Enantioselective Synthesis of Tetrahydropyrano[3,4‐b]indoles: Palladium(II)‐Catalyzed Aminopalladation/1,4‐Addition Sequence

Abstract

An ovel palladium(II)-catalyzed cyclization of aniline-tethered alkynyl cyclohexadienones is reported. This reaction offers an atom-economical and redox-neutral access to various cyclohexenone-fused tetrahydropyrano [3,4b]indoles with high yield and excellent enantioselectivity. Remarkably,t his work represents the first example on at ransition-metal-catalyzed asymmetric intramolecular aminopalladation/1,4 addition sequence. Scheme 1. Methodsf or the synthesis of 1, 3,4,9-tetrahydropyrano-[3,4b]indoles.

Rh(III)-Catalyzed Asymmetric Synthesis of Axially Chiral Biindolyls by Merging C–H Activation and Nucleophilic Cyclization

“…In fact, intramolecular couplings have been adopted to suppress this simple cyclization. 10 In addition, subsequent cyclometalation of C is less feasible because it is coordinatively saturated with respect to a concerted metalation−deprotonation pathway. 11 This calls for judicious design of a catalytic system that orchestrates the reactivity of these two substrates.…”

Synthesis of Indoles via Intermolecular and Intramolecular Cyclization by Using Palladium-Based Catalysts

“…At low temperatures and in the absence of water or HOAc, the reaction did not go well and negative effects on the yields were observed. Except for substrate (115), all other starting substrates afforded the dried product good to excellent yields despite the electronic or steric crowding rendered by the substitutions present in the cyclohexadienone or benzene ring; even trifluoromethyl and bromide substituents were well tolerated in the methodology [174]. The cyclohexanone-fused tetrahydropyrano [3,4-b]indoles (114) was synthesized by intramolecular Pd(OAc) 2 -catalyzed cyclization of the aniline-tethered alkynyl cyclohexadienones (113) using a ligand and bipyridine in the mixture of solvents of DMF/H 2 O/HOAc (Scheme 35).…”

“…At low temperatures and in the absence of water or HOAc, the reaction did not go well and negative effects on the yields were observed. Except for substrate (115), all other starting substrates afforded the dried product good to excellent yields despite the electronic or steric crowding rendered by the substitutions present in the cyclohexadienone or benzene ring; even trifluoromethyl and bromide substituents were well tolerated in the methodology [174]. In 2007, Tang and co-workers utilized PdX 2 and CuX (X = Chloro, Bromo) in the synthesis of 2-substituted 3-halo-1H-indoles (124) via the annulation of 2-ethynyl benzeneamines (123) (Scheme 37).…”

“…The success of this reaction was the insertion step of isonitrile. The presence of H 2 O is key for the formation of 3-amidylindoles (174). Not only R 2 CN, but also cyclohexyl isonitriles were tolerated in the reaction and produced 3-cyanated indole [186].…”

Copper(I)-catalyzed diastereo- and enantio-selective construction of optically pure exocyclic allenes

“…Inspired by recent progress in the copper(I)-catalyzed asymmetric transformations of 1,3-enynes to functional chiral allenes and our continuous interest in catalytic asymmetric desymmetrization of cyclohexadienone derivatives [38][39][40][41][42][43][44][45][46][47][48] , we envisioned that the key axially chiral allenylcopper intermediate T1, generated from the chemo-, regio-, and enantio-selective insertion of 1,3enyne to chiral copper hydride species, would be rapidly trapped by the intramolecular enones to yield the desired chiral exocyclic allenes 2 with hopefully high enantioselectivity and diastereoselectivity ( Fig. 2d).…”