Iron-Facilitated Oxidative Radical Decarboxylative Cross-Coupling between α-Oxocarboxylic Acids and Acrylic Acids: An Approach to α,β-Unsaturated Carbonyls

Abstract

The first Fe-facilitated decarboxylative cross-coupling reaction between α-oxocarboxylic acids and acrylic acids in aqueous solution has been developed. This transformation is characterized by its wide substrate scope and good functional group compatibility utilizing inexpensive and easily accessible reagents, thus providing an efficient and expeditious approach to an important class of α,β-unsaturated carbonyls frequently found in bioactive compounds. The synthetic potential of the coupled products is also demonstrated in subsequent functionalization reactions. Preliminary mechanism studies suggest that a free radical pathway is involved in this process: the generation of an acyl radical from α-oxocarboxylic acid via the excision of carbon dioxide followed by the addition of an acyl radical to the α-position of the double bond in acrylic acid then delivers the α,β-unsaturated carbonyl adduct through the extrusion of another carbon dioxide.

Iron Catalyzed Oxidative Coupling, Addition, and Functionalization

“…Decarboxylation coupling reactions are amongt he most important tools to construct CÀCb onds as ar esulto ft heir high efficiency and excellent selectivity. [10][11][12] In 2009, an iron-catalyzed intermoleculard ecarboxylative coupling of proline derivatives with naphthols or indole was established, [11] whiche nabled the formation of C(sp 3 )À C(sp 2 )b onds to assemble tertiary aminonaphthols andt ertiary aminoindole (Scheme 13).…”

“…As shown in Scheme 14, iron-catalyzed decarboxylative coupling reactions of acrylic acids have been developed for the construction of variousC ÀCb onds. [12] Mao and co-workers [12a] have first employed ac ombination of ferrocene catalystw ith DTBP oxidantt ot rigger decarboxylation of an acrylic acid followed by oxidative coupling with abenzyl C(sp 3 )ÀHbond leading to the formation of aC (sp 3 )ÀC(sp 2 )b ond (Scheme 14 a).…”

“…According to the resultsd escribed above, iron-catalyzed oxidative coupling, addition, and functionalization for constructing the CÀCbond mainlyrely on three cases:iron catalysts, oxidants,r eactivity of substrates. [1][2][3][4][5][6][7][8][9][10][11][12][13][14][15][16][17] The majority of these transformationsr equires ubstrates with an electron-rich heteroatom to activate the relatedC ÀHb onds, which sequentially undergo the cleavage to generate the stable carbon-centered radicals. For the intermoleculard ifunctionalization of alkenes, more stable carbon-centered radicals are needed, which were reported to be formed from the cleavage of the CÀNb onds [15] or the CÀHb onds adjacent to two electron-rich sulfur atoms.…”

Divergent Synthesis and Evaluation of the in vitro Cytotoxicity Profiles of 3,4‐Ethylenedioxythiophenyl‐2‐propen‐1‐one Analogues

“…In recent decades, diaryl 2‐propenones have been investigated for their biological activities, including as antimalarial, antibacterial, antitumor, antioxidant, antihyperglycemic, and anti‐HIV agents . Recently, Guo and co‐workers developed an efficient synthesis of α,β‐unsaturated carbonyl compounds by Fe II ‐mediated decarboxylative cross‐coupling reactions, whereas Correa et al. established the synthesis of the γ‐butenolide natural product framework with epoxidation of 2‐propenone as a crucial step .…”

“…[2] In recent decades, diaryl 2-propenones have been investigated for their biological activities, including as antimalarial, [3] antibacterial, [4] antitumor, [5] antioxidant, [6] antihyperglycemic, [7] and anti-HIV agents. [8] Recently,G uo and co-workers developed an efficient synthesis of a,b-unsaturated carbonyl compounds by Fe II -mediated de-carboxylative cross-couplingr eactions, [9] whereas Correa et al established the synthesis of the g-butenolide natural product framework with epoxidation of 2-propenone as ac rucial step. [10] Owingt ot heir biological importance,n itrogen-containing six-membered pyrimidines [11] and five-membered isoxazoles were synthesized fromc halcones by cyclocondensation reactions.…”