Dehydrative condensation of carbonyls with non-acidic methylenes enabled by light: synthesis of benzofurans

Abstract

Condensation of carbonyls with non-acidic methylenes such as those adjacent to heteroatoms and allylic types to generate C[double bond, length as m-dash]C bonds is challenging but highly desirable. Inventing novel methods that can accomplish such condensations can enrich synthetic chemists' toolbox. Herein, we report a simple, clean, and high yielding protocol promoted by light to achieve condensation of non-acidic methylenes with carbonyls. As examples to demonstrate the power of this methodology, one class of ubiquitous and highly important heterocycles, i.e. benzofurans, were synthesized with broad functional group compatibility. Furthermore, intermolecular condensations were also briefly investigated.

Simple and Clean Photo-induced Methylation of Heteroarenes with MeOH

“…It has been documented that triplet carbonyls can abstract hydrogen atoms, especially those adjacent to heteroatoms (such as the O atom in ethers and alcohols), to produce the hydroxyalkyl radical. 44,45 Inspired by this and following our continued interest in photochemistry as a greener alternative to traditional transition-metal-catalyzed chemistry, [46][47][48][49][50][51][52][53][54] we anticipated that simply adding ketones into the reaction system would increase the generation rate of hydroxymethyl radical 15 (,CH 2 OH) because, under light irradiation, triplet ketone would be able to abstract the a-H of MeOH efficiently, 45 eventually leading to the efficient formation of direct-methylation product (16). Different from Jin and MacMillan's system 34 involving iridium photo-redox catalyst and odorous thiol organocatalyst, both of which are either expensive or not friendly to handle, we expected this system to avoid external catalysts and be driven solely by the solvent's intrinsic properties (Scheme 2B).…”

Synthesis of benzofurans from the cyclodehydration of α-phenoxy ketones mediated by Eaton’s reagent

“…The NMR spectra are in good agreement with the literature. 75 1 H NMR (600 MHz, CDCl 3 ): δ = 7.63 (dd, J = 7.7, 0.6 Hz, 1H), 7.58 − 7.51 (m, 5H), 7.45 − 7.40 (m, 1H), 7.35 − 7.30 (m, 1H), 7.30 − 7.26 (m, 1H), 2.95 (q, J = 7.5 Hz, 2H), 1.42 (t, J = 7.6 Hz, 3H). 13 C NMR (151 MHz, CDCl 3 ): δ = 156.4, 154.2, 133.0, 129.2, 129.0, 128.9, 127.1, 123.7, 122.7, 119.6, 116.3, 111.0, 20.4, 13.1.…”

Recent Synthetic Applications of Catalyst-Free Photochemistry

“…In 2016, Li's group reported a clean and simple synthetic method to benzofurans, without any acid, base additive or transition-metal catalyst, instead promoted by light irradiation (Scheme 66). 129 This reaction was efficient and tolerated numerous functional groups. It was found that when the C3 substituent was switched from phenyl to alkyl, the reaction rate decreased tremendously.…”