Visible Light-Mediated Oxidative Debenzylation

Abstract

Protecting groups are key in the synthesis of complex molecules such as carbohydrates to distinguish functional groups of similar reactivity. The harsh conditions required to cleave stable benzyl ether protective groups are not compatible with many other protective and functional groups. The mild, visible light-mediated debenzylation disclosed here renders benzyl ethers orthogonal protective groups. Key to success is the use of 2,3-dichloro-5,6-dicyano-1,4-benzoquinone (DDQ) as stoichiometric or catalytic photooxidant such that benzyl ethers can be cleaved in the presence of azides, alkenes, and alkynes. The reaction time for this transformation can be reduced from hours to minutes in continuous flow. <br>

Excited‐State 2,3‐Dichloro‐5,6‐dicyano‐1,4‐benzoquinone (DDQ*) Initiated Organic Synthetic Transformations under Visible‐Light Irradiation

“…was reported by Cavedon and coworkers [45] in 2020. This protocol is applicable to a variety of substrates containing acetyl, benzoyl and isopropylidine protecting groups and smoothly deprotected them in less than 4 h in good yield.…”

“…The authors also tested a continuous flow approach for the debenzylation of C(3)-benzyl-glucofuranose, which reduced the reaction time significantly to three minutes. [45]…”

“…The 3 DDQ*-assisted one-electron oxidation of the fluoroarene (41) affords the corresponding radical cation intermediate (44). A reaction between 44 and a nucleophilic azole (42) gives a new carbon-centered radical intermediate (45). The intermediate 45 is reduced electrochemically yielding anion 46 responsible for formation of product (43) after loss of the fluoride anion.…”

“…A DDQ‐assisted protocol for the oxidative debenzylation of benzyl ethers ( 92 ) under visible‐light irradiation (Scheme 37) was reported by Cavedon and coworkers [45] in 2020. This protocol is applicable to a variety of substrates containing acetyl, benzoyl and isopropylidine protecting groups and smoothly deprotected them in less than 4 h in good yield.…”

Chromoselective Photocatalysis Enables Stereocomplementary Biocatalytic Pathways**

“…We recently realized that the choice of the wavelength is crucial for high selectivities in metallaphotocatalytic cross couplings using a heterogeneous carbon nitride material, which is made from urea and oxamide in molten salt (CN‐OA‐m) [5b,c, 7] . While this can be rationalized by a purely kinetic effect, there is also evidence that a wavelength‐controlled generation of excited species with different oxidation potentials might be responsible for this phenomenon.…”