Synthesis of Highly Substituted Benzofuran–containing Natural Products via Rh–catalyzed Carbonylative Benzannulation

Abstract

We recently developed a novel Rh-catalyzed carbonylative benzannulation for the synthesis of indoles, benzofurans, and many related heterocycles. In this update, we demonstrated the utility of this method for the synthesis of several highly substituted benzofuran-containing natural products. The scope and limitation of the Rhcatalyzed carbonylative benzannulation was investigated in the context of natural product synthesis for the first time. This study also revealed the siteselectivity for Pd-catalyzed cross-coupling of substituted benzofurans. Two one-pot sequential crosscouplings were realized based on the observed siteselectivity. The strategy of preparing bicyclic heterocycles such as benzofurans by de novo synthesis of the benzene ring will find applications in many other related bioactive heterocycles.

Total synthesis of natural products containing benzofuran rings

“…The overall yields for 370 and 371 are 24.3% and 3.6%, respectively, starting form 363 (Scheme 80). 332 …”

“…332 The key step in their strategy was Rh-catalyzed carbonylative benzannulation methodology, which led to the formation of various highly substituted benzofurans present in natural products. This protocol started with market purchasable or readily accessible 2,3-dibromofuran 362.…”

Chiral Brønsted Acid‐Catalyzed Asymmetric 1,4‐Addition of Benzofuran‐Derived Azadienes with 3‐Substituted indoles

“…Benzofuran belongs to an important class of oxygenous heterocycles, which are found in natural products and bioactive compounds. [1] As a result, the synthesis of benzofuran derivatives has attracted much attention from the organic chemists. [2] Among different approaches, benzofuran-derived azadienes have recently been recognized as a class of versatile building blocks for the synthesis of benzofuran derivatives.…”

Application of Electrochemical Processes to Classical Iodocyclisation: Utility for Selectivity and Mechanistic Insight

“…Iodocyclisation of alkenes with oxygen nucleophiles is a powerful method of generating furan and benzofuran frameworks that maintain the iodine functionality and thereby allow further manipulation . The benzofuran motif is an important framework in a variety of natural products and drug substances and as such, rapid and efficient processes for the construction of substituted variants via the construction of the bicyclic nucleus are synthetically valuable . With our own research interests in practical electrochemical processes we here report an efficient route for the construction of the dihydrobenzofuran framework through an iodoetherification reaction of 2‐allylphenols where the molecular iodine and a Lewis acid are electrochemically generated from benign starting materials.…”

“…[1][2][3][4][5] The benzofuran motif is an important framework in a variety of natural products and drug substances and as such, rapid and efficient processes for the construction of substituted variants via the construction of the bicyclic nucleus are synthetically valuable. [6][7][8][9][10][11][12][13] With our own research interests in practical electrochemical processes we here report an efficient route for the construction of the dihydrobenzofuran framework through an iodoetherification reaction of 2-allylphenols where the molecular iodine and a Lewis acid are electrochemically generated from benign starting materials. Examples of iodocyclisation of phenols onto alkenes are conspicuously sparse in the literature with only a few examples being noted.…”