Copper(I)‐Catalyzed Asymmetric Dearomatization of Indole Acetamides with 3‐Indolylphenyliodonium Salts

Abstract

The rapid and direct asymmetric synthesis of 3-(3a-indolyl)hexahydropyrroloindoline motifs is an extremely important part of the total synthesis of several alkaloid structures. Herein, an intermolecular, asymmetric cascade dearomatization reaction of indole acetamides with 3-indolylphenyliodonium salts has been developed. This protocol provides a straightforward access to 3-(3a-indolyl)hexahydropyrroloindolines bearing an all-carbon quaternary stereocenter at the C3 position of the indoline ring with high enantioselectivities. The utility of the protocol has been demonstrated by the formal asymmetric synthesis of folicanthine.

Catalytic Asymmetric Dearomatization by Transition-Metal Catalysis: A Method for Transformations of Aromatic Compounds

“…Cu-Catalyzed Dearomatization of Indoles via Cross-Coupling with Iodonium Salts Originally reported by the MacMillan group, 74 the Reisman group, 75,76 and the You group. 77 varied positions of both reaction partners are well tolerated. This chemistry of 3-indolylphenyliodonium salts is unique because it represents a rare umpolung of the originally highly nucleophilic reactivity of the C3 position of indoles.…”

“…77 The reactions between 3-indolyl-acetamides 113 and 114 are promoted by a Cu complex supported by a chiral BOX ligand L22, leading to the desired dearomatized products 115 in reasonable yields with excellent enantioselectivity. Different substituents at Scheme 24.…”

Indole‐ and Pyrrole‐BX: Bench‐Stable Hypervalent Iodine Reagents for Heterocycle Umpolung

“…[9] There is only one report on the use of indole iodonium salts involving a transition metal: the coppercatalyzed de-aromatization of indoles reported by You and coworkers. [11] This stands in stark contrast with the hundreds of transformations reported for other aryl iodonium salts, [6] and is probably due to the lower stability of indole and pyrrole iodonium salts in presence of metals and/or at higher temperature. The enhanced stability of cyclic hypervalent iodine reagents, in particular those obtained from 2-iodobenzoic acid and its derivatives -the benzidoxol(on)es -has been established since several decades (Scheme 1B).…”

Recent Advances in the Catalytic Functionalization of “Electrophilic” Indoles

“…A significant advancement in the field was brought by You and coworkers with the synthesis of 3‐indolylphenyliodonium salts 52 and their consequent employment as electrophilic arylating agents in the enantioselective synthesis of pyrroloindolines 54 . The combination of chiral bis‐oxazoline ligand 53 (11 mol%) and [Cu(CH 3 CN) 4 ]PF 6 (10 mol%) triggers the cascade dearomative protocol of C(3)‐indole acetamides 51 in high yield and ee up to 99% (Scheme ).…”