Cobalt‐Catalyzed Regioselective Synthesis of Indenamine from o‐Iodobenzaldimine and Alkyne: Intriguing Difference to the Nickel‐Catalyzed Reaction

Abstract

Indene derivatives [1,2] are known to show various pharmacological properties, such as enzyme inhibitors, [1a] reuptake blocking, [1b] biogenic transporters, [1c] and anti-arrhythmic activity.[1d] In addition, they have also found applications in material science as discotic liquid crystals, [1e] coating materials for steel, [1f] conducting polymers, [1g] ligands for metallocene complexes, [1h,i] and so forth. Indenamine derivatives were recently synthesized by reacting chloroindan [1c] with the desired amines and by nucleophilic addition into nitrile derivatives, [3a] whereas indenones were prepared by oxidation of the corresponding indene derivatives [3b] and by catalytic intramolecular isomerization-aldolization [3c] of allyl alcohol with aldehyde. In this paper, we report a new convenient method for the regioselective synthesis of indenamine from the corresponding o-halobenzaldehyde, amine, and alkyne in the presence of zinc powder catalyzed by cobalt complexes. Moreover, these compounds can be conveniently converted to the corresponding substituted indenone derivatives.Recently, we and other groups had found methods for the synthesis of isoquinoline derivatives [4] from 2-iodobenzaldimines (1) and alkynes catalyzed by nickel [4a] and palladium complexes, respectively.[4b-f] Our interests in the cobalt-catalyzed reactions [5] and the recent observation of activation of arylhalides by cobalt complexes [5] have prompted us to investigate the use of cobalt complexes for the reaction of Ntert-butyl-2-iodobenzaldimine (1 a) with alkyne. To our surprise, when we treated 1 a with 4-octyne in the presence of [CoCl 2 A C H T U N G T R E N N U N G (dppe)] and zinc powder in acetonitrile, the corresponding indenamine (5 a; Scheme 1, R 1 = R 2 = nPr) was obtained in 78 % yield. This is in sharp contrast to the nickel- [4a] and palladium-catalyzed [4b-f] reactions that gave the corresponding isoquinoline derivative as product. The structure of the indenamine was established based on its 1 H, 13C NMR, and MS spectral data.To simplify the reaction, we observed that by using the corresponding o-iodobenzaldehyde and amine to replace 1 a, the same indenamine product can be obtained. Thus, o-iodobenzaldehyde (2 a), p-toluidine (3 a), and 4-octyne underwent three-component reaction in the presence of [CoCl 2 -A C H T U N G T R E N N U N G (dppe)] in an acetonitrile and THF mixture (optimization studies are given in the Supporting Information) to afford indenamine 5 b in essentially quantitative yield (entry1, Table 1). In a similar manner, diphenylacetylene (4 b) afforded product 5 c in 78 % yield. The three-component reactions of unsymmetrical alkynes with 2 a and 3 a were carefully studied by using the same catalyst system. Terminal alkyne 4 c gave a single regioisomer 5 d with the propyl group adjacent to the amino group in 82 % yield (entry 3). For disubstituted unsymmetrical alkyne 4 d, two regioisomers 5 e (R 1 = Ph, R 2 = Et) and 5 e (R 1 = Et, R 2 = Ph) in 60 and 36 % yields, respectively, were observed. T...

Ruthenium(II)‐Catalyzed CH Bond Activation: An Efficient Route toward Indenamines

“…[13] Similarly, these N-tosylindenamines are easily converted into the corresponding indenones with tetrabutylammonium fluoride (Scheme 5). [14] …”

Facile synthesis of indene and fluorene derivatives through AlCl3‐catalyzed cyclization of in situ formed iminium ions

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Cobalt‐Catalyzed Dual Annulation of o‐Halobenzaldimine with Alkyne: A Powerful Route toward Bioactive Indenoisoquinolinones

“…Recently, we observed the cyclization of o ‐halobenzaldimines with alkynes in the presence of cobalt complexes to give indenamine products, regioselectively 4a. The Indenamine derivative I was obtained if the loaded alkyne did not contain an electron‐withdrawing group.…”