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>

Photocatalytic Cleavage of Trityl Protected Thiols and Alcohols

“…15 16 17 Similarly, we observed only 55% of product 22 , which is attributed to undesired debenzylation events. 19 These selectivity issues were not observed in case of electron-rich benzyl trityl ethers ( 23 , 24 ).…”

“…18 More recently, DDQ photocatalysis was used for chromoselective benzyl ether cleavage in the presence of alkenes, alkynes, and azides. 19 This exceptional functional group tolerance allowed the selective cleavage of benzyl-protected alcohols in the total synthesis of tetrodotoxin by the Trauner group, 20 and in the synthesis of eribulin B by Nicolaou and co-workers. 21…”

Recent Developments in Solid-Phase Glycan Synthesis

“…88 However, the cleavage of Bn ethers suffers from poor compatibility with other functional groups. Gratifyingly, new, mild photooxidative debenzylation methodologies are emerging; 89 their implementation in SPGS could offer an interesting solution to the cleavage of benzyl PGs.…”