9-Bromocamphor derivatives

An unusual cyclopropanation of 9-bromocamphor derivatives (5) to a 7-spirocyclo-propyl camphor derivative (6) has been realized by the action of potassium r-butoxide (or sodium hydride) in warm DMSO (Scheme 8).29 The exo-hydroxy group and a nonhydrogen endo-substituent at C(2) were proven to be essential structural elements, and the solvent DMSO the sole effective reaction medium. 

The action of magnesium on a-halo ketone has been used by Malmgren, for the synthesis of bromomagnesium enolate 2 derived from 3-bromocamphor 1 (equation 1) . 

Chemical Resolution of Compounds Containing Basic Groups. 3-Bromocamphor-8-sulfonic acid has been widely used as a resolving agent for compounds containing basic groups. A number of primary (1), secondary (2), and tertiary (3) amines as well as oxazolines (4) have been resolved by the formation of diastereomeric salts derived from 3-bromo-8-camphorsulfonic acid. 

The ring-opening oxidation with nitric acid of 3,7i-dibromocamphor (246) has been re-examined by Brienne and Jacques, who have shown that treatment of the r-bromocamphoric acid (247 R = H) thus obtained with one equivalent of alkali gives the unusual trans-fused y-lactone [(248 R = H), the trans-n-cam-phanic acid of the 19th century]. The structure already derives from the fact that... 

Bromocamphor has been employed as the chiral starting material in an enantiospecific synthesis (ref. 146) which involved the formation of an indanone (CD moiety) related structurally to that used by Hoffmann-La Roche and led finally to (-)-estrone. Attempts to alkylate the a,p-unsaturated ketone with 2-(3-methoxyphenyl)ethyl iodide failed, not surprisingly, due to an elimination rather than the desired substitution reaction and accordingly the use of an a-methylenic derivative of the ketone and 3-methoxybenzyl chloride were obligatory. By the use of (-)-3-bromocamphor, which is readily available from (-)-borneol by oxidation to (-)-camphor and bromination, natural (+)-estrone could be obtained. 

Several syntheses of chiral camphor derivatives make use of the CH acidity of the methylene group attached in a-position to the carbonyl function (C-3). Thus, isoamyl nitrite converts camphor to 3-isonitrosocamphor which readily undergoes hydrolysis to the yellow camphorquinone. Bromination leads to 3-bromocamphor which is sulfonated to 3-bromocamphor-3-sulfonic acid with concentrated sulfuric acid. 3-Lithiated camphor obtained with phenyllithium is carboxylated to endo- and exo-isomers of camphor carboxylic acid. The Claisen condensation of camphor with esters of carboxylic acids provides enolized chiral 1,3-diketones, converting metal cations to chiral metal chelates. 

Of the reported analyses of bicyclo[2,2,l]heptane derivatives, that of the (—)-W-ethyl-N-methylalanine oxide (69) salt of (-(-)-3-bromocamphor-sulphonate (70) is of some crystallographic interest since the known... 

Among several terpene derived chiral ketones examined, 3-d-bromocamphor was found to be most satisfactory and 3d-bromocamphor is responsible for the generation of (S)-catalyst. Combination of the racemic catalyst and chiral ketone in a 1 1 ratio gave a better results, suggesting that decomplexation of one enantiomeric organoaluminum reagent and the chiral ketone is more readily facilitated by the addition of aldehyde, thereby allowing the enantioselective activation of the aldehyde for the asymmetric hetero-Diels-Alder reaction. 

Treatment of 3,3-dibromocamphor with bromine and chlorsulphonic acid (conditions under with 3,3,8-tribromocamphor is formed), followed by working-up the crude reaction mixture with zinc and hydrobromic acid to effect selective debromination, provided 8-bromocamphor (456) in a regiospecificprocess. Prolonged treatment of c(,/-camphor with excess BF3, OEt2 and ethyl diazoacetate in ether afforded a 2 1 mixture (63 % yield) of the camphene derivatives (457) and (458). Reaction of the mixture with zinc dust and glacial acetic acid at reflux gave (457) in essentially quantitative yield from (458). ... 

Interestingly, the same research group also found that a mixture of Lewis acid derived from racemic (23a) and Imol equivalent of (+)-3-bromocamphor (149) efficiently catalyzed hetero Diels-Alder reaction of benzaldehyde to give ds-pyrone in 82% ee. This finding was explained by selective complexation to one of the enantiomers of Lewis acid by ketone (149). 

Davis has described many examples of asymmetric epoxidation mediated by oxaziridines. The first chiral oxaziildine reported was derived from bromocamphor 17, but the observed enautioselectivities were low, the best being 40% ee for 1-phenylcyclohexene oxide (Scheme 1.21) [54]. 

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