Deconstructive Reorganization: De Novo Synthesis of Hydroxylated Benzofuran

Abstract

An unprecedented deconstructive reorganization strategy for the de novo synthesis of hydroxylated benzofurans from kojic acid‐ or maltol‐derived alkynes is reported. In this reaction, both the benzene and furan rings were simultaneously constructed, whereas the pyrone moiety of the kojic acid or maltol was deconstructed and then reorganized into the benzene ring as a six‐carbon component. Through this strategy, at least one free hydroxyl group was introduced into the benzene ring in a substitution‐pattern tunable fashion without protection–deprotection and redox adjustment. With this method, a large number of hydroxylated benzofuran derivatives with different substitution‐patterns have been prepared efficiently. This methodology has also been shown as the key step in a collective total synthesis of hydroxylated benzofuran‐containing natural products (11 examples).

Skeletal reorganization divergence of N-sulfonyl ynamides

“…As shown in Table 1, we initially treated 1a with n-BuLi at −40°C for 1 h and then quenched with MeOH; a new major product 2a and a minor product 3a were isolated (entry 1). The standard analysis, including 1 H nuclear magnetic resonance (NMR), 13 C NMR and mass spectroscopy, was not able to identify these compounds. Gratifyingly, the X-ray analysis showed that 2a was a thiete sulfone and 3a was a propargyl sulfonamide (…”

“…6f, (β-13 C)-1a was prepared and subjected to the standard reactions. 13 C-2a and 13 C-3a could be formed smoothly under standard conditions. The position of 13 C-labelled carbon atom in the products was identified, which indicated that phenyl migration did not occur in these skeleton reorganization processes.…”

“…Very recently, Zhu and co-workers reported a novel skeletal reorganization of kojic acid-or maltol-derived alkynes under Indium catalysis, which provided an expeditious access to valuable hydroxylated benzofurans (Fig. 1d) 13 . Despite these advances, the investigation of skeletal reorganizations toward synthetically challenging and biologically interesting molecules remains continuously interesting and important.…”

Skeletal Reorganization Divergence of N-Sulfonyl Ynamides

“…We initially set the reaction using n-BuLi at -40 o C for 1 hour and then treated with MeOH, and a new major product 2a and a minor product 3a were observed (entry 1). The standard analysis, including 1 HNMR, 13 CNMR and mass spectroscopy, was not able to identify these compounds. Gratifyingly, the X-ray analysis showed that 2a was a thiete sulfone and 3a was a propargyl sulfonamide, indicating an unusual skeletal reorganization occurring.…”

“…Very recently, Zhu and coworkers reported a novel skeletal reorganization of kojic acid or maltol-derived alkynes under Indium-catalysis, which provided an expeditious access to valuable hydroxylated benzofurans ( Fig. 1d) 13 . Despite these advances, the investigation of skeletal reorganizations toward synthetically challenging and biologically interesting molecules remains continuous interesting and important.…”