CsF-Mediated Reaction of Trifluorodiazoethane with 3-Nitroindoles Enables Access to Trifluoromethylpyrazolo[4,3-b]indoles.

A mild and metal-free strategy for the construction of trifluoromethylated pyrazolo[4,3-b]indoles through the reaction of N-substituted 3-nitroindoles with trifluorodiazoethane is reported. This operationally simple transformation involves a [3 + 2] cycloaddition of trifluorodiazoethane with 3-nitroindole, followed by the elimination of the nitro group to furnish pyrazole-fused indoles. The synthetic utility of this method is further demonstrated by applying it to other heterocycles, such as 3-nitrobenzothiophene and 2-nitrobenzofuran.

Substrate-controlled product divergence in the reaction of α-fluoro-ß-ketoamides with arynes.

An interesting substrate-controlled reactivity switch has been observed in the reaction of α-fluoro-ß-ketoamides with arynes. The reaction of secondary α-fluoro-ß-ketoamides with arynes provided access to α-aryl-α-fluoroacetamides through an arylation/deacylation sequence. Interestingly, the reaction of tertiary α-fluoro-ß-ketoamides resulted in the C-C σ-bond insertion reaction to afford 1,2-disubstituted arenes.

Organocatalytic asymmetric nitroso aldol reaction of α-substituted malonamates.

A practical enantioselective N-selective nitroso aldol reaction of α-methylmalonamates with a nitrosoarene is reported. The reaction employs the Takemoto thiourea catalyst for the induction of enantioselectivity, and the corresponding optically active oxyaminated malonamates were obtained in reasonably good yields.

Base-Mediated Intramolecular Cyclization of α-Nitroethylallenic Esters as a Synthetic Route to 5-Hydroxy-3-pyrrolin-2-ones.

An unprecedented Cs2CO3-mediated intramolecular cyclization/rearrangement cascade that transforms α-nitroethylallenic esters to functionalized pyrrolin-2-ones has been uncovered. This reaction provides a new and practical approach for the synthesis of medicinally privileged 5-hydroxy-3-pyrrolin-2-ones under mild conditions. The broad potential of this new method was demonstrated by an efficient Au/Ag-catalyzed heteroarylation of 5-hydroxy-3-pyrrolin-2-ones employing electron-rich heteroarenes to furnish heteroaryl-lactam derivatives.

Utilization of Unsymmetric Diaryliodonium Salts in α-Arylation of α-Fluoroacetoacetamides.

The use of unsymmetric diaryliodonium salts as a versatile class of arylating agents has been demonstrated by developing a novel strategy to quickly access α-arylated α-fluoroacetoacetamides. The protocol provides a convenient metal-free method for the α-arylation of a diverse class of fluorinated acetoacetamides, and the products are obtained in good yields. The strategy, upon use of electron-deficient diaryliodonium salts as an arylating agent, provides α-fluoroacetamides through a spontaneous arylation/deacylation cascade.

The Bestmann-Ohira Reagent and Related Diazo Compounds for the Synthesis of Azaheterocycles.

Azaheterocycles are one of the most prevalent classes of compounds present in numerous bioactive compounds, natural products, and agrochemicals, and undoubtedly, new methods to access them are always in high demand. Among the methods available, the 1,3-dipolar cycloaddition reactions involving diazo compounds are particularly attractive because of their ability to rapidly construct densely functionalized azaheterocycles in a regioselective manner. In this context, the Bestmann-Ohira reagent has become a well-known reagent for the 1,3-dipolar cycloaddition reactions to produce phosphonylated heterocycles, besides its widespread use as a homologating agent for the conversion of aldehydes to alkynes. This account details our efforts toward broadening the synthetic utility of the Bestmann-Ohira reagent and related compounds for the preparation of azaheterocycles such as pyrazoles, spirooxindoles, triazoles, triazolines, and spiropyrazolines, emphasizing on domino multicomponent reactions employing readily available feedstock reagents.

Substrate-controlled, PBu3-catalyzed annulation of phenacylmalononitriles with allenoates enables tunable access to cyclopentenes.

Divergence in the PBu3-catalyzed [3+2] annulation of phenacylmalononitriles with allenoates, controlled by the γ-substitution on allenoates, offers a tunable synthesis of multifunctionalized cyclopentene carboxamides and cyclopentenols. An unprecedented formation of cyclopentene carboxamide was observed when allenic esters bearing a substitution at the γ-position were employed, while unsubstituted allenoates produced cyclopentenols. The former reaction likely involves a Michael/aldol/nucleophilic cyclization sequence in a domino manner.

Base-mediated 1,6-conjugate addition of the Seyferth-Gilbert reagent to para-quinone methides.

A 1,6-conjugate addition reaction of the Seyferth-Gilbert reagent (SGR) to p-quinone methides is reported. This base-mediated protocol allows rapid access to diarylmethylated diazomethylphosphonates. The reaction proceeds under mild basic conditions, making it a practical approach for the synthesis of diarylmethylated diazomethylphosphonates with a broad substrate scope. Interestingly, the treatment of the conjugate adduct with a catalytic amount of rhodium acetate resulted in the 1,2-aryl migration of the rhodium carbenoid intermediate to generate the corresponding 1,2-diaryl alkenylphosphonates in excellent yields.

Fluoride-Mediated α-Selective 1,6-Conjugate Addition of Allenic Esters to p-Quinone Methides.

An efficient and expedient fluoride-mediated α-selective 1,6-conjugate addition of allenic esters to para-quinone methides has been developed. The reaction exhibited an excellent substrate scope, and a wide range of α-diarylmethylated allenic esters were obtained in good to excellent yields. It was further shown that the strategy could be extended to isatin-derived quinone methides yielding allenic esters containing 3,3-disubstituted oxindoles. The tert-butyl ester of α-diarylmethylated allenoate was effectively converted into γ-butenolide through a Au/Ag catalyzed cyclization strategy.

Rapid and selective synthesis of spiropyrazolines and pyrazolylphthalides employing Seyferth-Gilbert reagent.

An unexpected product-selectivity in the reaction of 2-arylideneindane-1,3-dione with dimethyl diazomethylphosphonate leading to the formation of two different types of products is reported. The reaction carried out in acetone in the presence of catalytic amount of cesium fluoride afforded spiropyrazoline phosphonates via 1,3-dipolar cycloaddition reaction, whereas the reaction in methanol yielded an interesting class of pyrazolylphthalides. This strategy provides an efficient alternative method for the construction of pyrazolylphthalides, and moreover, the process is general, works under mild conditions, and exhibits high functional group compatibility.