Acyloin

Synthesis

Classic organic reactions exist for the synthesis of acyloins.

• The acyloin condensation is a reductive coupling of esters, and particularly effective for macrocycle synthesis. Similarly, in rare cases, pinacol conditions couple an aldehyde or ketone and a lactone to give an acyloin.
• The benzoin condensation is condensation reaction between aldehydes catalyzed by carbene-like nucleophiles
• Oxidation of carbonyls is possible with molecular oxygen but not selective
• Better alternative is oxidation of corresponding silyl enol ethers with mCPBA in the Rubottom oxidation
• MoOPH oxidation of carbonyls is a system with molybdenum peroxide, pyridine and hexamethylphosphoramide.
• A family of stereoselective syntheses oxidizes in situ enols with nitroso equivalents. In the simplest version, nitrosobenzene oxidizes a carbonyl to an α‑hydroxylamine, with a proline organocatalyst for enantioselection. In a more elaborate version, enolates can be oxidized by sulfonyloxaziridines.

Oxidation with Sulfonyloxaridines

When sulfonyloxaziridines oxidize enol(ate)s, the latter reacts by nucleophilic displacement at the electron deficient oxygen of the oxaziridine ring.

This reaction type is extended to asymmetric synthesis by the use of chiral oxaziridines derived from camphor (camphorsulfonyl oxaziridine). Each isomer gives exclusive access to one of the two possible enantiomers. This modification is applied in the Holton taxol total synthesis.

In the enolate oxidation of the cyclopentadienone below with either camphor enantiomer, the trans isomer is obtained because access for the hydroxyl group in the cis position is limited. The use of the standard oxaziridine did not result in an acyloin.