Ozone: A versatile oxidizing agent in academic syntheses and industrial processes

Abstract

(A) Oxidative Cleavage of Double Bonds: Ozone is largely used in the cleavage of double bonds of cyclic and acyclic alkenes to furnish aldehydes, dialdehydes or carboxylic acids, in high yields, as in the synthesis of adipic acid and fatty acids.5a (Chemical Equation Presented). (B) Ozonolysis of Unsaturated Organotrifluoroborates: Recently, Molander and Cooper described an elegant method to prepare oxo-substituted organotrifluoroborates by ozonolysis. This strategy permitted the introduction of carbonyl functionality into organoboron reagents in good to high yields.4 These reagents can be used to increase the molecular complexity in other transformations, such as cross-coupling.7 (Chemical Equation Presented). (C) Ozonolysis of Morita-Baylis-Hillman (MBH) Adducts: The ozonation of aliphatic MBH adducts was described by Doutheau and co-workers, who prepared highly functionalized α-keto esters in high yields.5b Recently, Coelho and co-workers expanded this method to aromatic derivatives and established an expeditious selective approach for the preparation of α,β-dihydroxy esters. 5c (Chemical Equation Presented). (D) Selective Cleavage of Double Bonds (Synthesis of Eplerenone): The chemical research division of Pfizer reported a new approach to prepare 1, an intermediate in the synthesis of eplerenone.8 They used highly regioselective ozonolysis conditions to obtain a carboxylic acid function from the furan ring. Intermediate 1 was obtained in high overall yield (82%), in large scale (100 g) after standard crystallization. (Chemical Equation Presented). (E) Selective Oxidative Cleavage of Silyloxyalkene: Heathcock and Clark showed the potential of ozone in the highly selective oxidation of silyloxyalkenes 2 to lactones 3, in high yields.9 Avery's group used a similar strategy in the last step of the stereoselective total synthesis of (+)-artemisinin from (R)-(+)-pulegone. 10 (Chemical Equation Presented). (F) Ozone in Large-Scale Synthesis: The Pfizer process research group prepared bisulfite 4 via an ozonolysis reaction. After experimental optimization, the ozonolysis step was carried out on a three-kilogram scale. The synthesis was performed in 61% overall yield from 2-indanone (5), and the product was used as a surrogate aldehyde in a reductive amination reaction.11 (Chemical Equation Presented). © Georg Thieme Verlag Stuttgart.