Intermediate‐Dependent Unusual [4+3], [3+2] and Cascade Reactions of 3‐Indolylmethanols: Controllable Chemodivergent and Stereoselective Synthesis of Diverse Indole Derivatives

Chemodivergent and stereoselective construction of indole‐containing scaffolds, as well as synthesis of diverse indole derivatives, has long been a goal in the chemistry community. In this work, we reveal key intermediate‐dependent unusual 4+3], 3+2] and cascade reactions of 3‐indolylmethanols with Nazarov reagents, leading to controllable chemodivergent and stereoselective synthesis of diverse indole derivatives. (i) In the presence of hydrobromic acid in acetonitrile, 3‐indolylmethanols performed an electronically reversed 4+3] cyclization with Nazarov reagents, thus constructing a cycloheptab]indole framework with the concomitant creation of an all‐carbon seven‐membered ring bearing a quaternary stereocenter in a highly diastereoselective fashion. (ii) Under the promotion of hydrobromic acid in fluorobenzene, methyl‐protected 3‐indolylmethanols underwent site‐selective 3+2] cyclization with Nazarov reagents, which built up a cyclopentab]indole skeleton bearing a spiro‐quaternary stereocenter in high chemical yields. (iii) By changing the acid to trifluoromethanesulfonic acid in acetonitrile, the same reactants carried out a cascade reaction to afford the corresponding indole derivatives by generating multiple new C C bonds in an (E/Z)‐selective mode. Based on control experiments, these reactions were found to be dependent on the formation of a key type of intermediate, which underwent a variety of unusual transformations including C C bond cleavage and reassembly under different reaction conditions to afford diverse indole derivatives. These unusual reactions not only for the first time establish several challenging new transformations of 3‐indolylmethanols with precise control of chemo‐, diastereo‐ and (E/Z)‐selectivity, but also provide efficient methods for constructing indole‐containing scaffolds in a stereoselective and chemodivergent manner.