Construction of a CF₃-Containing Benzofurofuranone Skeleton from Coumarins via Reductive Coupling and Acid-Mediated Ring Contraction

Abstract

Magnesium-promoted reductive introduction of a trifluoroacetyl group to coumarin in the presence of ethyl trifluoroacetate and the subsequent treatment with trifluoroacetic acid led to simple access to a trifluoromethylated benzofurofuranone at 8a-position with a high regio-and stereoselectivity. Trifluoromethylated or difluoromethylated benzofurofuranone derivatives were also prepared from coumarins including naturally occurring ones only in two successive steps, which might have potential bioactivity in medicinal chemistry.

A Simple Protocol from Benzalacetones to 1,1,1‐Trifluoro‐2,5‐diketones and 2‐(Trifluoromethyl)furans by Reductive Trifluoroacetylation

“…Consequently, a tentative reaction mechanism was proposed on the basis of above results as well as our previous investigation (Scheme ) , . At first, an intermediate A is formed by a single electron transfer from magnesium to trans ‐benzalacetone 1a .…”

“…As another direct formation of 2‐(trifluoromethyl)furans, Xu and co‐workers reported an elegant time‐economical approach to synthesize trifluoromethylated furans from conjugated keto esters and trifluoroacetic anhydride (Scheme b) . We reported a variety of synthesis of fluorinated organic compounds by use of ethyl trifluoroacetate as a fluorinated reagent through magnesium‐promoted reduction of aromatic conjugated system . In our recent research, we disclosed a useful two‐step protocol to synthesize 4‐(trifluoromethyl)cyclopentenones and 2‐(trifluoromethyl)furans through reductive trifluoroacetylation of aromatic ynones and subsequent cyclization …”

Regioselective Silylations of Propargyl and Allyl Pivalates through Ca-Promoted Reductive C(sp3)–O Bond Cleavage

“…In the previous research, reductive coupling reactions involving metals or metal salts, such as magnesium, sodium, and samarium iodide, have been well-documented by many groups, including ours. However, despite its vast abundance in the Earth’s crust, eco-friendliness, and commercial availability, the use of calcium in organic processes has been limited to a few areas, including calcium-catalyzed transformations, heavy Grignard reagents, and simple Birch-type reductions in liquid ammonia .…”

[3 + 2] Coupling of Quinone Monoacetals with Vinyl Ethers Effected by Tetrabutylammonium Triflate: Regiocontrolled Synthesis of 2-Oxygenated Dihydrobenzofurans

“…Attracted by the importance of this skeleton, various groups have reported the construction methods of it by several approaches. − However, many cases require the stepwise approach from readily available starting materials. − In contrast, the coupling of phenols with vinyl ethers can simultaneously form C–C and C–O bonds in one step . Especially, the recent advancement of palladium-catalyzed reactions and concomitant ligand chemistry enabled the stereoselective synthesis of 2-oxygenated dihydrobenzofurans (Scheme a). , These methods require ortho -halogenated phenols as the starting materials and specific expensive ligands.…”