Cobalt-Catalyzed [6 + 2] Cycloaddition of Alkynes with 1,3,5,7-Cyclooctatetraene as a Key Element in the Direct Construction of Substituted Bicyclo[4.3.1]decanes

Abstract

A new, effective catalytic system based on Co(acac) has been developed for [6 + 2] cycloaddition of terminal alkynes to 1,3,5,7-cyclooctatetraene to give substituted bicyclo[4.2.2]deca-2,4,7,9-tetraenes in high yields (68-85%). The electrophilic activation of double bonds in the bicyclic products with m-CPBA is an efficient method for the synthesis of substituted bicyclo[4.3.1]deca-2,4,8-triene-7,10-diols, which form the key structural moieties of numerous natural biologically active compounds. The structures of the obtained compounds were reliably proven by modern spectral methods and X-ray diffraction. The mechanism of the discovered rearrangement was studied both using deuterium-labeled bicyclo[4.2.2]deca-2,4,7,9-tetraenes and utilizing quantum chemical calculations. The obtained substituted bicyclo[4.3.1]deca-2,4,8-triene-7,10-diols and their keto derivatives showed high antitumor activity in vitro against Hek293, Jurkat, K562, and A549 tumor cell lines.

Synthesis and Analysis of Substituted Bullvalenes

“…In 2006, Buono and co‐workers reported that cyclooctatetraene undergoes [6+2] cycloaddition reactions with alkynes to give substituted BDTs in the presence of a CoI 2 (dppe)/ZnI 2 /Zn catalyst system . This reaction has recently been reevaluated, revealing that a variety of Co II salts are viable precatalysts …”

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.…”

Synthesis of Functionally Substituted Bicyclo[4.2.1]nona-2,4-dienes and Bicyclo[4.2.1]nona-2,4,7-trienes by Cobalt(I)-catalyzed [6π + 2π] Cycloaddition of 2-Tropylcyclohexanone

“…Initially, we considered the catalytic reaction of 2-tropylcyclohexanone with allenes. The reaction was catalyzed by the efficient three-component system Co(acac) 2 (dppe)/Zn/ZnI 2 , which we developed previously and which proved to be active in the cyclocodimerization of 1,3,5-cyclooctatriene, 14 1,3,5,7-cyclooctatetraene, 15 and 1-substituted CHTs 9g with alkynes. It was shown that the [6π + 2π] cycloaddition of 2-tropylcyclohexanone 1 to allenes 2 catalyzed by the Co(acac) 2 (dppe)/Zn/ZnI 2 system under the conditions we developed [10 mol % Co(acac) 2 (dppe), 30 mol % Zn, 20 mol % ZnI 2 , DCE (1,2-dichloroethane), 20 h, 60 °C] affords substituted ( E )-bicyclo[4.2.1]nona-2,4-dienes 3a–c in 79–88% yields as a 1:1 mixture of syn - and anti -stereoisomers ( Table 1 ).…”