Iron-Catalyzed Oxidative Decarbonylative α-Alkylation of Acyl-Substituted Furans with Aliphatic Aldehydes as the Alkylating Agents

Abstract

A protocol for FeCl2-catalyzed oxidative decarbonylative α-alkylation of acyl furans using alkyl aldehydes as the alkylating agents has been developed. This protocol affords α-alkyl-α-acylfurans in moderate to good yields in a practical and sustainable fashion. Mechanistic studies suggest that the reaction proceeds via generation of an alkyl radical from the alkyl aldehyde, addition of the radical to the furan ring, and subsequent rearomatization.

Advancement in the C–H bond alkylation of (hetero)arenes catalyzed by the most abundant transition metal–iron

“…In a unified approach, Liu and Yin demonstrated the α-alkylation of acyl furans through oxidative decarbonylation using readily available alkyl aldehydes as the alkylating agents (Scheme 30). 132 The reaction constitutes FeCl 2 as a catalyst and DTBP as an oxidant in PhF solvent. Primary aldehydes as well as secondary aldehydes such as cyclamen aldehyde, lilyaldehyde, cyclohexane carbaldehyde, cyclopentane carbaldehyde, 3-vyclohexene-1-carboxaldehyde, isobutyraldehyde, 2-ethylhexanal, 2-ethylbutanal, 2-methylpentanal, and 2-methylbutanal are well tolerated.…”

Photoinduced Metal- and Photosensitizer-Free Decarbonylative C–H Alkylation of Cyclic Sulfamidate Imines

“…Aldehydes are abundant, cheap, and readily available bulk chemicals, which have been regarded as a novel radical alkylating reagent for the selectively decarbonylation alkylation of heteroaromatics including quinoxalin-2­(1 H )-ones, isoquinolines, chromones, imidazopyridines, and Furans . Apart from that, cyclic N -sulfonyl ketimines are also privileged skeletons for applications in pharmaceutical chemistry, showing a wide range of biological activities and pharmacological properties such as STS and HCV NS5b inhibitors and antiproliferative agents (Scheme a).…”

Regioselective Pd-catalyzed α-alkylation of furans using alkyl iodides

“…Evano and Nishikata achieved Cu 21 -and Fe 22 -catalyzed alkylation of heteroarenes with alkyl halides, respectively, via a radical pathway; however the coupling partners were limited to tertiary alkyl halides and only a few furan substrates were reported. Furthermore, Bao and Yin employed an Fe catalyst to achieve the alkylation of furans with alkyl diacyl peroxides 23 and aliphatic aldehydes, 24 respectively, but Bao's protocol is restricted because it involves dangerous peroxides and far in excess usage of furans, and Yin's method is strictly confined to acyl-substituted furan substrates and oxidative conditions. Therefore, general and systemic research focused on developing a convenient, practical and, most importantly, a functional-group-tolerant method for direct alkylation of furans is in high demand.…”