Oxidative Deprotection ofp-Methoxybenzyl Ethers via Metal-Free Photoredox Catalysis

Abstract

An efficient and greener deprotection method for p-methoxybenzyl (PMB) ethers using a metal-free visible light photoredox catalyst and air and ammonium persulfate as the terminal oxidants is presented. Various functional groups and protecting groups were tolerated in the developed method to achieve good to excellent yields in short reaction times. Significantly, the developed method was compatible with PMB ethers derived from primary, secondary, and tertiary alcohols and a gram-scale reaction. Mechanistic studies support a proposed reaction mechanism that involves single electron oxidation of the PMB ether.

Efficient Greener Visible‐Light‐Catalyzed Debenzylation of Benzyl Ethers and Esters: A Gateway to Wider Exploitation of Stable Benzyl Protecting Groups

“…Unavailability of alternative milder and reliable debenzylation options limits the widespread use of benzyl protection of hydroxyl group in multistep synthesis. In order to avoid hydrogenolytic debenzylation, chemist prefer to use p ‐methoxy benzyl (−PMB) analogue as hydroxyl protecting group as it comes with an easy mild deprotection options [14c] . However, hydroxyl protection using −OPMB ethers suffer from serious instability issue even in mild acid like trifluoroacetic acid.…”

“…Therefore, finding an alternative strategy for deprotection of stable benzyl protection can provide an excellent tool in the hand of synthetic chemists. Though, many deprotection strategies recently have been developed for more activated PMB system, [14b–c,15] comparatively meagre success has been achieved for inactivated benzyl system [16] . Toshima et.…”

Visible-Light-Mediated Oxidative Debenzylation Enables the Use of Benzyl Ethers as Temporary Protecting Groups

“…Compared with benzyl ethers, p -methoxybenzyl (PMB) ethers can be selectively cleaved using mild stoichiometric oxidants. ,− Photoredox catalysis was used to selectively cleave PMB ethers (Scheme a). − Benzyl ethers ( E Bn‑O‑Me = 2.20 V vs saturated calomel electrode (SCE)) have a significantly higher oxidation potential compared with PMB ethers ( E PMB‑O‑Me = 1.60 V vs SCE) and are stable during the photocatalytic PMB cleavage. − …”

“…Full conversion of the starting material and excellent selectivity toward the desired product ( 1b ) were achieved using stoichiometric amounts of 2,3-dichloro-5,6-dicyano-1,4-benzoquinone (DDQ) ( E 3 DDQ*/DDQ –• = 3.18 V vs SCE) and green-light irradiation (525 nm) in wet dichloromethane (Table , entry 1). In contrast with photochemical PMB deprotection, − an additional H-atom acceptor is not required, as the single electron transfer oxidation and the hydrogen abstraction are executed by DDQ upon irradiation . The irradiation source is crucial for achieving high selectivity.…”

Chemoselective Oxidation ofp-Methoxybenzyl Ethers by an Electronically Tuned Nitroxyl Radical Catalyst

“…The PMB group has been widely used as a protecting group for alcohols, as it can be easily introduced via various methods and removed using common oxidizing agents. For the oxidative deprotection of PMB ethers, stoichiometric amount of 2,3-dichloro-5,6-dicyano-1,4-benzoquinone (DDQ) or more than 2 equiv of ceric ammonium nitrate (CAN) are usually employed, although various other methods have been reported . These common methods are not environmentally benign, as DDQ has the potential to liberate HCN and the deprotection by CAN requires more than 2 equiv of cerium, which is a rare-earth metal.…”