Direct Synthesis of Bicyclic Acetals via Visible Light Catalysis

Abstract

Summary Polysubstituted bicyclic acetals are a class of privileged pharmacophores with a unique 3D structure and an adjacent pair of hydrogen bond acceptors. The key, fused acetal functionality is often assembled, via intramolecular cyclization, from linear substrates that are not readily available. Herein, we report a formal cycloaddition between cinnamyl alcohols and cyclic enol ethers under ambient photoredox catalysis conditions. Polysubstituted bicyclic acetals can be prepared in one step from readily available building blocks. Employment of sugar-derived enol ethers allows easy access to a library of scaffolds with intriguing conformation and medicinal chemistry potential.

Photocatalysis in the Life Science Industry

“…The application of PRC is not limited to the preparation of N-heterocycles as demonstrated by Roche, Nicewicz, Chen, and Huang who reported the formal cycloaddition of allylic alcohols and enol ethers to access mono-and bicyclic acetals (Scheme 49). 155 Although interesting from a structural perspective due to their conformational rigidity and the two hydrogen bond acceptors, concerns regarding the metabolic stability of acetals limit their application in medicinal chemistry. Nonetheless, preliminary studies by the authors in Mechanistically, the single-electron oxidation (SEO) of the enol ether 69 by the excited photocatalyst gives radical cation 70, which is subsequently trapped by the allylic alcohol to give 71 (Scheme 49).…”

Recent Advances in C–H Functionalisation through Indirect Hydrogen Atom Transfer

“…This makes them excellent reagents for HAT from weak (highly activated) C-H bonds, such as α-amino, benzylic, and allylic C-H bonds, as well as weak heteroatom-hydrogen bonds, such as Si-H and Ge-H. Thiols can also be used to close catalytic cycles/reactions through HAT. However, this application is not covered by this review [220][221][222][223][224][225].…”

Tandem Photooxidation/Acetalization of Alcohols to Acetals/Ketals with Sulfur‐doped Carbon Nitride

“…Therefore, only recently avoiding the use of acids, green solid photocatalytic systems have increasingly been employed to catalyse such transformations in tandem fashion [12,17,22–25] . Also, photocatalytic conversion of aldehyde to acetal with ethanol using TiO 2 and other photocatalysts has shown significant promise [23,25–27] . Nikitas et al.…”

“…[12,17,[22][23][24][25] Also, photocatalytic conversion of aldehyde to acetal with ethanol using TiO 2 and other photocatalysts has shown significant promise. [23,[25][26][27] Nikitas et al showed that thioxanthenone photocatalysts efficiently catalyzed the acetalization of aldehydes using a household lamp. [16] Similarly, Subramanian et al achieved chemoselective acetalization with Ni (II) complexes under neutral conditions.…”