Camphanes

When distilled with phosphorus pentoxide, camphor yields cymene, and with iodine, carvacrol. Both of these bodies are para-derivatives of benzene. On oxidation with nitric acid camphor yields many acids, of which the chief are camphoric acid, CjgHjgO, camphanic acid, CjoHj O, and camphoronic acid, CgHj Og. The constitution of these acids has an important bearing on that of camphor. Many formulae have been suggested for camphor during the past few years, but that of Bredt is now universally accepted, and has received complete confirmation by Komppa s synthesis of camphoric acid. This synthesis confirms the formula for camphoric acid as—... 

Whereas treatment of ( )-29 with camphanic chloride achieves the selective esterification of the hindered C-9 hydroxyl group, the action of acetic anhydride on (+)- 29 results in the equally selective acetylation of the C-10 hydroxyl group It is not clear to what this discrepancy should be attributed, so we will not offer a rationalization here. This unexpected result is, however, most gratifying because TPAP-NMO oxidation27 of the remaining C-9 hydroxyl furnishes keto acetate 6 (88 % overall yield). You will note that the contiguous keto and acetate functions in 6 are both expressed in the natural product. 

The target compound was obtained as a racemic mixture. Enantiomeric pure Efavirenz had to be isolated via a classical chiral resolution of a diastereo-mixture of (-) camphanate imide. 

Alternatively, a second crop of material can be obtained from the aqueous filtrate after several hours. However, a considerable amount of camphanic acid still remains in the aqueous layer thus chloroform extraction of the aqueous phase as described is recommended. To avoid undue exposure to the chloroform vapor, these extractions should be performed in a fume hood. 

Because both enantiomers, (+) and (-)-camphoric add, are available by oxidation either from natural (+)-D-camphor or from natural (-)-L-borneol, both enantiomers of camphanoyl chloride can be prepared conveniently.3 5 The corresponding enantiomers of camphanic acid were described for the first time by Wreden6and Aschan.7 The three-step procedure, described above is an adaptation of procedures described by Aschan,8 Zelinsky et al.,9 Meyer et al.,10 and Gerlach.3... 

The preparation of enantiomerically pure chemicals is also the theme of the next group of four procedures. The biopolymer polyhydroxybutyric acid, which is now produced on an industrial scale, serves as the starting material for the large scale synthesis of (R)-3-HYDROXYBUTANOIC ACID and (R)-METHYL 3-HYDROXYBUTANOATE. Esters of (-)-camphanic acid are useful derivatives for resolving and determining the enantiomeric purity of primary and secondary alcohols. An optimized preparation of (-)-(1S,4R)-CAMPHANOYL CHLORIDE is provided. The preparation of enantiomerically pure a-hydroxyketones from ethyl lactate is illustrated in the synthesis of (3HS)-[(tert)-BUTYL-DIPHENYLSILYL)OXY]-2-BUTANONE. One use of this chiral a-hydroxyketone is provided in the synthesis of (2S,3S)-3-ACETYL-8-... 

As this synthesis started from an achiral starting material, compound 199 must be resolved to secure enantiomerically pure intermediates for the synthesis of taxol. Treatment of (+ )-diol 199 with excess ( lA)-( )-camphanic chloride in methylene chloride in the presence of Et3N forms two diastereomeric monoesters for chromatographic separation. Enantiomerically pure diol 199 can be regenerated from the ester in 90% yield with a specific rotation of +187 (c = 0.5, CHC13). 

Bidentate chiral auxiliaries have since been examined. While camphane-2,3-diol and (5-binaphthol gave disappointing results, tartrate-derived (TADDOL) ligands were found to be very promising as chiral inductors [44]. Particularly interesting results were obtained by using complex 21, readily available from natural (P,J )-(+)-tartaric acid (Scheme 13.21). 

Photolysis of the blue solid (+)-10-bromo-2-chloro-2-nitrosocamphane (270) with red light produces two nitroxide radicals 271 and 272 and 10-bromo camphor 273, 10-bromo-2-chloro-2-nitro camphane 274 in addition to some minor products (equation 122). A complex reaction mechanism has been proposed144. 

As we shall see, optically pure 7-oxanorbom-5-en-2-yl derivatives 31 and 32 can be obtained readily. Saponification of acetate 31 or camphanate 32 gives (lR)-7-oxanorbom-5-en-2-one ((+)-7). In the latter reaction (32 (+)-7) the chiral... 

In the presence of a catalytical amount of Znl2, (-)-l-cyanovinyl camphanate, derived from the commercially available (-)-(lS)-camphanoyl chloride and 2-oxopropionitrile, added to furan (an inexpensive starting material derived from the biomass ) and afforded a 45 45 5 5 mixture of adducts 32/40/41/42 in 90 % yield from which 32 could be isolated (98 % d.e.) in 29 % yield after repetitive... 

Silyl enol ether 139 has also been transformed into D-allose, as shown in Scheme 5. The same methods can be applied to the enantiomeric enol ether derived from camphanate 38, and this allows one to prepare L-allose and its derivatives. Oxidation of 139 with MCPBA in THF (20 °C) led to the product of epoxide acidolysis 147 (69 %) which yielded 148 on heating to 200 °C for 15 min. Addition of 1.1 equiv. of MCPBA converted 148 into lactone 149 which in the presence of MeOH and K2CO3 (20 °C), gave selectively diester 150. Reactions 147... 

Raag, R. and Poulos, T. L. (1991) Crystal structures of cytochrome complexed with camphane, thiocamphor and adamantane factors controlling P450 substrate hydroxylation. Biochemistry 30, 2674-2684. 

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