Synergistic Effect of Palladium and Copper Catalysts: Catalytic Cyclizative Dimerization of ortho‐(1‐Alkynyl)benzamides Leading to Axially Chiral 1,3‐Butadienes

Abstract

Two is better than one: In the presence of Pd(OAc)(2) and Cu(OAc)(2), o-(1-alkynyl)benzamides 1 were converted into bis-iminobenzoisofurans with an axially chiral 1,3-diene 2 unit. The coexistence of both Pd and Cu catalysts was found to be essential for both the cyclizative dimerization process and for the observed unusual cyclization mode.

Palladium‐Catalyzed Regioselective 5‐exo‐O‐Cyclization/Oxidative Heck Cascades from o‐Alkynylbenzamides and Electron‐Deficient Alkenes

“…In those three reactions, the formation of oxidative dimerization product 6a was also observed. The preparation of products of type 6 from o ‐alkynylbenzamides 1 has recently been reported in the literature under the combined action of catalytic Pd II and Cu II 5. Not surprisingly, Pd(OAc) 2 /PPh 3 , without added acetate anion, triggered a very predominant 5‐ exo ‐cyclization (Table 1, entry 8), with an overall exo / endo ratio of 91:9 (including the formation of 6a ).…”

“…The imino functionality of imidates 4 can be hydrolyzed under acidic conditions,5,15 as exemplified by the conversion of 4e and 4i into the corresponding lactones 8 in high yields (Scheme ). As a result, a two‐step route to 3‐allylideneisobenzofuranones appears to be established, using o ‐alkynylbenzamides as starting materials.…”

“…Ethyl ( E )‐4‐{(1 Z ,3 Z )‐3‐[(4‐Methoxyphenyl)imino]isobenzofuran‐1(3 H )‐ylidene}‐4‐phenylbut‐2‐enoate (4j): Prepared from 1j (77.0 mg, 0.235 mmol) and ethyl acrylate (513 μL, 4.7 mmol), using PdCl 2 (PPh 3 ) 2 (5 mol‐%) as catalyst, and KOBz (10 mol‐%) instead of DMAP. The crude was purified by flash chromatography (silica gel saturated with Et 3 N, hexanes/EtOAc/Et 3 N, 95:4:1 to 60:39:1), to give 4j (72 mg), 5j 8 (2 mg, 2 %), and 6c 5 (5.7 mg, 8 %). Product 4j was further purified by stirring for 16 h at room temperature in hexanes (5 mL).…”

“…For example, products derived from the 5‐ exo ‐heterocyclization mode were obtained with aryl halide coupling agents 4. Similarly, oxidative dimerization5 and oxidative coupling to an o ‐alkynylaniline6 or carbon monoxide7 are also 5‐ exo ‐selective reactions. On the other hand, the corresponding oxidative coupling reactions of o ‐alkynylbenzamides with electron‐deficient alkenes have provided products 5 derived from 6‐ endo ‐cyclizations 8–10.…”

Corrigendum: A General Synthesis of Alkenyl‐Substituted Benzofurans, Indoles, and Isoquinolones by Cascade Palladium‐Catalyzed Heterocyclization/Oxidative Heck Coupling

“…[4] In the present case, the initial heterocyclization from 7 is followed by an oxidative intermolecular Heck-type coupling (Scheme 6 in the original manuscript, in which Y = À CONR) leading to 1H-isochromen-1-imine derivatives (11). These are interesting compounds [5] not only for being the nitrogen analogues of the biologically important isocoumarins but also because of their own properties.…”