Metal-Free Radical-Mediated C(sp³)–H Heteroarylation of Alkanes

Abstract

Herein we disclose a metal-free, N/O-centered radical-promoted Minisci reaction, in which the coupling of various heteroarenes with simple alkanes proceeds under mild conditions. The reaction conditions are neutral; no extra acid is added to preactivate N-heteroarenes in the Minisci reaction. The N-/O-centered radicals are generated directly from amide (TsNHMe) or alcohol (CF3CH2OH) under visible-light irradiation. This green and eco-friendly synthetic process may find potential use in medicinal chemistry.

PIFA‐Mediated Cross‐Dehydrogenative Coupling of N‐Heteroarenes with Cyclic Ethers: Ethanol as an Efficient Promoter

“…HRMS (ESI) Calcd. for C 16 08, 149.29, 147.90, 129.39, 128.93, 125.47, 123.86, 123.00, 117.18, 76.77, 68.97, 33.88, 25.98, 25.55; Spectral data match those previously reported. [9] 2,6-Dimethyl-4-(tetrahydrofuran-2-yl)quinolone (4 h): Colorless liquid, 68 % yield (62 mg); IR (neat) cm À 1 : v˜= 2911, 2851, 1599, 1561, 1439, 1338, 1073, 880, 824, 730, 604, 496; 1 148.59, 146.41, 135.16, 131.08, 129.05, 123.81, 122.00, 117.11, 76.73, 68.94, 33.84, 25.98, 25.40, 21.89 80, 68.99, 33.62, 25.96, 25.39; Spectral data match those previously reported.…”

“…Based on these observations and the fact that ethanol plays an essential role in the reaction (entry 15, Table 1), as well as the established mechanism of PIFA-mediated racial processes, [11,16] especially those with alcohol as the initiator, a plausible reaction mechanism is proposed (Scheme 3). The reaction of PIFA with EtOH provides a hypervalent iodine (III) intermediate I.…”

Updates on hypervalent-iodine reagents: metal-free functionalisation of alkenes, alkynes and heterocycles

“…The N/O-centered radicals are generated from TsNHMe or CF 3 CH 2 OH under visible-light irradiation using PIFA as the HVI reagent (Scheme 70). 128…”

“…The N/O-centered radicals are generated from TsNHMe or CF 3 CH 2 OH under visible-light irradiation using PIFA as the HVI reagent (Scheme 70). 128 The proposed mechanism involves the interaction between PIFA and amide/alcohol to afford intermediates (A) and (B). These two intermediates then generate N-/O-centred radicals (C)/(D) along with an iodanyl radical (P) under visible light irradiation.…”

Metal‐Free Photoinduced Deformylative Minisci‐Type Reaction

“…Recently, we disclosed the photochemical remote C(sp 3 )−H heteroarylation (Minisci reaction) of alcohols and amides mediated by phenyliodine bis(trifluoroacetate) (PIFA) [3] . The protocol was then applied to the intermolecular reaction of heteroarenes with simple alkanes [4] . Nevertheless, the approach suffers from poor site selectivity and is limited to simple symmetric alkanes without the assistance of directing groups.…”