An efficient and convenient nickel-catalyzed cyclization of 2-iodoanilines with alkynyl aryl ketones to give 2,4-disubstituted quinolines was developed. The reaction can be employed for the synthesis of naturally occurring quinoline derivatives in good yields. On the basis of the regiochemistry of the products, the possible pathway for the reaction is via the formation of o-aminochalcone.

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...

An efficient short total synthesis of benzo[c]phenanthridine alkaloids including oxyavicine, oxynitidine, and oxysanguinarine is described. Thus, N-methyl-o-bromobenzaldimines 1 b-d undergo regioselective cyclization with 4-(benzo[d][1,3]dioxol-5-yl)but-3-yn-1-ol (2 b) in the presence of [Ni(cod)(2)] (cod=1,5-cyclooctadiene). In situ oxidation of the resultant isoquinolinium salts gives isoquinolinone derivatives 5 b-d with benzo[d][1,3]dioxol-5-yl substitution at the C(3) atom and a (CH(2))(2)OH group at the C(4) atom. Later, oxidation of the alcohol group in 5 b-d to the aldehyde moiety followed by acid-catalyzed cyclization and dehydration completes the total syntheses to give oxyavicine, oxynitidine, and oxysanguinarine in 67, 65, and 60 % yields, respectively. The synthesis requires four steps from o-bromobenzaldehyde derivatives. Transformations of these alkaloids to the other alkaloids in this family are also discussed herein.

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The reductive coupling of an aryl carbonyl group with an activated alkene to give the corresponding γ‐hydroxybutyric acid (GHBA) derivative was achieved in the presence of zinc and ammonia. A board scope of GHBA derivatives could be synthesized under ambient conditions by this method. A mechanism involving a Zn‐ketyl radical as the key intermediate is proposed.