Swern Oxidation

Описание: The Swern Oxidation allows the preparation of aldehydes and ketones from primary and secondary alcohols. The oxidation of alcohols by DMSO and TFAA or oxalyl chloride.

General features:
1. DMSO reacts vigorously with oxalyl chloride when no solvent is present. It can lead to an explosion. The most common solvent is DCM.
2. The oxidation is usually conducted at -78 ºC to stabilize the intermediates of the reaction.

Procedure:
Reaction of DMSO with oxalyl chloride at low temperature followed by the slow addition of the alcohol. Then, the tertiary amine is added to facilitate the decomposition of the alkoxysulfonium salt leading to the desired product.

Reaction mechanism:
1. Activation of DMSO with oxalyl chloride, (COCl)2.
2. Formation of the chlorosulfonium salt.
3. Activation of the alcohol and formation of an alkoxysulfonium salt.
4. Deprotonation and formation of an alkoxysulfonium ylide.
5. The sulfur ylide decomposes to give the carbonyl compound and DMS.

Pinterest:
https://www.pinterest.es/pin/67166973...
https://www.pinterest.es/pin/67166973...

Experimental procedure:
To a solution of oxalyl chloride (4.57 g, 36.0 mmol, 1.50 eq.) in DCM (36 mL) was added a solution of dimethylsulfoxide (4.60 mL, 64.8 mmol, 2.70 eq.) in DCM (15 mL) at -78 °C over 5 min. After 5 min, a solution of the secondary alcohol (24.0 mmol, 1.00 eq.) in DCM (24 mL) was added dropwise over 5 min. After 30 min at -78 °C, triethylamine (23.4 mL, 168 mmol, 7.00 eq.) was added dropwise over 10 min. The mixture was allowed to warm-up to room temperature, and water (150 mL) was added. The product was extracted with DCM (3 x 150 mL). The combined organic layers were washed with brine, dried over sodium sulfate, and concentrated. Purification by FCC (4:1 → 2:1 PE:EtOAc) afforded the corresponding ketone (20.2 mmol, 84 % yield).
Adapted from Angew. Chem. Int. Ed. 2020, 59, 13990. https://doi.org/10.1002/anie.202005380

The authors:
D. Swern and co-workers reported in 1976 that the treatment of dimethyl sulfoxide with trifluoroacetic anhydride below -50 ºC in dimethyl chloride gave an intermediate compound that reacted rapidly with primary and secondary alcohols.

References:
https://nrochemistry.com/swern-oxidat...

Seminal publications:
1. J. Org. Chem. 1976, 41, 957-962. https://doi.org/10.1021/jo00868a012
2. doi:10.1016/0040-4020(78)80197-5. https://doi.org/10.1016/0040-4020(78)...

Similar reactions:
Parikh-Doering oxidation:    • Parikh-Doering Oxidation  
Ley-Griffith oxidation:    • Ley-Griffith Oxidation  
Baeyer-Villiger oxidation:    • Baeyer-Villiger Oxidation  
Corey-Kim oxidation:    • Corey-Kim Oxidation  
Corey-Gilman-Ganem oxidation:    • Corey-Gilman-Ganem Oxidation