The Synthesis of Bicyclo[4.2.1]nona-2,4,7-trienes by [6π + 2π]-Cycloaddition of 1-Substituted 1,3,5-Cycloheptatrienes Catalyzed by Titanium and Cobalt Complexes

Abstract

The [6π + 2π]-cycloaddition of alkynes to 1-methyl-, propyl-, benzyl-, and hydroxymethyl-substituted 1,3,5cycloheptatrienes in the presence of catalytic systems Ti(acac) 2 Cl 2 -Et 2 AlCl and Co(acac) 2 (dppe)/Zn/ZnI 2 was performed for the first time to give practically valuable bicyclo[4.2.1]nona-2,4,7-trienes in high yields (72−88%). The structures of the obtained bicyclic compounds were reliably proved by NMR methods and X-ray diffraction analysis. The newly synthesized bicycles have been investigated for their in vitro cytotoxic activity against Jurkat, K562, U937, and HL60 tumor and normal cell lines and induction of apoptosis.

Synthesis of New Functionally Substituted 9-Azabicyclo[4.2.1]nona-2,4,7-trienes by Cobalt(I)-Catalyzed [6π + 2π]-Cycloaddition of N-Carbocholesteroxyazepine to Alkynes

“…Our experiments clearly demonstrated the Co(acac) 2 (dppe)/Zn/ZnI 2 three-component catalytic system [ 52 , 53 , 54 , 55 , 56 , 57 ] being not only tolerant but equally efficient for a large variety of the substituents (alkyl, phenyl, p- halophenyl, alcohol, nitrile, ester, sulfide, phthalimide, cycloalkane, naphthalene, and phenanthrene) in the starting alkynes.…”

“…With N -carbocholesteroxyazepine 2 in our hands, we investigated its cycloaddition to the terminal alkynes 3a–t . Thus, we found that the desired [6π + 2π]-cycloaddition process occurred, being catalyzed by the Co(acac) 2 (dppe)/Zn/ZnI 2 (dppe-1,2-bis(diphenylphosphino)ethane) system [ 52 , 53 , 54 , 55 , 56 , 57 ] under developed conditions (10 mol% Co(acac) 2 (dppe), 30 mol% Zn, and 20 mol% ZnI 2 , in DCE (1,2-dichloroethane) as solvent, for 20 h at 60 °C) to afford substituted 9-azabicyclo[4.2.1]nona-2,4,7-trienes 4a–t with 79–95% yields ( Scheme 5 ). The adducts were formed as two N-(CO)O-cholesteryl rotamers [ 33 , 34 , 39 , 40 , 41 ] in a 1:1 ratio, arising due to hindered rotation of the substituent around the CN bond.…”

New in the Catalytic Synthesis of Practically Important Eight- and Nine-Membered Carbocycles by Cycloaddition Reactions with the Participation of 1,3,5-Cycloheptatrienes and 1,3,5,7-Cyclooctatetraenes

“…It was found that [6π + 2π] cycloaddition of nitrogen-4 and silicon-containing alkynes 5 to CHTs 1 under the action of the Ti(acac)2Cl2-Et2AlCl catalytic system in benzene for 8-24 h at 80 °C leads to the formation of bicyclo Of particular interest are the works [24,25] on the reactions of cyclocodimerization of bis(1,3,5-cycloheptatriene-7-yl)alkanes-monomers containing in their structure simultaneously two cycloheptatriene fragments, which means two reaction centers. We found that as a result of the interaction of bis( 1 In 2019, we studied the cyclocodimerization reactions of 1-substituted CHTs [26]. We found 1-methyl(benzyl)-1,3,5-cycloheptatrienes 11 enter into a [6π + 2π]-cycloaddition reaction with Si-containing alkynes 5 under the action of the catalytic system Ti(acac)2Cl2-Scheme 2.…”

“…In 2019, we studied the cyclocodimerization reactions of 1-substituted CHTs [26]. We Et2AlCl (5 mol% Ti(acac)2Cl2, Ti/Al = 1:20, C6H6, 80 °C, 8 h) to form substituted bicyclo[4.2.1]nona-2,4,7-trienes 13 as a single regioisomer.…”

“…We Et2AlCl (5 mol% Ti(acac)2Cl2, Ti/Al = 1:20, C6H6, 80 °C, 8 h) to form substituted bicyclo[4.2.1]nona-2,4,7-trienes 13 as a single regioisomer. Similarly, under the developed conditions (15 mol% Ti(acac)2Cl2, Ti/Al = 1:20, C6H6, 80 °C, 8 h), we managed to carry out the cyclodimerization of 1-methylcycloheptatriene 11 with propargylamines 4 to obtain nitrogen-containing bicyclo[4.2.1]nona-2,4,7-trienes 14 in high yields (76-88%) [26] (Scheme 4). It should be emphasized that [6π + 2π]-cycloadducts of COTT with alkynes-bicyclo[4.2.2]deca-2,4,7,9-tetraenes are widely used as key synthons in the preparation of practically valuable natural and synthetic biologically active compounds [28][29][30][31].…”