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A new ionic cyclopropanation process involving the addition of diazo esters to donor-acceptor cyclopropanes (DAC) activated by GaCl3 has been developed. The reactions occur via 1,2-zwitterionic gallium complexes with elimination of nitrogen in all cases to give 1,1,2,3-tetrasubstituted cyclopropanes as the main products. Also, a number of related processes with the formation of various polysubstituted cyclopropanes, alkenes, and cyclobutanes, including products of multiple diazo ester addition, have been developed. Obtained by the developed method tetrasubstituted cyclopropanes are activated cyclopropanes such as DAC and can be used for further synthesis in this capacity. Their new reaction with benzaldehyde promoted by TiCl4 and involving one of the additional functional groups has been demonstrated, which leads to five-membered lactones. The mechanisms of the occurring processes, as well as the structures and stereochemistry of a rich range of products formed, are discussed in detail.

The reactions of 1,2-zwitterionic complexes, generated from 2-arylcyclopropane-1,1-dicarboxylates (ACDC) or benzylidenemalonate and gallium trichloride, with benzyl azide proceeds as a formal [3+2] cycloaddition to form dihydro-1,2,3-triazoles. The latter, when the reaction mixture is treated with 10% aqueous HCl, undergo retrocyclization with elimination of diazomalonate. The reaction of ACDC, benzyl azide, and GaCl3 with simultaneous mixing of the reagents leads to the interception of the 1,3-zwitterion, with this stage being accompanied by both the cyclization to substituted 1,2,3-triazinine and the elimination of a nitrogen molecule to form 3,4-dihydro-2H-1,2-oxazine structure, which after acid hydrolysis gives substituted 3-hydroxypyrrolidin-2-one.

Aim. The aim of the study is to examine the efficacy and safety of eribulin in HER2-negative metastatic breast cancer (BC) in Russian clinical practice. Materials and methods. The analysis included 459 patients with advanced BC from 44 federal and municipal medical clinics in Russia and received at least 2 courses of treatment with eribulin in accordance with the registered indications for drug. The average age of women was 56 years (between 29 and 81 years), 83% of patients had HER2-negative tumor subtype (49.9% - luminal BC and 33.1% - triple-negative BC) HER2-positive biological tumor subtype was registered in 17% of patients. Visceral metastases were diagnosed in 73% of patients and three-zone and multiple zone metastases were diagnosed in 41.6% of cases. The median number of prior lines of therapy in patients with disseminated disease was 2; anthracycline and taxane chemotherapy was applied in 94.3% of patients, and 38.1% of patients were recived CT plus capecitabine. Standard treatment regimen with eribulin was cotinuing (1.4 mg/m² as a 2-5-minute intravenous infusion administrated on days 1, 8 of a 21-day cycle) until disease progression, unacceptable toxic effects, or impossibility of the drug administration for any other reason. We estimated the efficacy and safety of treatment with eribulin in Russian patients with HER2-negative BC. Results. Objective response rate was achieved in 20.5% of cases, complete response rate was in 3.2%, partial - 17.3%, and the stable disease rate was marked in 52.7% of women, and in 19.7% of these cases was prolonged more than 6 months. The frequency of objective response was higher in luminal BC group compared with triple-negative BC: 23.5% vs 15.8%; tumor growth control 76.9% vs. 67.8%, respectively; p

2-Styrylcyclopropane-1,1-dicarboxylate treated with anhydrous gallium trichloride undergoes dimerization with the cyclopropane ring opening and the styryl substituent double bond involvement, leading to the formation of polysubstituted cyclic and bicyclic structures with the predominance of the former or the latter depending on the reaction conditions. Most compounds are formed with very high diastereoselectivity. Thirteen major and minor dimeric structures were isolated and reliably characterized, two of which were found to additionally include a chlorine atom. A rare for the reactions of donor-acceptor cyclopropanes example of the formation of a product with the fused cyclobutane ring was effected at–80 °C. Plausible mechanisms of observed processes were discussed.

A new process for isomerization of donor–acceptor cyclopropanes (2-arylcyclopropanedicarboxylates) by treatment with anhydrous gallium trichloride to give (2-arylalkylidene)malonates in high yields and with good selectivity has been developed. The reaction involves initial formation of a 1,2-dipolar gallium complex.

A series of novel gallium dimethylmalonate and cyclopropane-1,1-dicarboxylate complexes have been synthesized using gallium halides as Lewis acids. The structure and properties of the resulting complexes as well as the mechanisms of reactions involved have been studied. Some complexes have ionic structures and consist of ligand-bound Ga cations and tetrahalogallate anions. The structures of gallium complexes were studied by multinuclear NMR spectroscopy, including that on 71Ga nuclei. Furthermore, X-ray diffraction analysis was carried out for the six complexes. Dimethyl cyclopropanedicarboxylate was considered as the simplest analogue of donor–acceptor cyclopropanes. It is a convenient model for studying such cyclopropanes, while the complexes obtained are analogues of intermediates in their reactions catalyzed by Lewis acids. In particular, elongation of the C–CH2 bond in the cyclopropane ring and activation of the latter by gallium halides have been shown experimentally. The data obtained are a new ste...

A new process for (4 + 2)-annulation of donor-acceptor cyclopropanes (DACs) with unsaturated compounds in the presence of anhydrous GaCl3 has been developed. In this process, DACs act as sources of formal 1,2- and 1,4-dipoles to give polysubstituted tetralins in high yields and with high regio- and diastereoselectivity. Alkenes with both aryl and alkyl substituents at the double bond undergo this reaction equally readily. A most likely mechanism of the reaction has been proposed. It involves preliminary generation of a key 1,2-dipolar gallium complex and its subsequent participation in annulation with an alkene.

Substituted naphthalenes were obtained by treatment of a mixture of two different 2-arylcyclopropane-1,1-dicarboxylates with GaCl3 at 80 ℃. The process is accompanied by removal of the malonic moieties, naphthalene fragments being mainly formed from the arylcyclopropane, which is more prone to give the similar homocoupling product.

A new type of donor-acceptor cyclopropane reactivity has been discovered. On treatment with anhydrous GaCl3 , they react as sources of even-numbered 1,2- and 1,4-dipoles instead of the classical odd-numbered 1,3-dipoles due to migration of positive charge from the benzyl center. This type of reactivity has been demonstrated for new reactions, namely, cyclodimerizations of donor-acceptor cyclopropanes that occur as [2+2]-, [3+2]-, [4+2]-, [5+2], [4+3]-, and [5+4]-annulations. The [4+2]-annulation of 2-arylcyclopropane-1,1-dicarboxylates to give polysubstituted 2-aryltetralins has been developed in a preparative version that provides exceedingly high regio- and diastereoselectivity and high yields. The strategy for selective hetero-combination of donor-acceptor cyclopropanes was also been developed. The mechanisms of the discovered reactions involving the formation of a comparatively stable 1,2-ylide intermediate have been studied.

A new type of dimerization of 2-arylcyclopropane-1,1-dicarboxylates in the presence of anhydrous GaCl3 to give acyclic dimers, viz., substituted pent-2-ene-1,1,5,5-tetracarboxylates, occurs at room temperature. In this reaction, one molecule of the donor–acceptor cyclopropane manifests a non-classical reactivity and serves as a 1,2-dipole.

A new process for isomerization of donor–acceptor cyclopropanes (2-arylcyclopropanedicarboxylates) by treatment with anhydrous gallium trichloride to give (2-arylalkylidene)malonates in high yields and with good selectivity has been developed. The reaction involves initial formation of a 1,2-dipolar gallium complex.

A new type of dimerization of 2-arylcyclopropane-1,1-dicarboxylates in the presence of anhydrous GaCl3 to give acyclic dimers, viz., substituted pent-2-ene-1,1,5,5-tetracarboxylates, occurs at room temperature. In this reaction, one molecule of the donor–acceptor cyclopropane manifests a non-classical reactivity and serves as a 1,2-dipole.

Dimethyl 2-arylcyclopropane-1,1-dicarboxylates on heating with GaCl 3 undergo dimerization to afford arylnaphthalenes or phenanthrenes. A possible reaction mechanism including elimination of two dimethyl malonate molecules was proposed, dimethyl malonate gallium complex Ga 3+ [H 2 C(CO 2 Me) 2 ] 3 (GaCl – ) was isolated and characterized by X-ray diffraction analysis.

In this new process donor-acceptor cyclopropanes act as sources of formal 1,2- and 1,4-dipoles to afford polysubstituted tetralins in a regio- and diastereoselective manner.

Dimethyl 2-arylcyclopropane-1,1-dicarboxylates on heating with GaCl 3 undergo dimerization to afford arylnaphthalenes or phenanthrenes. A possible reaction mechanism including elimination of two dimethyl malonate molecules was proposed, dimethyl malonate gallium complex Ga 3+ [H 2 C(CO 2 Me) 2 ] 3 (GaCl – ) was isolated and characterized by X-ray diffraction analysis.

A new type of donor–acceptor cyclopropane reactivity has been discovered. On treatment with anhydrous GaCl3, they react as sources of even-numbered 1,2- and 1,4-dipoles instead of the classical odd-numbered 1,3-dipoles due to migration of positive charge from the benzyl center. This type of reactivity has been demonstrated for new reactions, namely, cyclodimerizations of donor–acceptor cyclopropanes that occur as [2+2]-, [3+2]-, [4+2]-, [5+2]-, [4+3]-, and [5+4]-annulations. The [4+2]-annulation of 2-arylcyclopropane-1,1-dicarboxylates to give polysubstituted 2-aryltetralins has been developed in a preparative version that provides exceedingly high regio- and diastereoselectivity and high yields. The strategy for selective hetero-combination of donor–acceptor cyclopropanes was also been developed. The mechanisms of the discovered reactions involving the formation of a comparatively stable 1,2-ylide intermediate have been studied.