Copper-Catalyzed Cascade Synthesis of 2-Aryl-3-cyanobenzofuran and Dibenzo[b,f]oxepine-10-carbonitrile Derivatives

Abstract

The copper-catalyzed reaction of aryl aldehydes with 2-iodobenzylcyanides afforded 2-aryl-3-cyanobenzofurans in isolated yields of up to 74% in a cascade manner, which involves Knoevenagel condensation, aryl hydroxylation, oxa-Michael addition, and aromatization reactions. Conversely, 2-halo benzaldehydes as reacting partners with 2-iodobenzylcyanide regioselectively furnished dibenzo[ b,f]oxepine-10-carbonitrile derivatives up to 85% isolated yields via tandem Knoevenagel condensation, aryl hydroxylation, and Ullmann coupling reactions.

Design, Synthesis and Biological Evaluation of Stilbene Derivatives Containing a 1,3‐Benzodioxole Moiety

“…In order to obtain the target molecules conveniently, the large‐scale synthesis of the key diarylethene intermediates 2 is the most important. In fact, the first step of transformation is a similar reaction of classical Knoevenagel condensation reaction, which can be processed by several methods [26,27] . However, we desire to obtain a convenient and effective procedure for these intermediates with specific substituents, and the transformation condition was initially optimized using 3,4‐methylenedioxyphenylacetic acid 1 and 3,4,5‐trimethoxybenzaldehyde as substrates, and the different base were explored as catalyst.…”

“…In fact, the first step of transformation is a similar reaction of classical Knoevenagel condensation reaction, which can be processed by several methods. [26,27] However, we desire to obtain a convenient and effective procedure for these intermediates with specific substituents, and the transformation condition was initially optimized using 3,4-methylenedioxyphenylacetic acid 1 and 3,4,5-trimethoxybenzaldehyde as substrates, and the different base were explored as catalyst. The results indicated that the reaction catalyzed by DIPEA give the best isolated yields (74 %), however, the intermediate 2 b (R 1 = OCH 3 ) can also be obtained using triethylamine (42 %) and pyridine (56 %) with relatively low yields respectively.…”

Pd/C and TFA‐promoted One‐pot, Two‐step Cascade Reaction: An Effective Synthesis of Oxepines

“…Of late, Panda and coworkers described the synthesis of phenyldibenz[ b,f ]oxepines in two steps involving Sonagashira reaction between o ‐iododiaryl ethers and terminal alkyne to give 2‐phenoxy diaryl acetylenes in the first step, followed by FeCl 3 ‐catalyzed intramolecular C−H hydroarylation in the second step (Scheme 1a) [19a] . Later, Yao and coworkers demonstrated on the synthesis of substituted dibenzo[ b,f ]oxepine‐10‐carbonitrile via copper‐catalyzed cascade reaction of 2‐halo benzaldehydes with 2‐iodobenzylcyanide, however, the scope of the method was limited (Scheme 1b) [19b] . However, these previous reported methods for the construction of the oxepines require long reaction times, high reaction temperatures, and step‐by‐step procedure to obtain the oxepine derivatives.…”

An overview on the copper‐promoted synthesis of five‐membered heterocyclic systems

“…Disubstituted aldehydes could successfully undergo the cascade reaction to afford 2‐aryl‐3‐cyanobenzofurans. The method was then extended to substituted and disubstituted 2‐iodobenzylcyanide substrates, producing corresponding 2‐aryl‐3‐cyanobenzofurans (Scheme ) …”