Synthesis of new alkynyl containing 9-azabicyclo[4.2.1]nonatrienes from diynes and azepines

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

“…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. Please see the Supplementary Figures S13–S112 .…”

“…We previously reported [ 39 , 40 , 41 ] the development of an efficient one-pot synthesis of some substituted 9-azabicyclo[4.2.1]nona-2,4,7-trienes and 9-azabicyclo[4.2.1]nona-2,4-dienes based on the cobalt(I)-catalyzed cycloaddition of N -carbethoxy(phenoxy)azepines to alkynes, 1,3-diynes, and 1,2-dienes ( Scheme 2 ).…”

On the application of 3d metals for C–H activation toward bioactive compounds: The key step for the synthesis of silver bullets

“…Due to its accessibility, it is well explored in catalysis for many fields, such as cycloaddition reactions [175], polymerization [176], and C-C cross-coupling methods [177]. Several biologically active compounds have been obtained through cobalt catalysis [178][179][180] including its application in C-H activation reactions [181][182][183][184][185]. The synthesis of biologically important compounds using C-H activation techniques has been described by Ackermann and co-workers in 2019 [186].…”

Cobalt(I)-Catalyzed [6π + 2π] Cycloaddition of 1,2-Dienes and 1,3-Diynes to N-Carbocholesteroxyazepine in the Synthesis of Previously Undescribed Heterofunctional 9-Azabicyclo[4.2.1]nonadi(tri)enes

“…Earlier, 1 we have first presented an efficient one-pot method for the synthesis of substituted 9-azabicyclo[4.2.1]nona-2,4,7-trienes and 9-azabicyclo[4.2.1]nona-2,4-dienes based on cobalt(I)-catalyzed cycloaddition of the simplest N -carboalkoxyazepines to alkynes, 1,3-diynes, and 1,2-dienes. It is noteworthy that research work in the field of synthesis of new derivatives of 9-azabicyclo[4.2.1]nonanes is of high practical relevance, since the 9-azabicyclo[4.2.1]nonane backbone is a key structural element of a number of important alkaloids (anatoxin-a, 2 pinnamine, 3 and bis-homoepibatidine 4 ) with diverse biological activity ( Figure 1 ).…”

“…So far, there are only a few reported studies on the photochemical cyclocodimerization of tricarbonyl­(η 6 - N -carboalkoxyazepine)­chromium­(0) and tricarbonyl­(η 6 - N -cyanoazepine)­chromium­(0) with alkenes, 1,3-dienes, and alkynes. Moreover, before our studies started, , there had been no information available on the catalytic transformations of N-substituted azepines, except for two reactions of Cr(0)-catalyzed cycloaddition of N -carbomethoxyazepine and N -carbethoxyazepine to ethyl acrylate (Scheme ).…”