Carbodiimides sulfoxide

The facile and selective oxidation of both primary and secondary hydroxy groups with certain nucleotides led Pfitzner and Moffatt (48) to explore the scope of the carbodiimide-methyl sulfoxide reagent with steroid and alkaloid alcohols. Relatively minor differences were apparent in the rate of oxidation of epimeric pairs of 3- and 17- hydroxy steroids whereas the equatorial lLx-hydroxyl group in several steroids was readily oxidized under conditions where the axial epimer was unreactive [cf. chromic oxide oxidation (51)]. 

The activation of DMSO toward the addition step can be accomplished by other electrophiles. All of these reagents are believed to form a sulfoxonium species by electrophilic attack at the sulfoxide oxygen. The addition of the alcohol and the departure of the sulfoxide oxygen as part of a leaving group generates an intermediate comparable to C in the carbodiimide mechanism. 

The aldehyde 38 was obtained from 35, by way of 36 and 37, by the carbodiimide—dimethyl sulfoxide oxidation procedure52 in the presence of 3-(3-dimethylaminopropyl)-l-ethylcarbodiimide hydrochloride (EDAC)53 and dichloroacetic acid. It was isolated in the form of its crystalline 1,3-diphenylimidazolidine derivative (39) by trapping the freshly prepared aldehyde 38 with N,N -diphen-ylethylenediamine. (This reagent was developed by Wanzlick and Lochel54 for the selective derivatization of aldehydes, and has been exploited for the isolation of nucleoside 5 -aldehydes55 and other aldehydo derivatives of carbohydrates by Moffatt and coworkers.52(b))... 

The dimethyl sulfoxide (Me2SO)-dicyclohexyl carbodiimide (DCC) method described by Pfitzner and Moffatt24 opened a route to keto derivatives of aldopentosylpyrimidines,2,25 as well as to many keto derivatives of hexosyl-purines3,7,26-31 and -pyrimidines.30,32,33 An alternative proposed by Swern and coworkers,34 requiring the presence of oxalyl chloride as an activating agent, has been used to prepare 4-keto-lyxo-hexose C-nucleosides.13... 

C-(w-propyl)-N-phenylnitrone to N-phenylmaleimide, 46, 96 semicarbazide hydrochloride to ami-noacetone hydrochloride, 45,1 tetraphenylcyclopentadienone to diphenyl acetylene, 46, 44 Alcohols, synthesis of equatorial, 47, 19 Aldehydes, aromatic, synthesis of, 47,1 /8-chloro-og3-unsaturated, from ketones and dimethylformamide-phosphorus oxychloride, 46, 20 from alkyl halides, 47, 97 from oxidation of alcohols with dimethyl sulfoxide, dicyclohexyl carbodiimide, and pyridinium trifluoroacetate, 47, 27 Alkylation, of 2-carbomethoxycyclo-pentanone with benzyl chloride, 45, 7... 

Moffatt, J. G. Sulfoxide-carbodiimide reactions. X. Mechanism of the oxidation reaction. J. Org. Chem. 1971, 36,1909-1913. 

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]. 

Sulfoxide-Carbodiimide Reactions. XI. Scope of the Oxidation Reaction. 

Nitronium salts as discussed react extremely readily with ir-donor aromatic compounds as well as with alkenes and alkynes (vide infra). They also show high reactivity towards -donors, such as alcohols, ethers, amines, amides, imides, carbodiimides, oximes, hydrazones, sulfides, sulfoxides, halides, and phosphines. However, their reactivity toivards cf-donors is understandably much lower. 

The original Pfittner-Moffatt procedure for alcohol oxidation by activated dimethyl sulfoxide utilized dicyclohexylcarbodiimide (DCC) and a source of protons such as polyphosphoric acid or pyridinium tri-fluoroacetate. The use of strong acids such as the common mineral acids must be avoided since, although acidic conditions are initially required, the reaction must readily become basic in the later stages of the process. Mechanistically it is reasonable to suggest that the activation follows the pattern whereby initial attack of the nucleophilic sulfinyl oxygen of dimethyl sulfoxide, with the protonated carbodiimide, forms a sulfonium isourea. This is followed by displacement of dicyclohexylurea by the alcohol to form an alkoxysulfonium salt. Base treatment of this salt forms an ylide, which collapses via the proven cyclic mechanism to the carbonyl compound and dimethyl sulfide (Scheme 4). 

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