Asymmetric multifunctionalization of alkynes via photo-irradiated organocatalysis

Abstract

Alkynes represent a family of pivotal and sustainable feedstocks for various industries such as pharmaceuticals, agrochemicals, and materials, and they are widely used as important starting materials for the production of a broad range of chemical entities. Nevertheless, efficient structural elaborations of alkynes in chemical synthesis, especially asymmetric multifunctionalization of alkynes, remain largely unexplored. It is thus imperative to develop new asymmetric synthetic approaches, making use of these richly available chemical feedstocks, and enabling their conversion to value-added chiral molecules. Here, we disclose our findings on highly enantioselective multifunctionalization of alkynes by merging photochemistry and chiral phosphoric acid catalysis. Our reported one-pot synthetic protocol is applicable to all types of alkyne substrates, incorporating all three reactants in a fully atom-economic fashion to produce optically enriched tetrasubstituted triaryl- and diarylmethanes, important structural scaffolds in medicinal chemistry and biological sciences.

Enantioselective synthesis of α,α-diarylketones by sequential visible light photoactivation and phosphoric acid catalysis

“…Undoubtedly, the successful asymmetric one-pot protocol would provide a previously unknown strategy for synthesizing chiral building blocks. Very recently, our group and Lu’s group have successfully constructed chiral quaternary carbon centers using this strategy ( 46 , 47 ). In contrast to the quaternary carbon centers, the chiral tertiary carbon stereocenters at the α-position of the carbonyl group are more challenging.…”

Metal‐Free Visible Light‐Promoted Synthesis of 1,2,2‐Triarylethanones and 2,2‐Diarylethanones: Route Towards Tamoxifen

“…[11] Recently, visible-light-induced CAM reactions have been explored for the synthesis of quaternary carbon centers, demonstrating the great potential of this reaction in multicomponent synthetic strategies (Scheme 1c). [12][13][14][15][16][17] As far as we know, visible-light-induced CAM reactions have not been applied to tertiary carbon construction. The present study describes a novel CAM/transfer hydrogenation one-pot reaction of benzoquinones, alkynes, and Hantzsch ester promoted by visible light and catalyzed by Brønsted acid.…”

Divergent Synthesis of Pentacyclic Isoindolinones Enabled by Sequential Insertion of Two Different Isocyanides and Acid Promoted Cyclization of Ketenimines

“…After completion, we found that both pentacyclic isoindolinone 4a and ketenimine 4a′ had formed as reaction products. Inspired by the well-known Pictet–Spengler reaction and the potential of cumulated double bonds to experience intramolecular cyclization, 4 mL of 0.1 M HCl solution was subsequently added, causing 4a′ to efficiently undergo an intramolecular cyclization reaction, forming 4a in a total yield of 60%. Encouraged by this phenomenon, we further optimized the reaction conditions, the results of which are summarized in Table (for details, see Tables S1–S4 in the Supporting Information).…”