Copper(II) Bromide/Boron Trifluoride Etherate‐Cocatalyzed Cyclization of Ketene Dithioacetals and p‐Quinones: a Mild and General Approach to Polyfunctionalized Benzofurans

Abstract

A new application of copper(II) bromideactivated ketene dithioacetals as nucleophiles in organic chemistry has been developed. Under the cocatalysis of copper(II) bromide (2.0 mol%) and boron trifluoride etherate (10 mol%), the conjugate addition and sequential cyclization of a-electron-withdrawing group-substituted ketene dithioacetals with p-quinones in acetonitrile at room temperature gave a variety of benzofurans. This formal [3 + 2] cycloaddition provides a general method for catalytic synthesis of polyfunctionalized benzofurans with the advantages of readily available starting materials, cheap catalysts, mild reaction conditions, good yields and wide range of synthetic potential for the benzofuran products. Further transformations of the resulting benzofurans to 2-aminobenzofurans and benzofuroA C H T U N G T R E N N U N G [2,3-d]pyrimidine derivatives are also investigated.

Unexpected Hydrobromic Acid‐Catalyzed CC Bond‐Forming Reactions and Facile Synthesis of Coumarins and Benzofurans Based on Ketene Dithioacetals

“…When catalyzed by CuCl 2 (10 mol %) or BF 3 ⋅Et 2 O (10 mol %) at room temperature for 48 or 35 h, 3 a was afforded only in 45 and 70 % yield, respectively (Table 1, entries 5 and 6) 9a. b Notably, with CuBr 2 (10 mol %) and BF 3 ⋅Et 2 O (10 mol %) as cooperative catalyst, the reaction was significantly accelerated (Table 1, entry 7 vs. entries 1 and 6). Taken together, the above results (Table 1, entries 1–7) suggest that CuBr 2 is a more effective catalyst than TiCl 4 , BF 3 ⋅Et 2 O, CuCl 2 , or CuBr, and that CuBr 2 plays a double role in both the activation of the carbonyl electrophiles and of the α‐CH bond of the ketene dithioacetals 8c.…”

“…Synthesis of benzofurans 7 through the reaction of ketene diethylthioacetals 1 and p ‐quinones 6 catalyzed by HBr : Recently, we reported that benzofurans 7 can be easily prepared by the reaction of CuBr 2 ‐activated ketene dimethylthioacetals 1 with BF 3 ⋅Et 2 O‐activated p ‐quinones 6 9b. In contrast, under the same conditions, no reaction was detected in the absence of BF 3 ⋅Et 2 O 9b. In this study, we found that all the reactions of 1 with 6 , except for the reaction between 1 i and 6 a , could also afford benzofurans 7 under the catalysis of only HBr (10 mol %).…”

“…Notably, in the latter cases, a wider range of substrates, including both ketene dithioacetals and electrophiles, are scalable with low catalyst loadings (10 mol %) 9. The significant acceleration of the CuBr 2 /BF 3 ⋅Et 2 O cocatalyzed reaction of 1 with aldehydes (Table 1, entry 7 vs. entries 1 and 6)9b seemed to give further support to the activation of 1 by CuBr 2 .…”

Palladium‐Catalyzed CS Activation/Aryne Insertion/Coupling Sequence: Synthesis of Functionalized 2‐Quinolinones

“…2a–d, 3a,b To our delight, 4‐phenyl‐2‐quinolinone9c–e ( 8 ) was separated from the reaction mixture in 79 % yield. Additionally, the direct substitution5e of the 4‐methylthio group of 3 m with phenylmethanamine was also performed to give the 4‐amino quinolinone 9 in high yield (Scheme ). Another application of 3 was presented in the synthesis of the pyrimidoquinolin‐5‐one 10 by the condensation of 3 m with acetimidamide (Scheme ).…”

Recent Advances in Metal‐Catalyzed Bond‐Forming Reactions of Ketene S,S‐Acetals

“…Furthermore, we designed and performed the CuBr 2 /BF 3 ⋅OEt 2 ‐co‐catalyzed [3+2] cyclization reaction of ketene S,S ‐acetals 1 and p ‐quinones 8 which provided a mild and general approach to polyfunctionalized benzofurans 9 (Scheme A) . This co‐catalytic strategy was also applied by Zeng's group in a multicomponent synthesis of 5‐aminobenzofurans 12 from aminophenols 10 and ketene S,S ‐acetals 1 (Scheme B) .…”