Electrochemical Reductive Bimolecular Cycloaddition of 2-Arylideneindane-1,3-diones for the Synthesis of Spirocyclopentanole Indane-1,3-diones.

An electrochemical reductive bimolecular cycloaddition of 2-arylideneindane-1,3-diones has been reported for the synthesis of spirocyclopentanole indane-1,3-diones bearing five contiguous stereocenters with vicinal tetrasubstituted stereocenters, especially involving a quaternary carbon center, in moderate to good yields and excellent diastereoselectivities. The present protocol features mild reaction conditions, no external chemical redox reagents, excellent atom economy, and gram-scale synthesis. In addition, a mechanistic investigation indicates that the reactions proceed through a radical pathway.

Synthesis of 2,4,6-Trisubstituted Pyrimidines through Copper-Catalyzed [4 + 2] Annulation of α,β-Unsaturated Ketoximes with Activated Nitriles.

The copper-catalyzed [4 + 2] annulation of α,β-unsaturated ketoximes with activated nitriles for the rapid construction of 2,4,6-trisubstituted pyrimidines in moderate to good yields has been developed. The reaction features synthetic simplicity, good functional group tolerance, and gram-scale applicability. A plausible mechanism is proposed based on mechanistic investigations.

Copper-catalyzed three-component annulation toward pyrroles the cleavage of two C-C bonds in 1,3-dicarbonyls.

The first copper-catalyzed three-component annulation of α,β-unsaturated ketoximes, 1,3-dicarbonyls and paraformaldehyde has been documented. This novel strategy achieved the two C-C bond cleavage of 1,3-dicarbonyl compounds directly as a single-carbon synthon and provided a new and highly efficient method for the synthesis of 2,3-disubstituted pyrroles in moderate to good yields with broad functional group compatibility.

Copper-catalyzed [4+2] oxidative annulation of α,β-unsaturated ketoxime acetates with ethyl trifluoropyruvate.

A novel route for tandem C-N/C-O formation copper-catalyzed [4+2] oxidative annulation of α,β-unsaturated ketoxime acetates with ethyl trifluoropyruvate to synthesize valuable trifluoromethyl-containing 2-1,3-oxazines in moderate to good yields is developed. This procedure represents the first [4+2] oxidative annulation of oxime derivatives with activated CO bonds and provides an alternative route towards functionalized 2-1,3-oxazines.

-Difluoromethylation of -pyridyl-substituted anilines with ethyl bromodifluoroacetate.

A general protocol for -difluoromethylation of aniline derivatives is developed. Commercially available ethyl bromodifluoroacetate serves as a difluorocarbene source in the presence of a base. This carbene surrogate is attractive owing to its favorable stability, environmental friendliness and inexpensiveness.

Copper-Catalyzed Three-Component Cascade Annulation for Divergent Syntheses of Imidazoles and Dihydroimidazoles.

The first example of divergent -heterocycle syntheses through a copper-catalyzed three-component reaction of ,-unsaturated ketoximes, paraformaldehyde, and amines has been documented. In particular, this divergent synthetic strategy was achieved by controlling the reaction conditions to afford the corresponding imidazoles and dihydroimidazoles in moderate to good yields with a broad substrate scope and good functional group compatibility.

The copper-catalyzed synthesis of dihydrooxazoles from α,β-unsaturated ketoximes and activated ketones.

The first copper-catalyzed [3+2]-type condensation reaction of α,β-unsaturated ketoximes with activated ketones has been described for the synthesis of dihydrooxazoles, especially trifluoromethyl-decorated dihydrooxazoles. Notable features of this method include its broad substrate scope, good functional group tolerance, and simple operation.

Copper-catalyzed regioselective [3+2] annulation of malonate-tethered acyl oximes with isatins.

A copper-catalyzed regioselective [3+2] annulation of malonate-tethered acyl oximes with isatins was developed, affording valuable 2,3-dihydrooxazole-spirooxindoles in moderate to good yields with excellent diastereoselectivity. The reaction sequence involves Cu(i) initiated N-O bond cleavage, 1,5-HAT and C-N bond formation. The protocol features mild reaction conditions and broad substrate scope.

The copper(ii)-catalyzed and oxidant-promoted regioselective C-2 difluoromethylation of indoles and pyrroles.

A novel and efficient approach for the highly selective C-2 difluoromethylation of indole derivatives was developed by using sodium difluoromethylsulfinate (HCFSONa) as the source of difluoromethyl groups and a Cu(ii) complex as the catalyst. Various substrates were well tolerated in this transformation and the desired products were obtained in moderate to good yields. Moreover, the late-stage C-2 difluoromethylation of bioactive molecules containing an indole ring was achieved in good yields.

NHI-Triggered [4 + 2] Annulation of α,β-Unsaturated Ketoxime Acetates with -Acetyl Enamides for the Synthesis of Pyridines.

The NHI-triggered formal [4 + 2] annulation of α,β-unsaturated ketoxime acetates with -acetyl enamides has been developed. The current protocol employs electron-rich enamides as C2 synthons and enables the efficient and straightforward construction of polysubstituted pyridines in moderate to good yields based on metal-free systems. The reaction tolerates a wide range of functional groups and represents an alternate route toward the synthesis of pyridine derivatives.

Continuous Electrochemical Synthesis of Iso-Coumarin Derivatives from o-(1-Alkynyl) Benzoates under Metal- and Oxidant-Free.

A non-oxidant and metal-free strategy for synthesizing iso-coumarin by using a continuous electrochemical microreactor to initiate an oxidative cyclization reaction of o-(1-alkynyl) benzoate and radicals. This efficient and clean continuous electrosynthesis method not only avoids the complicated gas protection operation and production of by-products in the batch processes, but also help to overcome the difficulty that batch metal catalysis and electrocatalysis are difficult to scale up, and has the potential for pilot-scale experiment.

Copper-Catalyzed N-O Cleavage of α,β-Unsaturated Ketoxime Acetates toward Structurally Diverse Pyridines.

The copper-catalyzed [4 + 2] annulation of α,β-unsaturated ketoxime acetates with 1,3-dicarbonyl compounds for the synthesis of three classes of structurally diverse pyridines has been developed. This method employs 1,3-dicarbonyl compounds as C2 synthons and enables the synthesis of multifunctionalized pyridines with diverse electron-withdrawing groups in moderate to good yields. The mechanistic investigation suggests that the reactions proceed through an ionic pathway.

A Palladium-Catalyzed α-Arylation of Oxindoles with Aryl Tosylates.

A palladium-catalyzed monoselective C3 arylation of 2-oxindoles with aryl tosylates is described. With the Pd/CM-phos catalyst system, the corresponding 3-arylated oxindoles can be obtained in good to excellent yields (≤97%). The reaction conditions are mild (using 0.

Organocatalytic Asymmetric Benzylation and Aldol-Hemiacetalization of α,β-Unsaturated Trifluoromethyl Ketones: Efficient Enantioselective Construction of 3,4-Dihydroisocoumarins.

A new method has been developed for the organocatalytic enantioselective benzylation and aldol-hemiacetalization of α,β-unsaturated trifluoromethyl ketones with toluene derivatives in the presence of a tertiary amine-thiourea catalyst. This method represents a facile and efficient strategy for the asymmetric synthesis of optically active 3,4-dihydroisocoumarins bearing a trifluoromethylated tetrasubstituted carbon stereocenter with high enantioselectivity. Notably, this strategy was used to synthesize several chiral trifluoromethylated analogues of typharin with high efficiency.

A tertiary amine catalyzed carbocyclization sequence to furnish spirocyclo hexene systems having vicinal quaternary stereocenters.

Two types of enolates can be formed stepwise from enolisable 1,3-dicarbonyl-substituted propene systems in the presence of catalytic amounts of 1,4-diazabicyclo[2.2.2]octane (DABCO) to accomplish a highly selective carbocyclization with β,γ-unsaturated α-keto esters, giving functionalized spiroketones with vicinal quaternary stereocenters.