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 novel synthetic method to access fused indolin‐3‐ones with a tetrasubstituted carbon stereocenter has been developed via NHC‐catalyzed umpolung formal [3+3] cycloaddtion of enals with isatogens. This methodology could be also applied for the quick construction of the 6‐5‐5 tricyclic pyrrolo[1,2‐a]indole skeleton which is frequently found as a core structure of many indole alkaloids.
Potassium hydroxide‐catalyzed hydrosilylation exhibits excellent activity and chemoselectivity for the reduction of cyclic imides under mild reaction conditions. The chemoselectivity of the reduction system may be readily tuned by changing the identity and stoichiometry of the hydrosilanes: a polymethylhydrosiloxane (PMHS)/potassium hydroxide reduction system resulted in the reduction of various cyclic imides to the corresponding ω‐hydroxylactams in 70–94% yield, while the diphenylsilane (Ph2SiH2)/potassium hydroxide reduction system selectively afforded the aryl lactams in 33–95% yield. These catalytic protocols tolerate diverse functional groups and are easy to scale up.
The first successful gold(I)‐catalyzed reaction of aryl aldehydes with trimethyl(arylethynyl)silanes to furnish bis‐alkynylated derivatives is reported. Key C C bond‐forming events involved in the catalytic cycle are analyzed.
An efficient and concise one‐pot strategy for the direct alkylation of quinoline N‐oxides via palladium‐catalyzed dual C H bonds activation has been developed. This methodology provides quinoline‐containing heterocyclic molecules in moderate to excellent yields.
An efficient methodology for introducing a β‐alkoxy acrylate unit onto the indolic C‐2 position of 3‐substituted indoles has been realized by oxidative radical alkylation of indoles with a xanthate bearing dialkyl acetal functionality and subsequent elimination of alcohol by treatment with 1,8‐diazabicyclo[5.4.0]undec‐7‐ene (DBU). The indole‐dienes thus prepared are quite stable and can be stored at room temperature for several months without obvious deterioration. Next, the indole‐dienes were successfully applied in an asymmetric cascade reaction with propargyl aldehyde catalyzed by MacMillan’s imidazolidinone and trichloroacetic acid (TCA), affording tetracyclic spiroindolines or tricyclic hydrocarbazoles in good to excellent yields with excellent ees. The practicality of this cascade was demonstrated by a gram scale preparation of a tetracyclic spiroindoline product with as low as 1 mol% catalyst loading and further elaboration of this spiroindoline compound into valuable intermediates for alkaloid synthesis.
A general method to generate umpolung of aldimines with cyanide was developed via the addition of cyanide to aldimines followed by a proton transfer from the carbon atom to the nitrogen atom in the resulting cyanide adducts. This novel method was successfully applied to the first imino‐Stetter reaction of aldimines obtained from 2‐aminocinnamic acid derivatives and aromatic aldehydes with cyanide, affording 2‐aryl‐substituted indole‐3‐acetic acid derivatives. Furthermore, the usefulness of this method was successfully demonstrated by the synthesis of an FPTase inhibitor, one of the biologically important 2‐arylindole‐3‐acetic acid derivatives.
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.
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.
The first enantioselective Friedel–Crafts alkylation of indoles and pyrroles with 3‐hydroxy‐3‐indolyloxindoles to access two novel types of 3,3‐diaryloxindoles catalyzed by chiral imidodiphosphoric acids has been reported. A range of quaternary carbon centered 3,3‐diaryloxindoles were synthesized in high yield (up to >99%) with excellent enantioselectivity (up to 98% ee) at low catalyst loadings (as low as 0.5 mol%). The Friedel–Crafts reaction between indoles and 3‐hydroxy‐3‐indolyloxindoles is amenable to gram scale syntheses.
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.
A more practical and efficient catalytic asymmetric chlorolactonization of styrene‐type carboxylic acids with 1,3‐dichloro‐5,5‐dimethylhydantoin (DCDMH) using C3‐symmetric cinchonine‐squaramide (CSCS) as organocatalyst has been developed. A series of chiral chloro‐substituted isochroman‐1‐ones was obtained in excellent yields (up to 95%) and enantioselectivities (up to 99% ee), whwereby the results for chloro‐substituted isochroman‐1‐ones are the best ever achieved. The catalyst can be recovered and reused for six cycles. Moreover, the chlorolactonization product 3b was further transformed to optically active bicyclic isochroman‐1‐one derivatives in high yield without losing the enantioselectivity. Furthermore, compounds 3e and 2n proved to be highly potent inhibitors of the HIV‐1 in TZM‐bl cells.
The synthesis of chiral bidentate bisphosphonite ligands based on the TADDOL motif from readily available starting materials has been developed. Taking advantage of the modular nature of the building blocks, a diverse ligand library has been prepared. Their catalytic potential has been evaluated in the asymmetric hydroformylation of styrene and derivatives. These catalysts showed high activity and provided the aldehydes in high enantiomeric purity.
A three‐component reaction involving isocyanides, o‐alkynyltrifluoroacetanilides, and amines for the efficient synthesis of 2‐substituted 1H‐indole‐3‐carboxamidines has been developed. The reaction proceeds through intramolecular aminopalladation of alkynes activated by isocyanide‐ligated palladium(II) species. Dioxygen acts as the sole oxidant to regenerate the active palladium(II) species.
A new one‐pot palladium‐catalyzed process between N‐tosylhydrazones, N‐(dihalophenyl)‐imidates, and amines was designed. This reaction involves Barluenga cross‐coupling and N‐arylation followed by cyclization to produce functionalized benzimidazoles. During this transformation, one C C bond and two C N bonds were created by a single palladium‐catalyzed reaction. Depending on the starting materials, a library of 5‐(1‐arylvinyl)‐1H‐benzimidazoles was synthesized. Among several arylvinylbenzimidazole derivatives evaluated, one compound exhibits excellent antiproliferative activity in the nanomolar concentration range against human colon carcinoma cell lines (HCT‐116) and human lung adenocarcinoma epithelial cell lines (A549).
The asymmetric aldol reaction of 3‐acetyl‐2H‐chromen‐2‐ones and isatins has been realized by using a bifunctional quinidine‐derived urea as the catalyst. The corresponding 3‐hydroxyoxindole derivatives containing a 2H‐chromen‐2‐one moiety were obtained in good yields and high enantioselectivities. When (Z)‐ethyl 2‐benzylideneacetoacetate was used as the substrate, a mixture of two diastereomers (both Z and E) was obtained due to isomerization of the double bond under the reaction conditions.
