Sulfoxide activation

This class of donor is activated by soft Lewis acids, such as copper triflate at room temperature, and despite their hydrolytic instability, they appear inert to conditions of sulfoxide activation, TMSOTf or Tf20 (Scheme 4.53). Activation is achieved with stoichiometric promoter in the presence of the acceptor alcohol, and although the mechanism has not been investigated, presumably it proceeds via coordination followed by collapse to a stabilized oxacarbenium ion. The method is compatible with standard glycosidation solvents such as dichloromethane, acetonitrile and diethyl ether, and ester-directed couplings do not lead to orthoesters, perhaps as a result of the presence of the Lewis acid promoter [303,304]. 

Diastereoselective glycosidation of a sulfoxide at the anomeric center as the gly-cosyl acceptor. The sulfoxide activation is achieved using Tf20. 

Ube Industries LtdinYamaguchi, Japan, and Kyoto University investigated the Swern oxidation for pharmaceutical intermediates [57,58]. In this reaction, alcohols are oxidized to carbonyl compounds using dimethyl sulfoxide. The reaction variant using dimethyl sulfoxide activated by trifluoroacetic anhydride (shown below) has found industrial application, but is limited to low-temperature operation (—50 °C or below) to avoid decomposition of an intermediate. 

To increase the enantioselectivity of these myoglobin metalloenzymes, Lu and co-workers have successfully utilized a covalent linkage approach [62], In an earlier attempt a Mn(III)-salen complex was incorporated into apo-myoglobin by mutating residue 103 to cysteine, followed by modification with a methane thiosulfonate derivative of Mn(III)(salen) (Figure 5.16). This catalyst showed sulfoxidation activity however, the ee was only 12 %. As such a low ee might be a result of the ability of the bound ligand to exist in multiple conformations within the protein cavity, it was hypothesized that the rotational freedom of the salen complex could be limited if it was anchored at... 

Ten Brink, H.B., Holland, H.L., Schoemaker, H.E., van Lingen, H. and Wever, R. (1999). Probing the scope of the sulfoxidation activity of vanadium bromoperoxidase from Ascophyllum nodosum. Tetrahedron Asymmetry, 10,4563-4572. 

The relatively mild conditions of this dimethyl sulfoxide activation method have been used to good effect to oxidize many sensitive substrates. For instance the alcohol (20 equation 10) was smoothly converted to the aldehyde without any racemization occurring, which can be a problem with other oxidizing systems. Similar advantages were noted in the oxidation of the alcohol (21), thus demonstrating the compatibili of some sensitive protecting groups to the reaction conditions. ... 

The above discussion has concentrated upon the reagents used, but it is equally of value to comment on the substrate, particularly in reactions for which other oxidation methods have been reported to fail. A good example is the oxidation of the iron-carbonyl complex (31) to the ketone (32 equation 14). The use of dimethyl sulfoxide activated with sulfur trioxide-pyridine complex gave a 70% yield of the product, in contrast to the use of the Pfitzner-Moffatt procedure (dimethyl sulfoxide-DCC) or the chromium... 

Despite this, some useful oxidations have been achieved using the method, such as that of yohimbine to yohimbinone in 85% yield, which compares well with that achieved by using dimethyl sulfoxide activated with dicylohexylcarbodiimide. The method has also been successfully applied to the oxidation of carbohydrates, as shown by the formation of (11 equation 6), and aromatic a-diketones can be efficiently prepared using this method by oxidation of the corresponding acyloin products. Unfortunately this methodology cannot be extended to the more useful aliphatic diketones. ... 

An area of recent intense synthetic endeavor has been in the syntiiesis of the avermectins and milbe-mycins, which contain a range of highly reactive functionalities such as the spiroacetal group, double bonds, and epimerizable centers. However, dimethyl sulfoxide activated oxidations, most notably the Swem variation, have teen useful in this area of chemistry. For example, the sensitive spiroacetal (34) gave 92% of the derived aldehyde using dimetiiyl sulfoxide-oxalyl chloride-triethylamine at -SO C (equation 15). ... 

The oxidation of diols having alcoholic groups of the same nature, for example, both alcoholic groups are primary, secondary, allylic, or benzylic, is usually carried out at both groups to yield dialdehydes [832] or diketones [552], Such reactions are achieved by chromium trioxide [582], barium manganate [832], dimethyl sulfoxide activated with acetic anhydride [1013], and others (equations 284 and 285). 

Several studies have shown an increased frequency of penicillamine adverse effects in patients with low sulfoxidation activity, especially with regard to proteinuria and probably thrombocytopenia and myasthenia gravis (SED-12, 547) (3,196,387,388). The sulfoxidation capacity is expressed as the sulfoxidation index, calculated as the percentage of administered 5-carboxymethyl-L-cysteine (750 mg), excreted as sulfoxides in the urine in 8 hours. A sulfoxidation index above 6% is taken as indicative of relative impairment of sulfoxidation capacity. 

Vinyl sulfoxides also partake in additive Pummerer reactions. Of particular interest in this category are cases where the sulfoxide activating agent also provides the internal nucleophile. Two general pathways for such vinylogous additive Pummerer reactions are presented in Scheme 36. ... 

Roa-Gutierrez, F., Liu, H.-J. Use of silyl chlorides as dimethyl sulfoxide activators for the oxidation of alcohols. Bulletin of the Institute of... 

The condensation of aromatic and aliphatic aldehydes with sulfoxide-activated methylenes like phenylsulfmylacetonitriles and phenylsulfmylacetates selectively forms a-sulfinyl-a,3-unsaturated carbonyl compounds (144) with the alkyl or aryl group trans to the sulfinyl group (see Section 1.11.2.5). 2 Oxidations of (144) with m-chloroperbenzoic acid yield the unsaturated ( )-sulfones... 

Oxidations using dimethyl sulfoxide activated by various reagents began with discoveries by Komblum and co-workers that primary tosylates and certain a-bromo ketones could be converted into aldehydes and glycoxals, respectively, by treatment with dimethyl sulfoxide as the oxidising agent. This was followed by the discovery several years later by Pfitzner and Moffatt that alcohols could be oxidised to carbonyl compounds with dimethyl sulfoxide, dicyclohexylcarbodiimide (DCC) and phosphoric acid at room temperature.2 Eventually the method developed by Swern and co-workers, involving activation of dimethyl sulfoxide with oxalyl chloride, came to be the most synthetically useful and widely applied of these mild oxidation procedures.3-6... 

On treatment with methyl sulfoxide activated by sulfur trioxide and triethylamine, " various partially acetylated hexopyranosides give 4,5-unsaturated 4-deoxy-6-aldehydo pyranosides by oxidation of the primary hydroxyl group. For instance, 131 gives 133 by way of the aldehyde 132. Chromatographically pure methyl 2,3-di-0-acetyl-4-deoxy-6-aZde-... 

Similar vinylog -elimination was observed on pyranoid and furanoid sugar derivatives. Perlin and coworkers described a double j8-elimina-tion on 2,3,4,6-tetra-O-acetyl-a-D-mannopyranose by treatment with methyl sulfoxide activated by sulfur trioxide-pyridine-triethylamine. 

Mancuso A, Huang SL, Swem D (1987) Oxidation of Long-chain and Related Alcohols to Carbonyls by Dimethyl Sulfoxide "Activated" by Oxalyl Chloride. J Org Chem 43 2480... 

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