Swern oxidation variations

The variation of the Swern oxidation is the Corey-Kim oxidation Treatment of DMS (Me2S) with CI2 or N-chlorosuccinimide (NCS) forms dimethylchlorosulfonium ion (A), which reacts with alcohol to form sulfoxonium complex B. Treatment of sulfoxo-nium complex B with a base Et3N gives the corresponding aldehyde or ketone via ylide C (Scheme 7.8). 

One example is Swern oxidation, which uses oxalyl chloride and DMSO and is particularly suitable for the selective oxidation of alcohols to aldehydes or ketones. The disadvantages of this oxidation method are the need for low temperatures, the smell of the dimethyl sulfide formed and the possible oxidation of other heteroatoms. Dess-Martin periodinane (DMP, 5) or iodoxybenzoic acid (IBX, 6) are also common oxidizing agents. The main advantage of these two methods is the short reaction time at room temperature. However, typical problems are the low solubility of IBX and the formation of byproducts. In this context, Finney et al. have reported an interesting procedure avoiding these problems by a variation of the temperature IBX is sufficiently soluble in solvents such as ethyl acetate or dichloromethane at elevated temperatures, whereas it is insoluble in these solvents at room temperature. Because of this, the remaining IBX as well as the IBX-derived byproducts can be separated from the reaction mixture by simple filtration. These reisolated IBX byproducts can then be reoxidized and reused. 

C.i. Swern Oxidation. The variation that is probably the most common in synthesis was discovered by Swern, who found that DMSO can be activated for the oxidation of alcohols by addition of trifluoroacetic anhydride. 6 The reaction is usually done in dichloromethane at temperatures below -30°C. The initially... 

The synthesis of the linker starts with resin-bound sulfinate 462 that is alkylated firstly with bromobenzylbromide 463 and secondly with propylene oxide 464. Selective monoalkylation has been achieved for both steps and the resulting alcohol 465 was oxidized via Swern oxidation yielding ketone 466. The basic conditions of Swern oxidation are in this case sufficient for elimination and thus a,/3-unsaturated ketones 467 are released from the resin. By slight variation of the aliphatic resin-bound compound, Kurth et al. proved the success of the oxidation/elimination model for the release of cyclic derivatives like cyclopentenones [290]. 

Oxidation of the quinine C-9 hydroxy substituent to the ketone is best accomplished using the Woodward3 benzophenone/potassium t-butoxide method, now using toluene. The other oxidation methods investigated (Swern, Jones, ROCI variations) were less effective or limited because of the poor solubility of the substrate. Thermodynamic equilibration of these ketones has also been reported.3... 

According to the standard protocol (procedure A) as described by Swern et at., the alcohol is allowed to react with activated DMSO for 15 min at low temperature (normally —78 to —50°C). This is followed by the addition of triethylamine, which reacts with the activated alcohol, while the reaction is left to reach room temperature. This standard protocol, involving the generation of activated DMSO in CH2C12 at low temperature (ca. -60°C), followed by activation of the alcohol for 15 min, addition of triethylamine and after 5 min allowing the reaction to heat up slowly to room temperature, is found suitable for most substrates. However, some variations have been introduced to suit the oxidation of diverse alcohols. 

Another variation on the Swern-Moffat oxidation, using the... 

There are several variations of the Swern protocol, where the oxalyl chloride is replaced by another activator. Acetic anhydride or trifluoroacetic anhydride is sometimes used. Carbodiimides (R-N=C=N-R) are yet another alternative—the reaction in that case is called a Pfltzner-Mojfatt oxidation. 

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