Sulfoxides fluorous

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. 

Oxidation reactions are not limited to those that occur at a carbon centre. The perfluorinated Ni(F-acac)2-benzene-CgFi7Br system described above was also active for the oxidation of sulfides to sulfoxides and sulfones [28], A sacrificial aldehyde is required as co-reductant, but the reaction may be tuned by changing the quantity of this aldehyde. If 1.6 equivalents of aldehyde are used, the sulfoxide is obtained, whereas higher quantities (5 equivalents) lead to sulfones. Fluorous-soluble transition metal porphyrin complexes also catalyse the oxidation of sulfides in the presence of oxygen and 2,2-dimethylpropanal [29],... 

The vinylogous Pummerer reaction of an amido-substituted sulfoxide produces the tetrahydroisoquinoline (Equation 62) <1995JOC7082>. Benzoyltetrahydroisoquinolinones have also been synthesized under Pummerer-type conditions on polymer support <2005H(65)1881>. Additional later examples highlighted the same reaction incorporating a fluorous-phase cyclative-capture method <2005AGE452>. 

Crich, D., Neelamkavil, S. Improved method of oxidizing primary and secondary alcohols by Swern or Corey-Kim oxidation using a recyclable fluorous sulfoxide as the oxidizing agent. WO 2002-US19274 2003002526, 2003 (The Board of Trustees of the University of Illinois, USA). 

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]. 

Fluorous-tagged reagents are very attractive for reactions in which a stoichiometric by-product is formed that is difficult to separate. An example is perfluor-oalkylated triphenylphosphane for use in Wittig and aza-Wittig reactions, where the corresponding phosphane oxide is removed by fluorous extraction [22, 23]. Similarly, fluorous sulfoxide has been employed in Swern oxidations, and fluorous carbodiimide has been used as a coupling reagent [24, 25]. 

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. 

Hydroxyl protection. Enol ether 1 has been developed. A tetrahydropyranyl sulfoxide 2 is available for the formation of mixed acetals upon activation with Cp2ZrCl2-AgC104. The fluorous bromosilane 3 form siloxanes with improved acid stabilityA method for selective tosylation of diol systems that is known to be catalyzed by organotin oxides is also modifiable in terms of fluorinated catalysts. ... 

Both complexes were able to catalyze the oxidation of jt-substituted methyl phenyl sulfides at a substrate/catalyst molar ratio of 100, with good sulfoxide selectivities (> 90%). It should be noted that FB reactions catalyzed by Mn-14 consistently afforded higher sulfoxide yields than homogeneous reactions catalyzed by Mn-13 (Table 4). Moreover, three consecutive recyclings of the fluorous layer were performed with no appreciable loss of catalytic activity and selectivity. 

The Ni(II) complex of the perfluorinated )8-diketone, C7F15COCHCOC7F15 actively catalyzed the oxidation of a variety of aldehydes to the corresponding carboxylic acids (248) with high jdeld vmder mild conditions (Scheme 49). The solvent used was made of perfluorodecalin and toluene, and the catalyst was recycled several times in the fluorous phase vsrith only a negligible loss of activity. The same catalyst/solvent system was also used for the oxidation of sulfides to sulfones and sulfoxides (Scheme 49). Addition of 2-methylpropanal to this reaction system led to the in situ generation of a peracid, which resulted in high product yields. 

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. 

Applications. Twelve examples are given in ref 2 to demonstrate the applications of fluorous sulfoxide 1 for the oxidation of primary alcohols to aldehydes (eq 2), secondary alcohols to ketones (eq 3), and lactols to lactones (eq 4). The mild reaction conditions and the tolerance of a broad range of functional groups, which are characteristic of the original Swem oxidation protocol, are retained. The reactions are generally completed in 2-3 h. The desired aldehydes, ketones, or lactones are Isolated in 84-90% yields, while fluorous sulfide 2 is separated from the reaction mixture by continuous extraction and is oxidized to sulfoxide 1 for reuse. 

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... 

Table 8.1 Hydrogen peroxide oxidation of sulfides to sulfoxides in fluorous phase .

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