Epoxidation
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General Overview
Epoxides are versatile intermediates used to construct amino alcohols, diols, hydroxy-thiols and other highly functionalised synthons. The use of chiral epoxides leads to 1,2 difunctionalized chiral products. Epoxides can be isomerised to ketones, but this is less often employed as a synthetic strategy. Epoxides are usually produced via direct oxidation of olefins, although other starting materials have been employed. As with most oxidations, the exothermic nature of the transformation and potential for reagent accumulation mean scale-up needs to be carefully considered with appropriate safety testing. The use of continuous flow technology can be employed to manage exothermic reactions. See Org. Process Res. Dev. 2011, 15, 1464–1469 for the investigation of a H2WO4/H2O2 runaway. A range of methods exists for the direct synthesis of chiral epoxides. Many of these require specific structural features on the substrate to give good ee. Some epoxides can be thermally unstable, especially if concentrated. The epoxy group gives a positive alert in PGI screening, so care should be taken in handling and using epoxides close to the end of a synthetic route to an API.
Green Criteria for Epoxidation
If possible, peroxidation should be carried out catalytically with the safest, highest atom efficient oxidant possible – H2O2 etc. Where possible, the use of halogenated solvents should be avoided. The methods other than alkene epoxidation need to be individually assessed, although telescoping can greatly reduce PMI and energy use if a single solvent and isolation of intermediates can be avoided.
General Reviews on Epoxidation
Catalysis Science & Technology 2013, 3(3), 552-561 This perspective article gives a summary of the most active catalysts for the epoxidn. of some most frequently applied olefins, such as cyclooctene, 1-octene, prochiral olefins and industrially relevant olefins.
Innovative Catalysis in Organic Synthesis 2012, 77-102 A review on recent developments in selective and sustainable oxidns. using peroxides as O donors. Besides metal-catalyzed oxidns., enzyme-catalyzed oxidns. using ROOH are also included.
Chem. Rev. 2005, 105, 1603−1662 Advances in Homogeneous and Heterogeneous Catalytic Asymmetric Epoxidation