Protection and deprotection protocols that enable orthogonal strategies are of utmost importance in the total synthesis of complex molecular scaffolds. This concept is emphasized in the chemical synthesis of oligosaccharides, where selective coupling is achieved by the appropriate choice of orthogonally protected building blocks that carry temporary (tPG) and permanent protecting groups (pPG).
The limited availability of non-participating, temporary PGs represents a bottleneck in carbohydrate synthesis. Benzyl ethers are suitable non-participating PGs, but they are regarded as pPG due to their harsh and non-orthogonal deprotection conditions (Catalytic hydrogenolysis, Birch reduction).
We developed a mild, visible light-mediated debenzylation protocol using 2,3-dichloro-5,6-dicyano-1,4-benzoquinone (DDQ) as photo-oxidant that can be either used in stoichiometric or catalytic amounts. A high functional group tolerance was achieved using 525 nm irradiation as demonstrated for several carbohydrate building blocks equipped with multiple protecting groups. A flow approach can be used to significantly enhance this protocol, reducing the reaction times from hours to minutes. Benzyl ether can be cleaved in presence of, for example, azides, alkenes and alkynes, that are not stable using common deprotection strategies. This protocol enables use of benzyl ether as orthogonal, temporary PG in synthetic chemistry.
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: M. Guberman, P. H. Seeberger, J. Am. Chem. Soc. 2019, 141, 5581-5592, 10.1021/jacs.9b00638.