Acyloin condensation
| Acyloin condensation | |
|---|---|
| Reaction type | Coupling reaction |
| Identifiers | |
| Organic Chemistry Portal | acyloin-condensation |
| RSC ontology ID | RXNO:0000085 |
Acyloin condensation is a
The reaction is most successful when R is
The reaction is performed in
Independent of
Acyloin cyclization of diesters
Intramolecular acyloin condensation is a classical approach for aliphatic ring synthesis, and "one of the best ways of closing rings of 10 members or more".[4] 3-membered rings are not accessible through the acyloin condensation, 5- and 6-membered rings form in high yield (80 – 85% yield), 4-, 7-, 10-, and 11-membered rings form in moderate yield (50 – 60% yield),[5] 8- and 9-membered rings form in poor to modest yield (30 – 40% yield), and finally, 12-membered and higher rings form in good to excellent yields (>70% yield).[6] For larger rings, unsaturation does not inhibit cyclization.[4] Although yields for 4-membered and medium-sized rings are poor to moderate, the acyloin condensation constitutes one of the earliest practical cyclization reactions to prepare these challenging ring sizes.
For example, tropolone is prepared via an initial acyloin condensation that delivers 2-hydroxycycloheptanone:[7]
Comparison with other ring syntheses
The Dieckmann method is practical only for 5- to 8-membered rings (with modest yields for 7- and 8-membered). The Thorpe method is more easily modified via high dilution (e.g., 0.001 M in benzene/ether) to enable the synthesis of large rings, but 4-membered and 9- to 13-membered rings are still not accessible. Concentration is much less important a factor for obtaining high yields for the acyloin condensation, as the reaction occurs on the surface of the sodium metal.[8] Although, the need for sodium metal limits the functional group tolerance of the reaction, compared to more modern cyclization reactions (e.g. Yamaguchi esterification, ring-closing olefin metathesis), the acyloin condensation continues to be used in the synthesis of complex natural products for the preparation of challenging ring systems.[9]
Mechanism
The mechanism consists of four steps:
- Oxidative ionization of two sodium atoms on the double bond of two ester molecules.
- Wurtz-type coupling between two molecules of the homolytic ester derivative. Alkoxy-eliminations in both sides occur, producing a 1,2-diketone.
- Oxidative ionization of two sodium atoms on both diketone double bonds. The sodium enediolate is formed.
- tautomerizes to acyloin.[10]
Additives
The reaction also produces stoichiometric quantities of
In general, very pure sodium results in lower yields, as the reaction is dependent on a catalytic
Usually
See also
References
- Compt. Rend.(in French). 140: 1593–1595.
- .
- ^ Bloomfield, J. J.; Owsley, D. C.; Nelke, J. M. Org. React. 1976, 23.
- ^ a b c d Smith (2020), March's Organic Chemistry, 8th ed. Rxn. 19-82.
- .
- ISBN 978-81-7709-605-7.
- .
- OCLC 27813843.
- OCLC 60792519.
- ^ Acyloin condensation
- .
