Decarboxylative Hydroalkylation of Alkynes via Dual Copper-Photoredox Catalysis

Abstract

A photoredox strategy for the synthesis of a wide range of allylic amines and ethers from carboxylic acids and alkynes has been developed. This approach relies on the perturbation of the ground-state electronic properties of terminal alkynes through the formation and photoexcitation of copper acetylide intermediates. This process takes place through cooperative copper and organic photoredox catalysis and can be carried out in a stereodivergent manner. Thus, a systematic multivariate HTE screening spotlighted that a switch in the stereochemical outcome can be provoked by choosing an appropriate combination of ligand and base. The developed methodology has been applied to the stereoselective coupling of primary, secondary, and tertiary alkyl radicals with (hetero)aromatic terminal alkynes. As an additional practicality, similar reaction conditions allowed for the use of aromatic amines as radical precursors in a cross dehydrogenative coupling for the direct vinylation of inactivated C−H bonds.

Advancement in Organic Synthesis Through High Throughput Experimentation

“…Another example of HTE with dual catalysis employed a Cu catalyst and 1,2,3,5‐tetrakis(carbazol‐9‐yl)‐4,6‐dicyanobenzene (4CzIPN) photocatalyst for hydroalkylation of terminal alkynes with carboxylic acid precursors. A screen of two Cu sources, four ligands, three bases, and four solvents led to the identification of optimal conditions to form either E and Z alkenes [61] based on the conditions employed (Scheme 4e).…”

Photoredox Dual Catalysis: A Fertile Playground for the Discovery of New Reactivities

“…In 2020, we reported a dual copper‐ and photoredox‐catalyzed decarboxylative hydroalkylation of alkynes (42) leading to Z ‐ or E ‐enriched allylic amines and ethers (43) in a diastereodivergent manner from simple carboxylic acids (41) as radical sources and an organic photocatalyst (Scheme 15). [64] The increased electrophilicity on the alkyne moiety, resulting from irradiation with visible light of the corresponding copper acetylide, allowed to address this synthetic challenge.…”

Recent Advances in Nonprecious Metal Catalysis

“…63 Pericaś and co-workers reported an interesting decarboxylative hydroalkylation of alkynes to prepare a wide array of allylic amines and ethers using Cu/photoredox dual catalysis (Scheme 23). 64 Terminal alkynes were coupled with simple carboxylic acids in a diastereodivergent manner to form the products in good yields with modest Z:E ratios. Highthroughput experimentation techniques were utilized to identify the right combination of ligand (trans-cyclohexane-1,2-diamine), solvent (DMA), and base (CsOAc) for the reaction.…”