Visible‐Light Photoredox‐Catalyzed Remote Difunctionalizing Carboxylation of Unactivated Alkenes with CO₂

Abstract

Remote difunctionalization of unactivated alkenes is challenging but a highly attractive tactic to install two functional groups across long distances. Reported herein is the first remote difunctionalization of alkenes with CO2. This visible‐light photoredox catalysis strategy provides a facile method to synthesize a series of carboxylic acids bearing valuable fluorine‐ or phosphorus‐containing functional groups. Moreover, this versatile protocol shows mild reaction conditions, broad substrate scope, and good functional‐group tolerance. Based on DFT calculations, a radical adds to an unactivated alkene to smoothly form a new carbon radical, followed by a 1,5‐hydrogen atom‐transfer process, the rate‐limiting step, generating a more stable benzylic radical. The reduction of the benzylic radicals by an IrII species generates the corresponding benzylic carbanions as the key intermediates, which further undergo nucleophilic attack with CO2 to generate carboxylates.

Light‐Mediated Carboxylation Using Carbon Dioxide

“…Very recently, Yu and co‐workers reported a reaction of unactivated alkenes with CO 2 via visible‐light photoredox catalysis to afford series of carboxylic acids (Scheme 18). [35] This reaction combines radical attack to alkenes, hydrogen atom transfer (HAT) and remote C−H functionalization. The radical precursors, including CF 3 SO 2 Na, CHF 2 SO 2 Na, and HP(O)Ph 2 , are used in the reaction.…”

Spirocyclizative Remote Arylcarboxylation of Non-Activated Arenes with CO2 via Visible-Light-Induced Reductive Dearomatization

“…The structure of 2 was confirmed by X-ray analysis, representing a formal remote C-H carboxylation with CO2. [96][97][98] Control reactions revealed that no product was detected in the absence of either a PC or light, indicating the reaction was induced by light (entries 2 and 3). A significant decrease in the yield was observed when the reaction was carried out under nitrogen atmosphere (entry 4), suggesting that some CO2 could be produced from the oxidation of 4-CO2K-HE.…”

“…Interestingly, dearomatization occurred predominantly at non-activated phenyl ring via 6-exo-trig cyclization rather than at the activated indole ring's C2-C3 double bond via 5-exo-trig in previous study with the same substrate, 90 leading to spirocyclic product 55 with a formal remote C-H carboxylation. [96][97][98] The rationale for this chemoselectivity is not clear at present. Initially, the iodide substrate was also employed, but it was less effective than its bromide analog (55).…”

Radical‐Based Synthesis and Modification of Amino Acids

“…Finally, the groups of Jamison [27] and Yu [28] have reported the synthesis of α‐AAs by α‐C−H functionalisation. Whereas Jamison's strategy proceeds by a radical–radical coupling of α‐amino radicals with CO 2 .− , Yu's proceeds by an intramolecular 1,5‐HAT, which generates the key α‐amino radical that can be subsequently reduced to the corresponding carbanion and trapped by CO 2 (Scheme 8 B,C).…”