Fluorous DMSO

An unavoidable by-product of the Swem reaction is the volatile dimethylsulphide which, on account of its unpleasant smell, is a reagent regulated by offensive odour control laws. This makes large scale chemistry problematic, especially in industry. To overcome this, several methods exist to perform the Swem oxidation under odourless conditions. For example, Node et al. outline a protocol for the Swem oxidation which uses dodecyl methyl sulfoxide in place of methyl sulfoxide,12 while Crich and co-workers have developed a fluorous Swem oxidation reaction that uses tridecafluorooctylmethyl sulfoxide 17,l3a,b This reagent can be recovered via a continuous fluorous extraction procedure and recycled by reoxidation with hydrogen peroxide. Additionally, the fluorous DMSO is crystalline, odourless and soluble in CH2CI2 to —45 °C. 

Fig. 32 Fluorous mixture synthesis of fused-tricyclic hydantoins. Reagents and conditions a Mo(CO)6, DMSO, toluene, MW 150 °C, 35 min, closed system b TFA CH2CI2 (1 1), rt c PhC2H4NH2, PyBOP, i-Pr2EtN, MeOH, CH2CI2 followed by flash chromatography and F-HPLC d i-Pr2EtN, MeOH, MW 140 °C, 40 min, followed by F-SPE...

A fluorous analogue of DMSO has been used to perform Swern reactions [24], This widely used method of oxidizing an alcohol to an aldehyde falls down seriously from the environmental point of view due to its production of a stoichiometric amount of dimethyl sulfide. Here, a fluorous sulfoxide is prepared and used in the oxidation of several alcohols in dichloromethane, as shown in Scheme 9.12. After reaction, the sulfide is extracted into perfluorohexane and the system recycled. Unfortunately, extraction from dichloromethane was found to be difficult, but replacing the dichloromethane with toluene leads to a more efficient recovery. 

In the same way, the fluorous proline-derivative 7 (see Scheme 5.4) was applied as a catalyst (30mol%) in the intermolecular aldol reaction between acetone and p-nitrobenzaldehyde in BTF as a solvent. The chemical yield (72%) and enantioselectivity (73% ee) were fuUy comparable to those obtained with proline in dimethyl sulfoxide (DMSO), but attempts to recover and reuse the fluorous catalyst failed [35]. 

First, the corresponding sulfide 2 has relatively low volatility and is not malodorous. Second, fluorous sulfide 2 can be easily separated from the reaction mixture by continuous fluorous/organic liquid-liquid extraction and then oxidized to 1 with hydrogen peroxide for reuse. In addition, sulfoxide 1 has similar reactivities and compatibility as DMSO with a variety of functional groups due to the relatively inert nature of the fluorous subunit. 

Introduction. The combination of DMSO, oxalyl chloride, and trlethylamlne (TEA) (Swem oxidation ) has been widely used for the oxidation of primary alcohols to aldehydes and secondary alcohols to ketones due to the mild reaction conditions and the tolerance of a broad range of functional groups (eq 1). However, the malodorous dlmethylsulfide (DMS) derived from DMSO makes the Swem oxidation unpleasant to conduct, especially on a large scale. Reagent 1 is designed as an alternative to DMSO by attaching a fluorous alkyl chain to one of the methyl groups. The introduction of the fluorous portion has two important consequences. 

Experimental Protocol. The experimental protocol for using fluorous sulfoxide 1 in the Swern oxidation is similar to the original one where DMSO is used except for the work-up details. The reactions are typically run in anhydrous CH2CI2 at —30°C for 1-2 h and then warmed to room temperature for 1 h. The reaction mixture is diluted with H2O, washed with saturated NH4CI solution, and then extracted with CH2 CI2. CH2 CI2 is subsequently... 

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