Co(I)-Catalyzed [4 π + 2 π ] Cycloaddition of 1,2-Dienes to 1,3,5-Cyclooctatriene in the Synthesis of Previously Undescribed Tricyclo[4.2.2.0 2,5 ]Decenes †

The catalytic [4 π + 2 π ]-cycloaddition of monosubstituted and disubstituted 1,2-dienes to 1,3,5-cyclooctatriene under the action of Co(acac) 2 (dppe)/Zn/ZnI 2 was performed for the ﬁrst time to produce substituted tricyclo[4.2.2.0 2,5 ]dec-7-enes.


Introduction
Over the past decades, bicyclic and polycyclic and cage hydrocarbons and their functionally substituted derivatives have been the objects of close attention of synthetic chemists due to their wide use as promising precursors for the development of modern drugs, important biologically active compounds and other practically valuable substances [1]. However, on the way to the widespread use of bicyclic and polycyclic compounds, both in laboratory practice and in industry, there are a number of difficulties associated with the inaccessibility of the feedstock for obtaining polycarbocycles of a given structure, the multistage synthesis for the isolation and purification of target compounds. Therefore, the development of one-pot methods for directed synthesis of previously hard-to-reach carbocycles and heterocarbocycles is an important and urgent problem of modern organic chemistry.
An analysis of the world literature shows that the number of promising and widespread methods for the synthesis of bi-and polycyclic compounds include catalytic cycloaddition reactions with the participation of available cyclic trienes [2][3][4][5][6]. In this area of research, 1,3,5-cyclooctatriene (COT) is of particular interest. However, the reactions of catalytic cycloaddition with the participation of this monomer have hardly been studied, and they are represented by works on Mo-catalyzed and Co-catalyzed cyclodimerization of COT [7,8].

Experimental Part
Chromatographic analysis was performed on a chromatograph using a 2000 × 2 mm column (SE-30 (5%) stationary phase on Сhromaton N-AW-HMDS (0.125-0.160 mm), helium carrier gas (30 mL/min) and temperature programming from 50 to 300 °C at an 8 °C/min rate. Flash column chromatography was performed over silica gel 0.060-0.200 mm, 60 A. 1 H and 13 C NMR spectra were recorded in CDCl3 at 125 MHz for 13 C and 500 MHz for 1 H. The chemical shifts are reported as δ values in parts per million relative to the internal standard Me4Si. The coupling constants (J) are reported in hertz.
High-resolution mass spectra (HRMS) were measured on an instrument using a timeof-flight mass analyzer (TOF) with electrospray ionization (ESI). In experiments on selective collisional activation, the activation energy was set at a maximum abundance of fragment peaks. A syringe injection was used for solutions in MeCN/H2O, 50/50 v/v (flow rate In a previous study [10,12,14,17], we found that substituted bicyclo  (Table 1). We found that tricyclic adducts 4a,b exhibit a cytotoxic effect and the inhibitory concentration values are in the range of IC 50 = 0.019 ± 0.002-0.045 ± 0.004 µM.

Experimental Part
Chromatographic analysis was performed on a chromatograph using a 2000 × 2 mm column (SE-30 (5%) stationary phase on Chromaton N-AW-HMDS (0.125-0.160 mm), helium carrier gas (30 mL/min) and temperature programming from 50 to 300 • C at an 8 • C/min rate. Flash column chromatography was performed over silica gel 0.060-0.200 mm, 60 A. 1 H and 13 C NMR spectra were recorded in CDCl 3 at 125 MHz for 13 C and 500 MHz for 1 H. The chemical shifts are reported as δ values in parts per million relative to the internal standard Me 4 Si. The coupling constants (J) are reported in hertz.
High-resolution mass spectra (HRMS) were measured on an instrument using a timeof-flight mass analyzer (TOF) with electrospray ionization (ESI). In experiments on selective collisional activation, the activation energy was set at a maximum abundance of fragment peaks. A syringe injection was used for solutions in MeCN/H 2 O, 50/50 v/v (flow rate 3 mL/min). Nitrogen was applied as a dry gas; the interface temperature was set at 180 • C. All reactions were carried out under a dry argon atmosphere. 1,2-Dichloroethane was dried and freshly distilled before use. Co(acac) 2 (dppe), 1,2-dienes and COT were synthesized according to procedures described in the literature [18][19][20].
Cycloaddition of 1,2-dienes to COT (general procedure). Zn powder (30 mol%) was added to a solution of Co(acac) 2 (dppe) (10 mol%) in C 2 H 4 Cl 2 (1.5 mL) in a Schlenk tube under a dry argon atmosphere, and the mixture was stirred at room temperature for 2 min. Next, COT (1.0 mmol), the 1,2-dienes (1.3 mmol) in C 2 H 4 Cl 2 (1.5 mL) and dry ZnI 2 (20 mol%) were added successively. After heating at 60 • C for 20 h, the reaction was stopped by the addition of a petroleum ether and stirred in air for 10 min to deactivate the catalyst. After filtration through a short pad of silica, the volatiles were removed under vacuum. Chromatographic purification over SiO 2 (petroleum ether → petroleum ether / ethyl acetate 30:1 as eluent) afforded the target products 4a,b.  13