Camphors, Wagner-Meerwein rearrangement

Bomeol is oxidized to camphor with chromic or nitric acid dehydration with dilute acids yields camphene. Bomeol is readily esterified with acids, but on an industrial scale bornyl esters are prepared by other routes. For example, levorotatory bomeol is synthesized industrially from levorotatory pinenes by Wagner Meerwein rearrangement with dilute acid, followed by hydrolysis of the resulting esters [86]. 

Camphor is of considerable importance technically, being used in the manufacture of celluloid and medicinal products. It is manufactured industrially from a-pinene, obtained from turpentine, by several processes (66-107) which differ mainly in detail. Synthetic camphor is usually obtained as the racemic modification. The formation of camphor involves the Wagner-Meerwein rearrangements, e.g. ... 

The C-8-substituted derivatives of camphor are formed by a route from 3,3-dibromocamphor (33) outlined in Scheme 1This involves a series of Wagner-Meerwein rearrangements. 

These variously substituted camphor derivatives have in turn been used in a number of syntheses of natural products, some of which also involve Wagner-Meerwein rearrangements in their later stages. Examples drawn from the syntheses of (+)-a-santalene (34),(-)-3-santalene (35), (-)-copacamphene (36) and (-)-sativene (37) are given in Schemes 12-14. 

For an excellent formal treatment of the Wagner-Meerwein rearrangements of camphor in sulfuric acid, which makes extensive use of l4C labeling, see 0. R, Rodig and R. J. Sysko, J. Am, Chem. Soc.,94, 6475 (1972). 

Wagner-Meerwein rearrangements occur extremely frequently among branched-chain aliphatic and alkylaryl compounds, and are particularly important in the terpene and camphor series. An example of rearrangement of type a) is that of camphene hydrochloride (1) into isobornyl chloride (2), for which Meerwein and van Emster141 give the following directions ... 

Similarly, the bornyl carbocation (2.17) can react with water to give borneol and this can be oxidised to camphor, the characteristic odorant of camphor wood. The isocamphane skeleton is formed by a Wagner-Meerwein rearrangement of the bornyl carbocation. 

Camphor had been prepared from camphoric acid by Haller. Komppa synthesised camphoric acid from dimethylglutaric ester and from it obtained camphor. Perkin and J. F. Thorpe independently synthesised camphoric acid. When Komppa (1909) published the details of his synthesis, Thorpe and G. L. Blanc doubted its validity, but later confirmed that Komppa was correct. The formation of camphene from bornyl chloride involves what is called a Wagner-Meerwein rearrangement. ... 

The Martinez group has demonstrated the versatility of the Wagner-Meerwein rearrangement in the enantiospecific synthesis of C(10)-substituted camphors and fenchones from readily available (-i-)-camphor (103) and (-)-fenchone (104). These derivatives represent a multitude of substitution tjmes, including C(10)-O-, C(10)-Br-, C(10)-S-, C(10)-Se-C(10)-N-, C(10)-C-N-, and C(9,10)-dihalocamphors. They are of... 

As demonstrated below, the general procedure begins by treatment of camphor with triflic anhydride and a non-nucleophilc base to give allyl triflate 107 via Wagner-Meerwein rearrangement of 105 followed by elimination. Reduction of 107 with LiAULj then results in allylic alcohol... 

Figure 3.11 shows the biosynthesis of (+)-bornyl pyrophosphate (the precursor of (-l-)-borneol (28) and (+)-camphor (29)) and of (+)-sabinene (30) (the precursor of the thujones) from 3R)-20 cyclized in an anti,endo conformation (Wise et al. 1998). Other related products include camphene (31) and 1,8-cineole (32). The chemistry involved in the formation of the final products includes Wagner-Meerwein rearrangements of hydride and (in the case of camphene) a skeletal carbon-carbon bond as well as simple cyclizations. The biosynthesis of (-)-a-and P-pinene (33 and 34) proceeds along similar lines from (3S)-20 and is shown in Figure 3.12. 

The most recent sulfide catalyst (13) made from D-camphor was reported by Huang and coworkers in 2008, which was obtained via an unexpected Wagner-Meerwein rearrangement of a dimesylate intermediate [20]. Various aromatic aldehydes can be converted into the corresponding trans 1,2-diaryl oxiranes in excellent diastereoselectivities (90 to >99% de) and high enantioselec-tivities (86-96% ee). Notably, this sulfide catalyst is also efficient for aliphatic aldehydes moderate yields (51-57%) and good enantioselectivities (71-85% ee) were observed with cyclohexane carboxaldehyde, valeraldehyde, and isovaleralde-hyde (Table 20.1). Notably, the asymmetric induction was reversed in the case of... 

Functionalization at C-9 (see Scheme 10) in camphor illustrates not only the complexity of the pathways when the possibility of Nametkin (2,3-methyl shift) and 2,6-hydride shifts are taken into account, but also one of the solutions to the simplification of the rearrangement.The product is a mixture of (-) )-and (-)-camphor-9-sulfonic acids, i.e. the pathway allows for racemization. Indeed camphor itself can be racemized in concentrated sulfuric acid by a similar pathway involving both Wagner-Meerwein and... 

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