Indolo[3,2-c]quinolones have been efficiently synthesized via an acid-mediated, one-pot, three-component condensation of arylhydrazines, o-aminoacetophenones, and triazines or nitriles. The synthetic application of this method is showcased by the concise synthesis of isocryptolepine alkaloid and a series of its synthetic analogues with demonstrated cancer cell antiproliferative activities.

Indolo[3,2-c]quinolones have been efficiently synthesized via an acid-mediated, one-pot, three-component condensation of arylhydrazines, o-aminoacetophenones, and triazines or nitriles. The synthetic application of this method is showcased by the concise synthesis of isocryptolepine alkaloid and a series of its synthetic analogues with demonstrated cancer cell antiproliferative activities.

A highly efficient synthetic method for expeditious and selective assembly of tetraazopyrenes (TAPy) is reported, based on the novel reaction of electrophilically activated nitroalkanes with aromatic amines. Remarkably, the nitroalkanes play a dual role in this process, also serving as mild and efficient oxidants promoting aromatization of the final product and allowing for the exclusion of a poorly controllable aerobic treatment.

The alkali metal-templated addition of aryloxides across the double bond of non-conjugated cyclopropenes is described. High cis-selectivity is achieved through a directing effect of a strategically positioned carboxamide functionality.

An efficient approach toward enantioenriched eight-membered heterocycles via the intramolecular formal substitution of bromocyclopropanes with oxygen-based nucleophiles has been developed. The reaction proceeds via a reactive cyclopropene intermediate, which undergoes a rapid 8-endo-trig cyclization affording cis-fused [6.1.0] bicyclic products exclusively. The quaternary chiral center in the cyclopropene governs the configuration of the other two stereocenters in the final product.

A novel method for the assembly of medium heterocycles via an intramolecular nucleophilic addition to cyclopropenes generated in situ from the corresponding bromocyclopropanes is described. The exo-trig nucleophilic cyclizations were shown to proceed very efficiently and in a highly diastereoselective fashion affording cis-fused bicyclic products possessing 7 to 10-membered medium rings; starting from a diastereomeric mixtures of bromocyclopropanes.

An expeditious and cost-efficient method for synthesis of 1-arylcycloprop-2-ene-1-carboxamides was developed. This one-pot protocol involving coupling of amines with acyl chlorides, generated upon treatment of cyclopenylcarboxylic acids with oxalyl chloride, is applicable for the preparation of sensitive products with a reactive, unsubstituted strained double bond.

PPA-induced umpolung triggers efficient nucleophilic addition of unactivated anilines to nitroalkanes to produce N-hydroxyimidamides. The latter undergo sequential acid-promoted cyclocondensation with ortho-OH or ortho-NHR moieties to afford benzoxazoles and benzimidazoles, respectively.

A one-pot synthesis of various GABA amides has been demostrated, employing the nucleophilic addition of primary and secondary amines across the double bond of cyclopropene-3-carboxamides, followed by ring-opening of the resulting donor–acceptor cyclopropanes and subsequent in situ reduction of enamine (imine) intermediates.

PPA-activated nitroalkanes are employed in the design of a one-pot cascade transformation involving metal-free and oxidant-free direct ortho-C–H functionalization, followed by Beckman rearrangement and intramolecular cyclocondensation to produce benzoxazoles and benzobisoxazoles directly from easily available phenols.

Nitroalkenes were used as synthetic equivalents of the cyanomethylium cation in a modular, one-pot synthesis of 2-(3-indolyl)acetonitriles and 2,2-diarylacetonitriles involving electrophilic functionalization of aromatic and heteroaromatic C–H bond.

Synthesis of symmetric diarylamines via a twofold intermolecular electrophilic C–H functionalization of electron-rich arenes by umpolung-activated nitroalkane in polyphosphoric acid is demonstrated.

An efficient [4 + 4] cyclodimerization of cyclopropenemethanols operating via a two-fold strain release-driven addition of alkoxides across the double bond of cyclopropenes was investigated. This chemo- and diastereoselective transformation provided previously unknown 2,7-dioxatricyclo[7.1.0.04,6]decane scaffolds.

A new synthetic protocol for the preparation of 3-aryl-3-methoxycarbonyl cyclopropenes with an unsubstituted double bond has been developed that allowed for expanded substrate scope and improved product yields. The method involves Rh(II)-catalyzed transfer of carbenoids generated from unpurified aryldiazoesters, followed by desilylation, and is compatible with a wide range of aryldiazoesters. The employed continuous extraction of hardly soluble crude diazoesters helps avoid laborious and often cost-prohibitive isolation and purification of sensitive diazoester precursors.

A modular approach to 3-substituted 2-quinolones via a cascade annulation reaction between 4-nitroketones and hydrazines has been developed.

A general and efficient method for the preparative resolution of α- and β-bromocyclopropylcarboxylic acids has been developed. This protocol involves a sequence of two crystallizations with pseudo-enantiomeric amines, cinchonine, and cinchonidine, which yield both enantiomers of the acid in highly enriched form. Both alkaloids can be easily recovered and reused multiple times without any loss of efficacy.(1S,2R)-1-Bromo-2-methyl-2-phenylcyclopropane-1-carboxylic acidC11H11BrO2[α]D25 = +56.5 (c 0.22, CH2Cl2)Source of chirality: cinchonineAbsolute configuration: (1S,2R)(1S,2R)-1-Bromo-2-methyl-2-(p-tolyl)cyclopropane-1-carboxylic acidC12H13BrO2[α]D25 = +66.0 (c 0.11, CH2Cl2)Source of chirality: cinchonineAbsolute configuration: (1S,2R)(1S,2R)-1-Bromo-2-ethyl-2-phenylcyclopropane-1-carboxylic acidC12H13BrO2[α]D25 = +69.5 (c 0.12, CH2Cl2)Source of chirality: cinchonineAbsolute configuration: (1S,2R)(1S,2R)-1-Bromo-2-methyl-2-(naphthalen-2-yl)cyclopropane-1-carboxylic acidC15H13BrO2[α]D25 = +108.2 (c 0.12, CH2Cl2)Source of chirality: cinchonineAbsolute configuration: (1S,2R)(1S,2R)-1-Bromo-2-phenylcyclopropane-1-carboxylic acidC10H9BrO2[α]D25 = +166.0 (c 0.11, CH2Cl2)Source of chirality: cinchonineAbsolute configuration: (1S,2R)(1S,2R)-1-Bromo-2-methyl-2-(m-tolyl)cyclopropane-1-carboxylic acidC12H13BrO2[α]D25 = +77.5 (c 0.10, CH2Cl2)Source of chirality: cinchonineAbsolute configuration: (1S,2R)(1S,2R)-1-Bromo-2-(3,4-dimethylphenyl)-2-methylcyclopropane-1-carboxylic acidC13H15BrO2[α]D25 = +54.7 (c 0.17, CH2Cl2)Source of chirality: cinchonineAbsolute configuration: (1S,2R)(1S,2R)-1-Bromo-2-(4-ethylphenyl)-2-methylcyclopropane-1-carboxylic acidC13H15BrO2[α]D25 = +69.8 (c 0.12, CH2Cl2)Source of chirality: cinchonineAbsolute configuration: (1S,2R)(S)-1-Bromo-2,2-diphenylcyclopropane-1-carboxylic acidC16H13BrO2[α]D25 = +110.3 (c 0.20, CH2Cl2)Source of chirality: cinchonineAbsolute configuration: (S)(1S,2R)-1-Bromo-N,N-diethyl-2-methyl-2-phenylcyclopropane-1-carboxamideC15H20BrNO[α]D25 = +17.0 (c 0.19, CH2Cl2)Source of chirality: cinchonineAbsolute configuration: (1S,2R)Methyl (1S,2R)-1-bromo-2-methyl-2-phenylcyclopropane-1-carboxylateC12H13BrO2[α]D25 = +34.6 (c 0.22, CH2Cl2)Source of chirality: cinchonineAbsolute configuration: (1S,2R)Methyl (1S,2R)-1-bromo-2-methyl-2-(p-tolyl)cyclopropane-1-carboxylateC13H15BrO2[α]D25 = +42.6 (c 0.62, CH2Cl2)Source of chirality: cinchonineAbsolute configuration: (1S,2R)Methyl (1R,2S)-1-bromo-2-ethyl-2-phenylcyclopropane-1-carboxylateC13H15BrO2[α]D25 = −30.9 (c 0.80, CH2Cl2)Source of chirality: cinchonidineAbsolute configuration: (1R,2S)Methyl (1S,2R)-1-bromo-2-methyl-2-(naphthalen-2-yl)cyclopropane-1-carboxylateC16H15BrO2[α]D25 = +90.0 (c 0.60, CH2Cl2)Source of chirality: cinchonineAbsolute configuration: (1S,2R)Methyl (1S,2R)-1-bromo-2-phenylcyclopropane-1-carboxylateC11H11BrO2[α]D25 = +122.4 (c 0.84, CH2Cl2)Source of chirality: cinchonineAbsolute configuration: (1S,2R)Methyl (1R,2S)-1-bromo-2-methyl-2-(m-tolyl)cyclopropane-1-carboxylateC13H15BrO2[α]D25 = −30.2 (c 0.42, CH2Cl2)Source of chirality: cinchonidineAbsolute configuration: (1R,2S)Methyl (1S,2R)-1-bromo-2-(3,4-dimethylphenyl)-2-methylcyclopropane-1-carboxylateC14H17BrO2[α]D25 = +35.4 (c 0.82, CH2Cl2)Source of chirality: cinchonineAbsolute configuration: (1S,2R)Methyl (S)-1-bromo-2,2-diphenylcyclopropane-1-carboxylateC17H15BrO2[α]D25 = +85.6 (c 0.82, CH2Cl2)Source of chirality: cinchonineAbsolute configuration: (S)(S)-2,2-Dibromo-1-methylcyclopropane-1-carboxylic acidC5H6Br2O2[α]D25 = +49.3 (c 0.13, CH2Cl2)Source of chirality: cinchonidineAbsolute configuration: (S)Methyl (R)-2,2-dibromo-1-methylcyclopropane-1-carboxylateC6H8Br2O2[α]D25 = −62.0 (c 0.51, CH2Cl2)Source of chirality: cinchonineAbsolute configuration: (R)

3-Substituted 2-quinolones are obtained via a novel, metal-free transannulation reaction of 2-substituted indoles with 2-nitroalkenes in polyphosphoric acid. The reaction can be used in conjunction with the Fisher indole synthesis offering a practical three-component heteroannulation methodology to produce 2-quinolones from arylhydrazines, 2-nitroalkenes and acetophenone.

Densely substituted cyclopropanol and cyclopropylazole derivatives with three stereogenic carbons in the small cycle are obtained via a highly diastereoselective formal nucleophilic substitution of bromocyclopropanes. The chiral center at C-2 in bromocyclopropane dictates the configuration of the other two stereocenters that are successively installed via a sterically controlled addition of a nucleophile, followed by a thermodynamically driven epimerization of the resulting enolate intermediate.

A highly chemo- and diastereoselective protocol toward amino-substituted donor–acceptor cyclopropanes via the formal nucleophilic displacement in bromocyclopropanes is described. A wide range of N-nucleophiles, including carboxamides, sulfonamides, azoles, and anilines, can be efficiently employed in this transformation, providing expeditious access to stereochemically defined and densely functionalized cyclopropylamine derivatives.

A highly diastereoselective protocol for the formal nucleophilic substitution of 2-bromocyclopropylcarboxamides with azoles is described. A wide range of azoles, including pyrroles, indoles, benzimidazoles, pyrazoles, and benzotriazoles, can be efficiently employed as pronucleophiles in this transformation, providing expeditious access to N-cyclopropyl heterocycles.

This review covers rearrangements of cyclopropenes into aromatic five-membered heterocyclic compounds, namely furans and pyrroles; accompanied by small ring cleavage proceeding in the presence of catalytic amounts of transition metals, Lewis acids, or under UV irradiation.

Previously unknown boron-containing four-membered unsaturated heterocycle boretane was obtained via novel thermal rearrangement of cyclopropylborane and investigated by NMR and IR spectroscopy. Formation of boretane was also confirmed through its chemical transformation into more stable derivatives.

A diastereoconvergent formal nucleophilic substitution of bromocyclopropanes with oxygen- and sulfur-based nucleophiles is described. The reaction proceeds via in situ formation of a highly reactive cyclopropene intermediate and subsequent diastereoselective addition of a nucleophile across the strained C═C bond. Three alternative means of controlling the diastereoselectivity of addition have been demonstrated: (1) thermodynamically driven epimerization of enolizable carboxamides, (2) steric control by bulky substituents, and (3) directing effect of carboxamide or carboxylate functions.

A chemo- and diastereoselective protocol for the formal nucleophilic substitution of 2-bromocyclopropylcarboxamides with secondary amides is described. This method allows for convergent and highly selective synthesis of trans-β-aminocyclopropane carboxylic acid derivatives.

A new, general, and chemoselective protocol for the formal nucleophilic substitution of 2-bromocyclopropylcarboxamides is described. A wide range of alcohols and phenols can be employed as pronucleophiles in this transformation, providing expeditious access to trans-cyclopropanol ethers. A new mode of the selectivity control through a thermodynamic equilibrium is realized, alternative to the previously described steric and directing modes.

A highly diastereoselective formal nucleophilic substitution of bromocyclopropanes with oxygen- and nitrogen-based nucleophiles was demonstrated. The reaction proceeds via a base-assisted dehydrohalogenation producing a cyclopropene intermediate, which subsequently undergoes addition of a pronucleophile across the strained double bond. Very high chemoselectivity toward addition of primary and secondary alkoxides, as well as N-nucleophiles, in the presence of tert-butoxide base was observed, whereas phenoxides did not undergo addition under these reaction conditions. Facial selectivity of the addition can be efficiently controlled either by sterics or through a directing effect of an amide, carboxylate, and an o-aminomethylphenol function. Employment of tethered optically active amino alcohols as pronucleophiles allowed for efficient assembly of homochiral bicyclic compounds.

A series of novel chiral phosphanyl-oxazoline (PHOX) ligands possessing a cyclopropyl backbone were synthesized. It was shown that introduction of a strained cyclic fragment in the ligand platform helped restrict conformational fluctuations of the metallacycle and provided the catalyst with marked steric effects. It was demonstrated that insignificant alterations in the ligand structure had a dramatic influence on the stereochemical outcome of the intermolecular asymmetric Heck reaction.

A novel method for the assembly of medium heterocycles via an intramolecular nucleophilic addition to cyclopropenes generated in situ from the corresponding bromocyclopropanes is described. The exo-trig nucleophilic cyclizations were shown to proceed very efficiently and in a highly diastereoselective fashion affording cis-fused bicyclic products possessing 7 to 10-membered medium rings; starting from a diastereomeric mixtures of bromocyclopropanes.

An expeditious and cost-efficient method for synthesis of 1-arylcycloprop-2-ene-1-carboxamides was developed. This one-pot protocol involving coupling of amines with acyl chlorides, generated upon treatment of cyclopenylcarboxylic acids with oxalyl chloride, is applicable for the preparation of sensitive products with a reactive, unsubstituted strained double bond.

PPA-induced umpolung triggers efficient nucleophilic addition of unactivated anilines to nitroalkanes to produce N-hydroxyimidamides. The latter undergo sequential acid-promoted cyclocondensation with ortho-OH or ortho-NHR moieties to afford benzoxazoles and benzimidazoles, respectively.

A modular approach to 3-substituted 2-quinolones via a cascade annulation reaction between 4-nitroketones and hydrazines has been developed.

A one-pot synthesis of various GABA amides has been demostrated, employing the nucleophilic addition of primary and secondary amines across the double bond of cyclopropene-3-carboxamides, followed by ring-opening of the resulting donor–acceptor cyclopropanes and subsequent in situ reduction of enamine (imine) intermediates.

3-Substituted 2-quinolones are obtained via a novel, metal-free transannulation reaction of 2-substituted indoles with 2-nitroalkenes in polyphosphoric acid. The reaction can be used in conjunction with the Fisher indole synthesis offering a practical three-component heteroannulation methodology to produce 2-quinolones from arylhydrazines, 2-nitroalkenes and acetophenone.