Expedient Access to Indolyl-Substituted Tri- and Diarylmethanes and (±)-Colletotryptin E by Silica Sulfuric Acid Catalyzed Transindolylation

Abstract

An expedient access to a series of nonsymmetrical bis(indolyl)methanes (BIMs) through transindolylation of readily available symmetrical 3,3′-BIMs with various indoles catalyzed by silica-supported sulfuric acid has been established. This approach not only provides a useful strategy for the synthesis of structurally diverse BIMs, but also provides examples of nucleophilic substitution of BIMs with aromatic and nonaromatic π-systems, leading to a library of indolyl-substituted tri- and diarylmethanes. Moreover, this method was successfully applied in the first total synthesis of the 2,3′-BIM alkaloid (±)-colletotryptin E in three steps with an overall yield of 46%. The features of this procedure include a metal-free process, an inexpensive and environmentally friendly catalyst, mild reaction conditions, broad functional-group tolerance, good yields, and gram-scalable preparations.

Short Total Synthesis of (+)-Colletotryptins B-D and Mucronatin B Derivative

“…Based on our experimental results and information in the literature, − a plausible mechanism for the formation of synthetic (+)-colletotryptin B ( 2 ) and ent -colletotryptin A ( 13 ) is illustrated in Scheme . In the presence of Lewis acid Bi­(III) salts, activation of ( S )- 11 with a bismuth catalyst involves interaction with the ipso position of the C-3 indole ring, yielding species A .…”

“…To date, most reported methods focus on synthesizing 2,3′-bis­(indolyl)­methanes (BIMs) with aryl and/or methyl side chains via acid-catalyzed indolylation of aryl indole-2-methanol or 2-vinyl indoles, including asymmetric synthesis (Scheme A,B). − However, many of these methods have limitations regarding substrate preparation, requiring an aryl side chain on the substrates. − Recently, a novel strategy for synthesizing 2,3′-BIMs via acid-catalyzed transindolylation of readily available 3,3′-BIMs has emerged. , This strategy was exemplified by the rapid total synthesis of (±)-gelliusine E, along with its 2,3′-bis­(indoyl)­ethylamine analogues (Scheme C) . Nonetheless, the development of a stereoselective transindolylation reaction leading to the construction of optically active 3-(indol-2-yl)-3-(indol-3-yl)-1,2-propanediol, bearing two stereogenic centers, has not been reported and remains a significant challenge.…”