Visible‐Light‐Photosensitized Aryl and Alkyl Decarboxylative Functionalization Reactions

Abstract

Despite significant progress in aliphatic decarboxylation, an efficient and general protocol for radical aromatic decarboxylation has lagged far behind. Herein, we describe ag eneral strategy for rapid access to both aryl and alkyl radicals by photosensitized decarboxylation of the corresponding carboxylic acids esters followed by their successive use in divergent carbon-heteroatom and carbon-carbon bond-forming reactions.I dentification of as uitable activator for carboxylic acids is the key to bypass ac ompeting single-electrontransfer mechanism and "switcho n" an energy-transfermediated homolysis of unsymmetrical s-bonds for aconcerted fragmentation/decarboxylation process.

Photosensitized Intermolecular Carboimination of Alkenes through the Persistent Radical Effect

“…Upon exploring the various reaction parameters in line with our previous experience with oxime esters, we found that the oxime ester 1 a provided the desired carboimination product with acrylonitrile ( 2 ) when [Ir(dF(CF 3 )ppy) 2 (dtbbpy)](PF 6 ) ( [Ir‐F] , dF‐(CF 3 )ppy=2‐(2,4‐difluorophenyl)‐5‐trifluoromethylpyridine, dtbbpy=4,4′‐di‐ tert ‐butyl‐2,2′‐bipyridine) was used as the photosensitizer under irradiation with blue LEDs. The desired carboimination product 3 a was afforded in 57 % yield ( 1 H NMR) with complete regioselectivity for the linear C‐radical addition (Table , entry 1).…”

“…Alternatively, oxime esters have also been employed successfully in the photosensitized generation of iminyl radicals through N−O bond homolysis . Recently, we have utilized this distinctive energy transfer (EnT) pathway to develop a general radical decarboxylation process applicable to both aromatic and aliphatic carboxylic acids (Figure B, right) . Nevertheless, all of these approaches are plagued by poor atom economy as either the carboxylate unit or the iminyl unit always become part of the waste stream.…”

“…[26,27] Importantly,the use of benzophenone-based oxime esters is also crucial to shut down unwanted SET reduction pathways,owing to their high reduction potential (E irr red = À2.05 V; Section S2.2), which is inaccessible by most of the commonly used photo(redox) catalysts.The use of an EnT pathway is also advantageous for two reasons:1 )T wo different radicals are concurrently generated in equal rates by NÀOb ond homolysis of the oxime ester,a nd 2) the overall decarboxylation/fragmentation and carboamination steps should be independent of the intrinsic regeneration/turnover of the catalyst in the absence of any redox events.E xpediently,t his method uses highly abundant and stable aliphatic carboxylic acids (via their oxime ester derivative) in ah ighly atom-economic fashion, generating carbon dioxide as the sole byproduct. [28] Upon exploring the various reaction parameters in line with our previous experience with oxime esters, [21] we found that the oxime ester 1a provided the desired carboimination product with acrylonitrile (2) [a] Reaction conditions: 1 (0.15 mmol), 2 (0.10 mmol), [Ir-F] (0.5 mol %) in ethyl acetate (1 mL), irradiation with 30 Wblue LEDs (l max = 455 nm) under an argon atmosphere at room temperature for 5h.Y ields were determined by 1 HNMR analysis using dibromomethane as an internal standard.…”

“…Thea dvantageous generation of two different radicals from NÀOb ond homolysis,c oupled with our continuous interest in EnT catalysis, [22] prompted us to investigate whether both C-centered and N-centered radicals could effectively leverage the vicinal carboimination of alkenes ( Figure 1C). During our previous investigation concerning the decarboxylation of oxime esters, [21] we realized relatively long lifetimes of the benzophenone iminyl radicals through the observation of iminyl byproducts.Considering the triplet energies of the oxime esters of aliphatic carboxylic acids (E T = 45.4 kcal mol À1 ,S ection S2.1 in the Supporting Information), we envisioned that at riplet-triplet energy transfer (TTEnT) from the excited photosensitizer (with E T > 46 kcal mol À1 ) should be thermodynamically favored. Thee xcited oxime ester I would participate in ac oncerted decarboxylation/ fragmentation process to generate aC-centered alkyl radical and N-centered diphenyliminyl radical pair II.…”

“…Thee xcited oxime ester I would participate in ac oncerted decarboxylation/ fragmentation process to generate aC-centered alkyl radical and N-centered diphenyliminyl radical pair II. [21,23] Thel ong lifetime of the diphenyliminyl radical IV should allow the transient alkyl radical to escape the solvent cage and add to the terminal position of the alkene to generate as tabilized radical III.L astly,ahighly selective radical-radical crosscoupling between III and IV would be kinetically feasible based on the persistent radical effect (PRE). [24] However, such ar adical-radical cross-coupling approach possesses numerous challenges connected to potentially unproductive pathways outperforming the desired reaction.…”