V. A. D’yakonov

Stereoselective synthesis of 11-phenylundeca-5Z,9Z-dienoic acid and investigation of its human topoisomerase I and IIα inhibitory activity.

(5Z,9Z)-11-Phenylundeca-5,9-dienoic acid was stereoselectively synthesized, based on original cross-cyclomagnesiation of 2-(hepta-5,6-dien-1-yloxy)tetrahydro-2H-pyran and buta-2,3-dien-1-ylbenzene with EtMgBr in the presence of Cp2TiCl2 catalyst giving 2,5-dialkylidenemagnesacyclopentane in 86% yield. The acid hydrolysis of the product and the Jones oxidation of the resulting 2-{[(5Z,9Z)-11-phenylundeca-5,9-dien-1-yl]oxy}tetrahydro-2Н-pyran afforded (5Z,9Z)-11-phenylundeca-5,9-dienoic acid in an overall yield of 75%. A high inhibitory activity of the synthesized acid with respect to human topoisomerase I (hTop1) and II (hTop2α) was determined.

Hydro-, Carbo-, and Cycloalumination of Unsaturated Compounds

This chapter gives a survey and a systematic account of modern achievements in the synthesis of acyclic and cyclic organoaluminum compounds using thermal and catalytic hydro- and carboalumination of unsaturated compounds. Here we consider a new, versatile catalytic cycloalumination reaction of olefins, acetylenes, and 1,2-dienes of various structures with alkyl and halogen alkyl Al catalyzed by Zr and Ti complexes to give previously unknown classes of OACs: aluminacyclopropanes, aluminacyclopropenes, aluminacyclopentanes, aluminacyclopentenes, aluminacyclopentadienes, and aluminamacrocarbocycles. Much attention is given to applications of hydro-, carbo-, and cycloalumination reactions for the synthesis of practically important natural carbo- and heterocyclic compounds.

Synthesis and transformations of metallacycles 40. Catalytic cycloalumination in the synthesis of 3-substituted phospholanes

An efficient one-pot method was developed for the synthesis of 3-alkyland 3-benzyl-substituted phospholanes through the successive Cp2ZrCl2-catalyzed cycloalumination of α-olefins in the presence of AlEt3 giving the corresponding aluminacyclopentanes followed by the in situ replacement of the aluminum atom in the latter compounds by a P atom by means of methyl(phenyl)dichlorophosphines. The oxidation of 3-alkyl- and 3-benzyl-1-methyl(phenyl)-phospholanes with hydrogen peroxide affords 3-alkyl- and 3-benzyl-1-methyl(phenyl)-phospholane 1-oxides, respectively.

First example of one-pot synthesis of hydrocarbon macrorings

Cyclomagnesation of α,ω-diallenes by EtMgBr in the presence of chemically activated Mg and Cp2TiCl2 catalyst led to the formation of cyclic organomagnesium compounds whose hydrolysis provided gigantic hydrocarbon macrorings with 1,5-cis-disubstituted double bonds.

Synthesis and transformations of metallacycles 41. Cyclomagnesiation of O-containing 1,2-dienes with Grignard reagents in the presence of Cp2TiCl2

A Cp2TiCl2-catalyzed intermolecular homocyclomagnesiation of O-containing 1,2-dienes and cross-cyclomagnesiation of O-containing 1,2-dienes with aliphatic 1,2-dienes of cyclic and acyclic structure have been accomplished using Grignard reagents, which led to mono- and bicyclic organomagnesium compounds in 61–94% yields.

First synthesis of magnesacyclopentadienes from acetylenes by treatment with BuMgHlg in the presence of Zr complexes

Treatment of internal acetylenes and allenes with BuMgHlg (Hlg = Cl, Br) in the presence of Cp2ZrCl2 selectively leads to the formation of substituted magnesacyclopenta-2,4-dienes and alkylidenemagnesacyclopentenes.

Catalytic cyclometallation in steroid chemistry III: Synthesis of steroidal derivatives of 5Z,9Z-dienoic acid and investigation of its human topoisomerase I inhibitory activity

Two approaches to stereoselective synthesis of steroid 5Z,9Z-dienoic acids were developed, the first one being based on the cross-cyclomagnesiation of 2-(hepta-5,6-dien-1-yloxy)tetrahydro-2H-pyran and 1,2-diene cholesterol derivatives on treatment with EtMgBr catalyzed by Cp2TiCl2, while the other involving the synthesis of esters of hydroxy steroids with (5Z,9Z)-tetradeca-5,9-dienedioic acid, prepared in two steps using homo-cyclomagnesiation of 2-(hepta-5,6-dien-1-yloxy)tetrahydro-2H-pyran as the key step. High inhibitory activity of the synthesized acids against human topoisomerase I (hTop1) was found.

Stereoselective Synthesis of Trisubstituted Olefins through 2,5-Dialkylidenemagnesacyclopentanes

An efficient one-pot procedure for the synthesis of trisubstituted olefins with Z-configured double bonds has been developed on the basis of cross coupling of 2,5-dialkylidenemagnesacyclopentanes (generated in situ) with alkyl, allyl, and aryl halides in the presence of transition metal (Cu, Zr, Fe, Co, Ni, Pd) salts and complexes.

Synthesis and transformations of metallacycles 43. One-pot synthesis of polycyclic 3-alkyl(phenyl)phospholane 3-oxides

A one-pot method for the synthesis of polycyclic phospholanes and phospholane 3-oxides from norbornenes was developed based on their Cp2ZrCl2-catalyzed cycloalumination. The in situ formed polycyclic aluminacyclopentanes were treated with organic dichlorophosphines (RPCl2, where R = Me, But, Ph) to obtain polycyclic phospholanes. The phospholanes were oxidized with hydrogen peroxide to obtain their 3-oxides in 81–92% yields.

Catalytic hydroamination of fullerene C60 with primary and secondary amines

Catalytic 1,2-hydroamination of fullerene C60 with primary and secondary amines in the presence of Ti, Zr, and Hf complexes gave the corresponding alkyl-, aryl-, and hetarylaminodihydrofullerenes.