Scalable Aerobic Oxidation of Alcohols Using Catalytic DDQ/HNO₃

Abstract

A selective, practical and scalable aerobic oxidation of alcohols is described using catalytic amounts of 2,3-dichloro-5,6-dicyano-1,4-benzoquinone (DDQ) and HNO 3 , with molecular oxygen serving as the terminal oxidant. The method was successfully applied to the oxidation of a wide range of benzylic, propargylic and allylic alcohols, including two natural products, namely carveol and podophyllotoxin. The conditions are also applicable to the selective oxidative deprotection of PMB ethers.

Synthetic applications of hydride abstraction reactions by organic oxidants

“…Variations on the protocol employ photoirradiation, 127 which significantly enhances the rates of the processes, and HNO 3 as a source of NO 2 rather than NO. 128 These reactions are most commonly employed for benzylic and allylic alcohol oxidation and ether cleavage reactions, though Pan described an application to benzylic esterification 129 and Cheng reported oxidative carbon– carbon bond formation 130 using these protocols. Applications to carbon–carbon bond construction in densely functionally molecules has yet to be demonstrated, though the appeal of utilizing aerobic conditions to regenerate DDQ in situ dictates that these conditions should be considered in future reaction design.…”

DDQ as a versatile and easily recyclable oxidant: a systematic review

“…However, that procedure was selectively used for the oxidation of allylic, benzylic, and propargylic alcohols (Scheme 9). 34 The selective oxidation of alcohols has always been a thriving topic of discussion in organic synthesis. Mostly metallic oxidants, such as manganese oxides, hypervalent I 2 and chromium oxides, are used for this purpose.…”

“…However, that procedure was selectively used for the oxidation of allylic, benzylic, and propargylic alcohols ( Scheme 9 ). 34 …”

o-Quinone methide with overcrowded olefin component as a dehydridation catalyst under aerobic photoirradiation conditions

“…These features constitute inherent impediments to eliciting the full synthetic potential of dehydridative catalysis. 4 …”

“…In view of designing a dehydridation catalyst under these circumstances, we became interested in one of the canonical structures of o -quinone methide ( o -QM), which could be regarded as a zwitterionic triarylmethilide ( Scheme 1 ). 5 As triarylmethilide (triarylcarbenium) ion, exemplified by tritylium ion, has been used as a powerful dehydridating reagent, 4 we envisioned that the zwitterionic form of o -QM could have an ability to engage in dehydridation, being transformed to its hydrogenated (reduced) form, o -diarylmethyl arylhydroxide. However, although o -QMs undergo 1,4-addition of various nucleophiles, their capability of accepting a hydride from simple organic molecules, 1,4-reduction reactivity, remains obscure.…”