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10-Camphorsulfonic Acid, also known as CSA, is a white crystalline compound with a molecular formula of C10H16O4S and a molecular weight of 232.30. It has a melting point of 203~206oC and is soluble in dichloromethane, methanol, and benzene, but insoluble in ether.
CSA can be prepared by sulfonation of camphor with acetic anhydride-sulfuric acid and purified through recrystallization with ethyl acetate. It is commercially available from major multinational reagent companies.
It is important to note that CSA is hygroscopic and corrosive.
CSA is widely used as an acid catalyst and chiral auxiliary in organic synthesis.
CSA is commonly used as an acid catalyst in organic synthesis, particularly in the addition of hydroxyl groups to alkenes, aldehydes, and ketones to form ethers or hemiacetals/hemiketals. These reactions are typically carried out in dichloromethane solvent and exhibit excellent stereoselectivity due to the unique structure of CSA. For example, CSA can catalyze the intramolecular stereoselective addition of hydroxyl groups to double bonds (Scheme 1). It is also used for the protection of hydroxyl groups, such as the generation of tetrahydropyran-based ethers using dihydropyran and a catalytic amount of CSA (Scheme 2).
CSA is highly effective as a catalyst for the intramolecular ring-opening reactions of epoxides. The size of the oxygen-containing heterocycle depends on the structure of the hydroxyl epoxide. When there is a saturated carbon chain on the other side of the epoxide at the α position, tetrahydrofuran derivatives are formed (Scheme 5). However, when there is an electron-rich double bond at this position, the reaction proceeds through a different mechanism, stabilizing the nucleophilic substitution intermediate, and leads to tetrahydropyran derivatives (Scheme 6). This method can also be extended to the synthesis of eight-membered rings (Scheme 7).
CSA can also be used for the synthesis of spirocyclic aldehydes, exhibiting good yields and stereoselectivity when the hydroxyl group is appropriately positioned within the molecule (Scheme 8).
Due to its unique spatial structure, CSA and its derivatives often exhibit good stereoselectivity in their reactions. After the reaction, the camphor ring can be easily removed (Scheme 9, Scheme 10). These derivatization reactions include substitution, condensation, and addition reactions.
Camphor-derived oxygen-nitrogen heterocycles are used in the asymmetric oxidation of sulfides and disulfides, leading to sulfoxides and sulfonic esters. They are also employed in the epoxidation of alkenes. For the hydroxylation of esters, amides, and ketones with enolate lithium, camphor-derived oxygen-nitrogen heterocycles are the preferred reagents (Scheme 11).
