Camphorsulfonic-acid

Solubility sol dichloromethane, methanol, benzene insol ether. Form Supplied in white crystals, racemic ( ). 

Preparative Methods commercially available from several sources can be prepared by sulfonation of camphor with acetic-sulfuric anhydride.  

Acid Catalyst. Camphorsulfonic acid (CS A) has been used extensively in synthetic organic chemistry as an acid catalyst. It has particularly been used in protecting group chemistry. For example, hydroxyl groups can be protected as tetrahydropyranyl (THP) ethers using dihydropyran and a catalytic amount of CSA (eq 1). Both 1,2- and 1,3-diols can be selectively protected by reaction with orthoesters in the presence of camphorsulfonic acid to form the corresponding cyclic orthoester (eq 2) This method of protection is particularly useful in that reduction of the orthoester with Diisobutylaluminum Hydride forms the monoacetal, which allows for preferential protection of a secondary alcohol in the presence of a primary alcohol. Ketones have also been protected using catalytic CSA (eq 3).  

A list of General Abbreviations appears on the front Endpapers 

Overman has shown that camphorsulfonic acid can also be used in nucleophile-promoted alkyne-iminium cyclizations. Alky-lamines can react with formaldehyde and sodium iodide to yield piperidines in good yield. This methodology has been applied in the total synthesis of pumiliotoxin A (eq 4).  

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The spontaneous polymerization of styrene was studied in the presence of various acid catalysts (123) to see if the postulated reactive intermediate DH could be intentionally aromatized to form inactive DA. The results showed that the rate of polymerization of styrene is significantly retarded by acids, eg, camphorsulfonic acid, accompanied by increases in the formation of DA. This finding gave further confirmation of the intermediacy of DH because acids would have Httie effect on the cyclobutane dimer intermediate in the Flory mechanism. 

This amide is readily prepared from the acid chloride (Pyr, rt, 1 h, 77-86% yield) or the acid (DCC, DMAP, CH2CI2, rt, 1 h, 88% yield). Treatment of the amide with camphorsulfonic acid forms an A-acylindole. The acid can be regenerated from the A-acylindole by Li0H/H202/THF/H20 or NaOH/MeOH. Alternatively, it can be transesterified with MeOH/TEA, converted to an amide, by heating with an amine or converted to an aldehyde by DIB AH (62-85% yield). ... 

A -sulfinyl chiral auxiliaries have been used to prepare enantiopure tetrahydro-P-carbolines and tetrahydroisoquinolines in good yields under mild reaction conditions. Both enantiomers of V-p-toluenesulfinyltryptamine 46 could be readily prepared from the commercially available Andersen reagents.Compound 46 reacted with various aliphatic aldehydes in the presence of camphorsulfonic acid at -78 °C to give the A-sulfinyl tetrahydro-P-carbolines 47 in good yields. The major diastereomers were obtained after a single crystallization. Removal of the sulfinyl auxiliaries under mildly acidic conditions produced the tetrahydro-P-carbolines 48 as single enantiomers. 

DL-2-Thio-1 -phenyl-imidazolidine 1,2-Dibromoethane d-10-Camphorsulfonic acid... 

Calcium carbonate as support for palladium catalyst, 46, 90 Calcium hydride, 46, 58 D,L-Camphor, sulfonation to d,l-10-camphorsulfonic acid, 46,12 10-Camphorchlorosulfoxide, 46, 56 d,l-10-Camphorsulfonic acid, 46,12 conversion to acid chloride, 45,14 10-Camphorsulfonyl chloride, 45, 56 d,l-10-Camphorsulfonyl chloride,... 

The synthesis of the right-wing sector, compound 4, commences with the prochiral diol 26 (see Scheme 4). The latter substance is known and can be conveniently prepared in two steps from diethyl malonate via C-allylation, followed by reduction of the two ethoxy-carbonyl functions. Exposure of 26 to benzaldehyde and a catalytic amount of camphorsulfonic acid (CSA) under dehydrating conditions accomplishes the simultaneous protection of both hydroxyl groups in the form of a benzylidene acetal (see intermediate 32, Scheme 4). Interestingly, when benzylidene acetal 32 is treated with lithium aluminum hydride and aluminum trichloride (1 4) in ether at 25 °C, a Lewis acid induced reduction takes place to give... 

The completion of the synthesis of key intermediate 2 requires only a straightforward sequence of functional group manipulations. In the presence of acetone, cupric sulfate, and camphorsulfonic acid (CSA), the lactol and secondary hydroxyl groups in 10 are simultaneously protected as an acetonide (see intermediate 9). The overall yield of 9 is 55 % from 13. Cleavage of the benzyl ether in 9 with lithium metal in liquid ammonia furnishes a diol (98% yield) which is subsequently converted to selenide 20 according to Grie-co s procedure22 (see Scheme 6a). Oxidation of the selenium atom... 

Contained within intermediate 25 is an acid-labile mixed acetal group and it was found that treatment of 25 with camphorsulfonic acid (CSA) results in the formation of dioxabicyclo[3.3.0]octane 26 in 77 % yield. Acid-induced cleavage of the mixed cyclic acetal function in 25, with loss of acetone, followed by intramolecular interception of the resultant oxonium ion by the secondary hydroxyl group appended to C leads to the observed product. Intermediate 26 clearly has much in common with the ultimate target molecule. Indeed, the constitution and relative stereochemistry of the dioxabicyclo[3.3.0]octane framework in 26 are identical to the corresponding portion of asteltoxin. 

When a solution of 25 in a 1 1 mixture of methanol and methylene chloride is exposed to periodic acid, the dithiane group is cleaved oxidatively to give, after treatment of the crude product with camphorsulfonic acid (CSA) in methanol, bisacetal 12 as a 2 1 mixture of C-12 anomers in a yield of 80% (Scheme 3). Although the conversion of 12 into 10 could be carried out on the mixture of anomers, it was found to be more convenient to carry each isomer forward separately. When 12 is treated with lithium diethylamide, the methine hydrogen adjacent to the lactone carbonyl is removed as a proton to give an enolate which is then oxidized in a completely diastereoselective fashion with Davis s oxaziridine18 to afford 11. 

The hydroxylation reaction, whose stereochemical course is controlled by the strong inherent preference for the formation of a cis-fused 5,5 ring system, creates a molecule which would appear to be well suited for an intramolecular etherification reaction to give ring E of ginkgolide B (1). Indeed, when a solution of 11 in methylene chloride is exposed to camphorsulfonic acid (CSA), a smooth cycli-zation reaction takes place to give intermediate 10 in an overall yield of 75% from 12. The action of CSA on 11 produces a transient oxonium ion at C-12 which is intercepted intramolecularly by the proximal hydroxyl group at C 4. 

Using oxathiane 11, ( + )-(i )-2-methoxy-2-phenylpropanoic acid was obtained in 97% ee, however, the synthesis contains some inconvenient reaction steps. Thus, reduction of ( + )-10-camphorsulfonic acid (8) leads in low yield to a mixture of 10-mercaptoisoborneol (9 A) and 10-mercaptoborneol (9B) which must be separated by chromatography. The oxathiane 10 resists deprotonation with butyllithium and, therefore,, y -butyllithium had to be employed. Furthermore, after addition of methylmagnesium iodide, cleavage of the oxathiane moiety 12, with iodomethane did not proceed as well as with the simpler oxathianes 3. 

Sulfoxides were first prepared in optically active form in 1926 by the classical technique of diastereomeric salt formation followed by separation of the diastereomers by recrystallization16 17. Sulfoxides 1 and 2 were treated with d-camphorsulfonic acid and brucine, respectively, to form the diastereomeric salts. These salts were separated by crystallization after which the sulfoxides were regenerated from the diastereomers by treatment with acid or base, as appropriate. Since then numerous sulfoxides, especially those bearing carboxyl groups, have been resolved using this general technique. 

An interesting phenomenon has been observed in the high pressure Diels-Alder reactions of the l-oxa[4.4.4]propella-5,7-diene (117) with 1,4-naphthoquinone, maleic anhydride and N-phenylmaleimide, where the diene 117 undergoes a rearrangement to the diene isomer 118 which, although thermodynamically less favored, exhibits a greater reactivity [40]. The reactivities of the three dienophiles differed since maleic anhydride and N-phenylmaleimide reacted only in the presence of diisopropylethylamine (DIEA) and camphorsulfonic acid (CSA), respectively (Scheme 5.15). The distribution of the adduct pairs shows that the oxygen atom does not exert a consistent oriental dominance on TT-facial selectivity. 

LP-DE also promotes and accelerates intramolecular Diels-Alder reactions of low reactive polyenones. The use of a catalytic amount of camphorsulfonic acid (CSA) further accelerates the cycloaddition and enhances the diastereo-selectivity [41]. Table 6.7 illustrates the effect of CSA on the intramolecular Diels-Alder reaction of 2-methyl-l,7,9-decatrien-3-one. 

Fig. 14 Microwave-assisted synthesis of pyrazoles and isoxazoles on cellulose. Reagents and conditions a Camphorsulfonic acid, DMF, MW 80 °C, 15 min, open vessel b NH2XH, MW 82 °C, 15 min, open vessel. X = N,0 Y = NH, NEt, O R = Me, i-Pr, BUCH2, PhCH2, Et(Ph)CH, R = alkyl, aUyl, and aryl groups...

Cyclooctatrienyl Cyclopentadienyl Camphorsulfonic acid Cetyltrimethylammonium bromide... 

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