Oxidation to Aldehyde and Ketones

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View circa Jan 2014

Cr reagents used for oxidation seem to have been replaced largely by greener reagents, although publications persist on ‘green’ variants of Cr (VI) oxidants.

MnO2 and hypervalent iodine oxidations are still fairly common in early phase development/med chem publications and occur frequently in early routes – these reagents tend to be designed out or replaced with greener ones. Hypervalent iodine reagents do still find use with some complex substrates. Variants of catalytic hypervalent iodine reagents are now appearing. The most common oxidation pathways use TEMPO-type catalysts with a terminal oxidant, the Corey- Kim method, and activated DMSO variants (Swern oxidation). A very popular DMSO activating agent for larger scale work is the pyridine SO3 complex.

Chlorine –pyridine, Ba(MnO4)2 and, to a lesser extent, nickel peroxide [probably NiO(OH)2] find little use as oxidants for the synthesis of aldehydes or ketones. Over the past five years, there has been an exponential increase in the number of publications related to the use of metals and air (O2) or H2O2, presumably due to the good atom economy and ease of processing. Process intensification and flow chemistry are used to minimize issues with exothermic chemistry and hazards associated with flammable solvents and oxidants. Many more biocatalytic approaches to alcohol oxidation are also being developed.

General Review

Caron, S.; Dugger, R. W.; Gut Ruggeri, S.; Ragan, J. A.; Brown Ripin, D. H. Large-Scale Oxidations in the Pharmaceutical Industry. Chem. Rev. 2006, 106 (7), 2943–2989.

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