Swem oxidation

The present section reviews the recent apphcations in the activation of dimethyl sulfoxide, with the aim of identifying alternative milder and more practical methods for the oxidation of hydroxylic compounds. Thereafter, we focus on oxalyl dichloride, the classical Swem reagent, on diphosgene and triphosgene, as well as on alternative non-chlorine activation methods. 

Oxalyl chloride reacts with dimethyl sulfoxide at low temperatures to initially form adduct 1790a, which collapses to a dimethylchlorosulfonium species 1790b. Reaction of 1790b with an alcohol at 78 °C produces the alkoxysulfonium ion 1791, which is converted into the product by reaction with an amine base to give yhde 1792, which further reacts intramolecularly to give the carbonyl product. 

A series of substituted ortho-phthalaldehydes has been prepared under mild conditions in respectable yields by oxidation of the corresponding dimethanols using oxalyl chloride activated DMSO [1343]. 

Primary and secondary alcohols have been oxidized under Swem conditions to furnish the ketones 1793 [1375] and 1794 [1376] as well as the aldehyde 1795 [1377]. 

Typical procedure. (1jff,3aa,9ajff)-Decahydro-l,8,8-trimethyl-3a-[(2-trimethylsilyl)ethoxy-methoxy]-6H-cyclopentacyclooctan-6-one 1793 [1375] Dimethyl sulfoxide (0.536 mL, 0.397 g, 5.10 mmol) was added dropwise to a stirred solution of oxalyl chloride (0.213 mL, 0.311 g, 2.45 mmol) in didiloromethane (20 mL) at —78 °C. The mixture was stirred for 15 min at —78 °C, and then a solution of (l) ,3aa,9a/ )-decahy-dro-l,8,8-trimethyl-3a-[(2-trimethylsilyl)ethoxymethoxy]-3aH-cyclopentacyclooctan-6-0I (0.74 g cmde, ca. 2.04 mmol) didiloromethane (5 mL) was added dropwise by means of a syringe. After stirring for a further 15 min at 78 °C, N,N-diisopropy-lethylamine (2.83 mL, 2.10 g, 16.3 mmol) was added, and the reaction mixture was 

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The widely used Moifatt-Pfltzner oxidation works with in situ formed adducts of dimethyl sulfoxide with dehydrating agents, e.g. DCC, AcjO, SO], P4O10, CCXTl] (K.E, Pfitzner, 1965 A.H. Fenselau, 1966 K.T. Joseph, 1967 J.G. Moffatt, 1971 D. Martin, 1971) or oxalyl dichloride (Swem oxidation M. Nakatsuka, 1990). A classical procedure is the Oppenauer oxidation with ketones and aluminum alkoxide catalysts (C. Djerassi, 1951 H. Lehmann, 1975). All of these reagents also oxidize secondary alcohols to ketones but do not attack C = C double bonds or activated C —H bonds. 

The aldehyde function at C-85 in 25 is unmasked by oxidative hydrolysis of the thioacetal group (I2, NaHCOs) (98 % yield), and the resulting aldehyde 26 is coupled to Z-iodoolefin 10 by a NiCh/CrCH-mediated process to afford a ca. 3 2 mixture of diaste-reoisomeric allylic alcohols 27, epimeric at C-85 (90 % yield). The low stereoselectivity of this coupling reaction is, of course, inconsequential, since the next operation involves oxidation [pyridinium dichromate (PDC)] to the corresponding enone and. olefination with methylene triphenylphosphorane to furnish the desired diene system (70-75% overall yield from dithioacetal 9). Deprotection of the C-77 primary hydroxyl group by mild acid hydrolysis (PPTS, MeOH-ClHhCh), followed by Swem oxidation, then leads to the C77-C115 aldehyde 28 in excellent overall yield. 

New procedures to the formation of l,4-dioxa-7,l 1-dithiacyclotridecan-9-ol and 1,4,7-trioxa-10,14-dithiacyclohexadecaen-12-ol utilized 2,3-dibromopropanol with either (CH2OCH2CH2SH)2 or 0(CH2CH20CH2CH2SH)2 with Li2C03 in aqueous EtOH the procedure was shown to proceed via an oxirane intermediate <06CHC206>. The convenient oxidation of the above tridecan-9-ol to the l,4-dioxa-7,ll-dithiacyclotridecan-9-one was accomplished by a Swem oxidation at low (-70 °C) temperatures the alkylation and acylation of the ring alcohol moieties were also reported therein. 

Stilbenes, photocyclization of, 30, 1 StiUe reaction, 50, 1 Stobbe condensation, 6, 1 Substitution reactions using organocopper reagents, 22, 2 41, 2 Sugars, synthesis by glycosylation with sulfoxides and sulfinates, 64, 2 Sulfide reduction of nitroarenes, 20, 4 Sulfonation of aromatic hydrocarbons and aryl halides, 3, 4 Swem oxidation, 39, 3 53, 1... 

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