral dialkylboranes derived from terpenes, eg, 2- and 3-carene (155), limonene (156), and longifolene (157,158), can also be prepared by controlled hydroboration. A more tedious approach to chiral dialkylboranes is based on the resolution of racemates. /n j -2,5-Dimethylborolane, which shows excellent enantioselectivity in the hydroboration of all principal classes of prochiral alkenes except 1,1-disubstituted terminal double bonds, has been... 

There seems no room for doubt that the above formula for ortho-limonene is the correct formula for limonene, and the classical synthesis of dipentene by W. H. Perkin, Jun., and his colleagues has proved beyond doubt that it is the correct formula for dipentene or i-limonene. 

Terpineol (that is a-terpineol) has been prepared synthetically by Perkin and his pupils, his method being described under the synthesis of limonene. 

The activity of the FePeCli6-S/tert-butyl hydroperoxide (TBHP) catalytic system was studied under mild reaction conditions for the synthesis of three a,p-unsaturated ketones 2-cyclohexen-l-one, carvone and veibenone by allylic oxidation of cyclohexene, hmonene, and a-pinene, respectively. Substrate conversions were higher than 80% and ketone yields decreased in the following order cyclohexen-1-one (47%), verbenone (22%), and carvone (12%). The large amount of oxidized sites of monoterpenes, especially limonene, may be the reason for the lower ketone yield obtained with this substrate. Additional tests snggested that molecular oxygen can act as co-oxidant and alcohol oxidation is an intermediate step in ketone formation. 

The enantioselective synthesis in Scheme 13.22 is based on stereoselective reduction of an a, (3-unsaturated aldehyde generated from (—)-(.V)-limonene (Step A). The reduction was done by Baker s yeast and was completely enantioselective. The diastereoselectivity was not complete, generating an 80 20 mixture, but the diastere-omeric alcohols were purified at this stage. After oxidation to the aldehyde, the remainder of the side chain was introduced by a Grignard addition. The ester function... 

Scheme 56 summarizes Mori s synthesis of (S)-vesperal (38), the female sex pheromone of the longhorn beetle (Vesperus xatarti) [85]. (F)-Limonene yielded (S)-38 by utilizing organoselenium chemistry. 

Selenium dioxide is also an oxygen donor to alkenes. In this case, however, the initial reaction of the double bond is with the selenium center followed by two pericyclic steps. After hydrolysis of the organo-selenium intermediate, the result is a hydroxylation at the allylic carbon position65. Thus, limonene (2) yields racemic p-mentha-l,8(9)-dien-4-ol66. The high toxicity of selenium intermediates and prevalence of many rearrangements has limited the widespread use of the reagent in synthesis. 

Terpenes Terpenes [a-pinene (1), /f-pinene (2), and limonene (3)] are employed in the synthesis of flavors and fragrances (F F), although these compounds are often obtained by catalytic routes from hydrocarbons. 

Both uncalcined and calcined LDHs have also been shown to be effective supports for noble metal catalysts [18-25]. For example, palladium supported on Cu/Mg/Al LDHs has been used in the liquid phase oxidation of limonene [24], and on calcined Mg/Al LDHs for the one-pot synthesis of 4-methyl-2-pentanone (methyl isobutyl ketone) from acetone and hydrogen at atmospheric pressure [25]. In the latter case, the performance depends on the interplay between the acid-base and hydrogenation properties. More recently. 

Another illustration of the use of such a biocatalytic approach was the synthesis of either enantiomer of a-bisabolol, one of these stereoisomers (out of four) which is of industrial value for the cosmetic industry. This approach was based on the diastereoselective hydrolysis of a mixture of oxirane-diastereoiso-mers obtained from (R)- or (S)-limonene [68]. Thus,starting from (S)-hmonene, the biohydrolysis of the mixture of (4S,81 S)-epoxides led to unreacted (4S,8S)-epoxide and (4S,8i )-diol. The former showed a diastereomeric purity (> 95%) and was chemically transformed into (4S,8S)-a-bisabolol. The formed diol... 

The stmctural complexity and biological activity of the cyathane family of diterpenes has stimulated considerable interest from synthetic chemists, as reflected in the number and diversity of approaches reported thus far [42]. Our own strategy for cyathane synthesis is based on a rhodium-catalyzed [5+2] cycloaddition. The precursor for this reaction was fashioned ultimately from commercially available and inexpensive (S)-(-)-limonene. Treatment of the ketone 139 with 5 mol% [RhCl(CO)2]2 in 1,2-dichloro-ethane gave cycloadduct 140 (Scheme 13.14) in 90% yield and in analytically pure form after simple filtration through a plug of neutral alumina [43]. 

The synthesis shown in Scheme 13.7 used limonene as the starting material (R = CH3 in Scheme 13.6) whereas Scheme 13.8 uses the corresponding aldehyde... 

More recently, Bachi and coworkers extended and adapted the TOCO reaction to the synthesis of 2,3-dioxabicyclo[3.3.1]nonane derivatives hke 228 (Scheme 52) ° ° . As detailed in Scheme 53a, the bridged bicyclic hydroperoxide-endoperoxides hke 229 are obtained, from (S )-limonene (227), in a 4-component one-operation free-radical domino reaction in which 5 new bonds are sequentially formed. Particular experimental conditions are required in order to reduce the formation of by-products 230 and (PhS)2, and to favor the critical 6-exo-ring closure of peroxy-radical 231 to carbon-centered radical 232206 chemoselective reduction of bridged bicyclic hydroperoxide-endoperoxides... 

Figure 5.7. There are many examples now known of the synthesis of NPs via matrix pathways (see also Figure 9.3). However, a nice example of the benefit of such flexibility was revealed when a mutant of spearmint that had smelled more like peppermint was studied.A comparison of the terpenes in both plants revealed that the single gene mutation had not resulted in a single chemical change but multiple changes, in the mutant plant, a hydroxyl group was added to the 3-position of the cyclohexene ring of limonene while the wild-type hydroxylated the 6-position. Some of the other wild-type tailoring enzymes in the mutant did not discriminate fully between the 3- and 6-hydroxylated products so a new family of NPs were produced which gave the mutant plant an odour of peppermint.

Besides the synthesis of racemic dehydroiridodiol [37], some ex-chiral-pool syntheses using (S)-limonene have been described [38]. Dehydroiridodial was synthesized in the same manner [39]. Since the increasing number of cyclopentanoid natural products and their interesting biological activity has stimulated considerable interest in the synthesis of such compounds, we have used our methodology to provide a new asymmetric synthesis of dehydroiridodial, dehydroiridodiol, as well as analogues [40]. 

The preferred industrial method of carvone synthesis utilizes the selective addition of nitrosyl chloride to the endocyclic double bond of limonene. If a lower aliphatic alcohol is used as solvent, limonene nitrosochloride is obtained in high yield. It is converted into carvone oxime by elimination of hydrogen chloride in the presence of a weak base. Acid hydrolysis in the presence of a hydroxylamine acceptor, such as acetone, yields carvone [88]. 

The main renewable resource for L-carvone is spearmint oil (Mentha spicata), which contains up to 75% of this flavour chemical. There also exists a synthetic process for the manufacturing of L-carvone, which is based on (-t)-limonene, which is available as a by-product of the citrus juice industry as a major component of orange peel oil (Scheme 13.4). The synthesis was developed in the nineteenth century and starts with the reaction of (-t)-limonene and nitrosyl chloride, which ensures the asymmetry of the ring. Treatment with base of the nitrosyl chloride adduct results in elimination of hydrogen chloride and rearrangement of the nitrosyl function to an oxime. Acid treatment of the oxime finally results in l-carvone. 

Scheme 13.4 Chemical synthesis of l-carvone from (+)-limonene...

Total synthesis of racemic limonene by Diels-Alder reaction of isoprene with methyl vinyl ketone and subsequent Wittig reaction of the resulting ketone with methylene triphenylphosphorane... 

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