3-Pinene reduction

Borneol and isoboineol are respectively the endo and exo forms of the alcohol. Borneol can be prepared by reduction of camphor inactive borneol is also obtained by the acid hydration of pinene or camphene. Borneol has a smell like camphor. The m.p. of the optically active forms is 208-5 C but the racemic form has m.p. 210-5 C. Oxidized to camphor, dehydrated to camphene. 

Another important use of a-pinene is the hydrogenation to i j -pinane (21). One use of the i j -pinane is based on oxidation to cis- and /n j -pinane hydroperoxide and their subsequent catalytic reduction to cis- and /n j -pinanol (22 and 23) in about an 80 20 ratio (53,54). Pyrolysis of the i j -pinanol is an important route to linalool overall the yield of linalool (3) from a-pinene is about 30%. Linalool can be readily isomerized to nerol and geraniol using an ortho vanadate catalyst (55). Because the isomerization is an equiUbrium process, use of borate esters in the process improves the yield of nerol and geraniol to as high as 90% (56). 

Another important process for linalool manufacture is the pyrolysis of i j -pinanol, which is produced from a-pinene. The a-pinene is hydrogenated to (73 -pinane, which is then oxidized to cis- and /n j -pinane hydroperoxide. Catalytic reduction of the hydroperoxides gives cis- and /n j -pinanol, which are then fractionally distilled subsequendy the i j -pinanol is thermally isomerized to linalool. Overall, the yield of linalool from a-pinene is estimated to be about 30%. 

With phosphorus pentachloride it yields myrtenyl chloride, CioHi Cl, which by reduction with sodium and alcohol yields pinene. 

Maikov et al. [37] prepared a series of C2-symmetric bipyridine-type ligands, the chiral moieties arising from the isoprenoid chiral pool (/3-pinene, 3-carene, 2-carene, or a-pinene, for example). Some representative examples are drawn in Scheme 16 (see 25, 26, 27) and were used as copper ligands of a copper(I) species obtained by an in-situ reduction of Cu(OTf )2 with phenyl-hydrazine. The use of the resulting catalysts in enantioselective cyclopropana-tion proceeded with up to 76% ee (for ligand 27) and high diastereoselectivity (up to 99 1). 

New chiral oxazaborolidines that have been prepared from both enantiomers of optically active inexpensive a-pinene have also given quite good results in the asymmetric borane reduction of prochiral ketones.92 Borane and aromatic ketone coordinate to this structurally rigid oxazaborolidine (+)- or (—)-94, forming a six-membered cyclic chair-like transition state (Scheme 6-41). Following the mechanism shown in Scheme 6-37, intramolecular hydride transfer occurs to yield the product with high enantioselectivity. With aliphatic ketones, poor ee is normally obtained (see Table 6-9). 

Several optically active glycols were prepared from (+ )-limonene and (+ )-a- and (- )-(J-pinene by oxidation with KMn04 (74). An extensive study of the reduction of acetophenone by a complex of LAH and (+ )-l-hydroxycarvomen-thol (51) was made varying solvents and temperature, and the effect of added... 

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]. 

Alcohols are oxidized to aldehydes by the liver enzyme alcohol dehydrogenase, and aldehydes to carboxylic acids by aldehyde dehydrogenase. In mammals, monooxygenases can be induced by plant secondary metabolites such as a-pinene, caffeine, or isobornyl acetate. Reduction is less common and plays a role with ketones that cannot be further oxidized. Hydrolysis, the degradation of a compound with addition of water, is also less common than oxidation. 

No reactions have been observed when methylenecyclopentane (182), methylenecyclohexane (183), or A1(7)-p-menthene (184) were submitted to photosensitized oxygenation.187 On the other hand, methylene-cycloheptane (185)1B7, jS-pinene (187)197, A4<10)-carene (190),202 and sabinene (193)205 undergo slow photosensitized oxygenation reactions giving rise to the formation of primary alcohols 186,189,191,192, and 194, respectively, after reduction of the primarily formed... 

Brown, H. C. and Ramachandran, P. V. Asymmetric Reduction with Chiral Organoboranes Based on a-Pinene. Acc. Chem. Res. 1992, 25, 16-24. 

Several additional studies were carried out to obtain information about the precise behavior of the various components in the model system. The interplay between the manganese porphyrin and the rhodium cofactor was found to be crucial for an efficient catalytic performance of the whole assembly and, hence, their properties were studied in detail at different pH values in vesicle bilayers composed of various types of amphiphiles, viz. cationic (DODAC), anionic (DHP), and zwitterionic (DPPC) [30]. At pH values where the reduced rhodium species is expected to be present as Rh only, the rate of the reduction of 13 by formate increased in the series DPPC < DHP < DODAC, which is in line with an expected higher concentration of formate ions at the surface of the cationic vesicles. The reduction rates of 12 incorporated in the vesicle bilayers catalyzed by 13-formate increased in the same order, because formation of the Rh-formate complex is the rate-determining step in this reduction. When the rates of epoxidation of styrene were studied at pH 7, however, the relative rates were found to be reversed DODAC DPPC < DHP. Apparently, for epoxidation to occur, an efficient supply of protons to the vesicle surface is essential, probably for the step in which the Mn -02 complex breaks down into the active epoxidizing Mn =0 species and water. Using a-pinene as the substrate in the DHP-based system, a turnover number of 360 was observed, which is comparable to the turnover numbers observed for cytochrome P450 itself. 

Asymmetric reduction of a,f -acetylenic ketones. This borane can be used to reduce 1-deulerio aldehydes to chiral (S)-l-deulerio primary alcohols in 90% optical yields. It also reduces a,/ -acctylcnic ketones to (R)-propargylic alcohols with enantiomeric purity of 73-100%. The ee value is increased by an increase in the size of the group attached to the carbonyl group. The value is also higher in reductions of terminal ynones. Alcohols of the opposite configuration can be obtained with the reagent prepared from (— )-a-pinene. 

Enantioselective reductions. The neat reagent (1), prepared from ( + )-< -pinene, reduces aryl a-halomethyl ketones slowly but in high chemical yield to (R)-halohydrins in 90-96% ee, but optical induction is mediocre in the case of aliphatic a-halo ketones (35-66% ee). The chiral halohydrins are useful precursors to chiral epoxides. 

Borane ). This reagent is commercially available or prepared by hydroboration of (-)-a-pinene (16) with 9-BBN (17).10 The stereoselectivity of carbonyl group reduction with (S)-Alpine Borane is explained via six-membered transition state 18. 

Electrochemical reduction of the ozonization products from monoterpenes, i.e., />-meth-l-ene, (-l-)-limonene, (+ )-a// /ia-pinene, (+)-car-3-ene, provides the corresponding double-bond cleavage products in 45-70% yields57. The electrolysis of the acetyloxy hydroperoxide 28 derived from p-menth-l-ene 27 is carried out in an Ac0H/H20(6/1 v/v)— AcONa— (Pb/Pb) system at —1.1 to —1.4V vs. SCE, 2.0 to 2.2 A/dm2 in a divided cell to give the corresponding keto-alcohol 29 in 70% yield (Scheme 3-10). 

Chiral addition of allyl metals to imines is one of the useful approaches toward the synthesis of homoallylic amines. These amines can be readily converted to a variety of biologically important molecules such as a-, / -, and y-amino acids. Itsuno and co-workers utilized the allylborane 174 derived from diisopropyl tartrate and cr-pinene for the enantioselective allylboration of imines. The corresponding iV-aluminoimines 173 are readily available from the nitriles via partial reduction using diisobutylaluminium hydride (DIBAL-H) <1999JOM103>. Recently, iV-benzyl-imines 176 have also been utilized for the asymmetric allylboration with allylpinacol boronate 177 in the presence of chiral phosphines as the chiral auxiliaries to obtain homoallylic A -benzylamines 178 in high yield and selectivity (Scheme 29) <2006JA7687>. 

In addition, monoterpenes can provide some useful chiral reagents, such as the pinene-based organoborane reagents for chiral reductions, which have been reviewed extensively.42 Camphor-derived organic acids such as camphenesulfonic acid can be used for the resolution of racemic bases and is a common practice in industry (Chapter 6). 

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