An efficient and practical copper‐catalyzed domino synthesis of benzo[4,5]imidazo[1,2‐a]pyrimidin‐4(10H)‐ones has been developed. The protocol uses N‐(2‐halophenyl)‐3‐alkylpropiolamides and cyanamide as the starting materials, inexpensive copper(I) iodide and pipecolinic acid as the catalyst and ligand, and the corresponding products were obtained in moderate to good yields.
Meldrum’s acid has turned out to be a useful ketene equivalent when faced to nitrone dipoles to form various isoxazolidin‐5‐one derivatives under very mild Brønsted base organocatalytic conditions. The first asymmetric version of this original domino anionic formal [3+2] cycloaddition–decarboxylation reaction was demonstrated by means of quinine‐based organocatalysts.
A four‐electron electrocyclic ring‐opening/intermolecular [4+2] cycloaddition of α‐hydroxycyclobutenones is reported. The reaction represents the first example for the intermolecular cycloaddition of the extensively studied enol‐ketene intermediate, and provides a new synthetic route to multiply substituted δ‐lactams in high stereoselectivity.
An efficient copper‐catalyzed α‐aminoxylation of ketones with 2,2,6,6‐tetramethylpiperidine‐1‐oxyl (TEMPO) is presented for the synthesis of 2‐aryloxy‐1‐aryl‐2‐(2,2,6,6‐tetramethylpiperidin‐1‐yloxy)ethanones in moderate to excellent yields. It is noteworthy that the copper/iron (Cu/Fe) catalyst can be recovered and reused several times with high catalytic reactivity.
An efficient synthetic strategy for the unique class of pyrazolo[1,2‐a]cinnolines was developed through a rhodium‐catalyzed oxidative coupling of N‐aryl‐1H‐pyrazol‐5(4H)‐ones with internal alkynes. This protocol features use of the pyrazolone function in the substrate as an intrinsic directing group, hexafluoroisopropyl alcohol (HFIP) as the solvent, and mild reaction conditions as well as a wide substrate scope.
The iron(III) chloride‐multicatalyzed dioxygenation of enamides with TEMPO in the presence of alcohols has been developed. This multicomponent domino process affords efficient new strategies for the synthesis of α‐oxy‐N‐acylhemiaminals or α‐oxyimides in good to excellent yields under mild conditions.
In the presence of sodium carbonate, the [4+3] cycloadditions of α‐halogeno hydrazones with nitrones were performed efficiently, and affording 2,3,4,7‐tetrahydro‐1,2,4,5‐oxatriazepines in moderate to high yields.
For the synthesis of multisubstituted dispirocyclohexane derivatives, a Rauhut–Currier‐initiated organocascade reaction between 2‐arylideneindan‐1,3‐diones and activated alkenes in the presence of diazabicyclo[2.2.2]octane (DABCO) was demonstrated. The functionalized dispirocyclohexanes with a wide range of substituents were obtained in satisfactory to excellent chemical yields (58–99%) with high chemo‐ and diastereoselectivities (>95:5 dr). This organocatalytic reaction proceeded smoothly through Michael/Michael cyclization, which involves the formation of three new carbon‐carbon bonds with simultaneous construction of two all‐carbon spiro quaternary centers.
Herein a practical and efficient protocol for preparing a range of aminoisoquinolines is reported. Various aminoisoquinolines were prepared in moderate to good yields from the corresponding 2‐methylbenzonitriles and benzonitriles upon treatment with potassium tert‐butoxide.
A sequential one‐pot synthesis of Michael adducts of aroylmethylidenemalonates with activated aromatics is described. The method involves treatment of trans‐2‐aryl‐3‐nitro‐cyclopropane‐1,1‐dicarboxylates with boron trifluoride etherate to form aroylmethylidenemalonates in situ and then addition of activated aromatics such as indoles, carbazole, pyrrole, thiophenes, methoxybenzenes and benzodioxole followed by a catalytic amount of indium(III) triflate to the same reaction vessel. To prove the synthetic potential of the resulting Michael adducts, one of the adducts was transformed into a pharmaceutically interesting dihydropyridazinone derivative.
The palladium‐catalyzed, one‐pot arylative cyclization of 3‐(γ,δ‐disubstituted)allylidene‐2‐oxindoles afforded spirodihydronaphthalene‐2‐oxindole frameworks via an oxidative Heck arylation (Fujiwara–Moritani reaction), an allylic palladium migration, and an aryl C H bond functionalization/arylation cascade of reactions. This is a first example of the palladium‐catalyzed oxidative arylation and an aryl C H bond functionalization/arylation cascade reaction which involves an electrophilic arylative quenching of a π‐allylpalladium intermediate and a regio‐controlled aryl C H bond activation assisted by a weak palladium‐arene interaction.
Zinc‐catalyzed 1,4‐oxofluorinations of 3‐en‐1‐ynamides with Selectfluor in acetonitrile/water proceeded with high regio‐ and stereoselectivity, giving E‐configured γ‐fluoro‐α,β‐unsaturated amides efficiently. Our control experiments indicate that kinetically unstable C‐bound zinc dienolates are chemically reactive to undergo SE2′‐electrophilic fluorinations whereas the detectable O‐bound dienolates preferably undergo protodemetalation reactions instead.
An efficient route to 4‐cyanoquinolines via a palladium‐catalyzed cyanative reaction of 2‐alkynylbenzaldimines with isocyanides has been developed. The transformation proceeds through 6‐endo cyclization, isocyanide insertion, and cyanation. 4‐Amidylisoquinolines can be generated as well if water is involved in the reaction.
The regioselectivity of the [3+2] cyclocondensation of trifluoromethyl‐α,β‐ynones with hydrazines can be readily tuned to preferentially afford either 3‐ or 5‐trifluoromethylpyrazoles through variation of the reaction conditions. Under catalysis with copper(II) acetate (2.0 mol%), cyclocondensation proceeded smoothly to yield 3‐trifluoromethylpyrazoles with high regioselectivity. In contrast, when the reaction was conducted in dimethyl sulfoxide under catalyst‐free conditions, the formation of 5‐trifluoromethylpyrazoles was predominantly observed.
A synthetic strategy has been developed for the synthesis of 2‐dialkylaminoquinolines from easily available quinoline N‐oxides, tertiary amines, diisopropyl H‐phosphonate and carbon tetrachloride (CCl4) in one pot under metal‐free conditions at room temperature.
The complex [Ir(cod)Cl]2/DPPF or rac‐BINAP is an efficient catalyst for the [2+2+2] cycloaddition of α,ω‐diynes with cyanamides. A wide range of cyanamides derived from secondary amines are good coupling partners for α,ω‐diynes. The reaction of unsymmetrical α,ω‐diynes possessing two different internal alkyne moieties with cyanamides is regioselective. A competitive experiment showed that cyanamide is more reactive than nitrile. This higher reactivity of cyanamide than nitrile was analyzed based on density functional theory (DFT) calculations at the B3LYP level.
A convenient gold‐catalyzed strategy for the synthesis of imidazo[1,2‐a]pyridine derivatives has been developed via gold carbene complexes. This transformation opens a new synthetic route to a variety of 3‐carbonyl‐substituted imidazo[1,2‐a]pyridines using air as oxidant affording the products in good yields.
