Moffatt-Swem oxidation

The scope of the 2-azadiene intramolecular Diels-Alder cyclization, employed for the synthesis of the daphniphyllum alkaloids, has been further investigated by Heathcock et al.[76j. The protocol involves Moffatt-Swem oxidation of the 1,5-diol to the dialdehyde, and treatment of the crude methylene chloride solution with ammonia followed by solvent exchange from methylene chloride to a buffered acetic add solution. The cydopentyl ring, quaternary carbon and tertiary carbon centers in... 

Due to the modularity and availability of a number of functional elements, multistep reactions can be set up, studied, optimized, and combined with separation techniques. A number of process applications have been described by industrial and university laboratories, for example, the investigation of organic textbook reactions [27], the Moffatt-Swem oxidation [28], Dibal-H reduction [29], phase transfer catalysis [30], and gas/liquid separation techniques such as desorption [31] as well as liquid/liquid separation by a hydrocyclone [32], Technical details of the MMRS can be found elsewhere and will not be described in more detail here [26]. 

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. 

Sulfoxides (essentially DMSO) can be used for oxidation of alcohols to v carbonyl compounds as in the Moffatt, Swem and related oxidations [237,... 

T. T. Tidwell, Oxidation of Alcohols to Carbonyl Compounds via Alkoxysulfonium Ylides The Moffatt, Swem, and Related Oxidations, Org. React. 1990, 39, 297-572. 

Other oxidation reactions using DMSO as an oxidant include the Pfitzner-Moffatt Oxidation (DMSO/dicyclohexylcarbodiimide), Swem oxidation (DMSO/oxalyl chloride or trifluoroacetic anhydride), Onodera oxidation (DMSO/phosphorus pentoxide), Parikh-Doering Oxidation (DMSO/pyridine-sulfur trioxide), Corey-Kim Oxidation (dimethyl sulfide/Ai-chlorosuccinimide), and Liu oxidation (DMSO/phenyl dichlorophosphate). 

Application to the synthesis of a-hydroxy ketones E. J. Corey, C. U. Kim, Tetrahedron Letters 1974,287 of 1,3-dicarbonyl compounds S. Katayama etal, Synthesis 1988, 178 J. T. Pulkkinen etal, J. Org. Chem. 61, 8604 (1996). Cf. Pfitzner-Moffatt Oxidation Swem Oxidation. 

Tidwell TT (1990) Oxidation of alcohols to carbonyl compounds via alkoxysulfonium ylides the moffatt, swem, and related oxidations. Org React 39 297-555... 

However, relatively less use of the reaction appears to have been made in the preparation of the higher terpenes, but some notable exceptions to this are the use of a Moffatt oxidation as a key step in an unusual approach to hydrazulene-based sesquiterpenes, (42) to (43 equation 17), and the use of the Swem variation in the gibberrellin synthesis (44) to (45 equation 18). 

The Pfitzner-Moffatt oxidation utilises 1,3-dicyclohexylcarbodiimide as the DMSO activator in the presence of acid to afford oxidation of alcohols to carbonyls.2,24,25 Initial work was carried out on steroids and thymidine residues although the procedure has since been found to be applicable to a large range of alcohols. In the following example, the Pfitzner-Moffatt method was used as an alternative to the Swem reaction which had resulted in the formation of an unwanted a-chloroketone (see later).26 Other oxidation procedures were attempted (PDC, PCC, Dess-Martin periodinane) however the Pfitzner-Moffatt gave the best, albeit modest, yield. 

Reactivity/selectivity studies M. Marx, T. T. Tidwell, J. Org. Chem. 49, 788 (1984). Reviews A. J. Mancuso, D. Swem, Synthesis 1981, 165-185 passim T. T. Tidwell, Org. React. 39, 297-572 passim (1990). Cf. Corev-Kim Oxidation Pfitzner-Moffatt Oxidation. 

The Swem-Moffatt oxidation in a continuous-flow microreactor system was investigated by Organon N.V., The Netherlands [49]. 

Then, a pilot plant with a capacity of lOt/a was built for the Swem-Moffatt oxidation [71,73]. The yield of the batch process is 83% at —70°C, whereas the microchemical process achieved a yield of 88% at 20 °C. The pilot plant was operated under stable reaction conditions for a long run with similar product yields as in the laboratory experiment (see Figure 11.22). 

Dimethyl Sulfoxide and elimination by base (eq 3), a mechanism closely related to that of the Swem and Moffatt oxidations. ... 

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