Brønsted Acid Catalyzed (4 + 2) Cyclocondensation of 3-Substituted Indoles with Donor–Acceptor Cyclopropanes

Abstract

Acylcyclopropanes are employed as useful donor− acceptor cyclopropanes that undergo formal (4 + 2) cyclocondensation with N-unprotected 3-substituted indoles in the presence of a Brønsted acid catalyst. The reaction involves the simultaneous alkylation of both the N and C-2 positions of the indole and provides access to the 8,9-dihydropyrido[1,2-a]indole scaffold that is the central core of several biologically relevant indole alkaloids in excellent yields and good selectivities.

Cascade Ring-Opening/Cyclization Reaction of Spiro(nitrocyclopropane)oxindoles with Huisgen Zwitterions and Synthesis of Pyrazolo[3,4-b]indoles

“…Donor–acceptor (D–A) cyclopropanes have emerged as versatile building blocks in the syntheses of a variety of carbocycles and heterocycles . Their unique and diverse reactivity in organic synthesis may be attributed to the push–pull effect of vicinal electron-donor and electron-acceptor substituents and inherent high ring strain of the cyclopropane backbone as well.…”

Expedient Ni(OTf)2/visible light photoredox-catalyzed annulation of donor–acceptor cyclopropanes with cyclic secondary amines

“…1 The combination of the high ring strain (27.5 kcal mol −1 ) 2 and vicinal DA motifs has led to a variety of synthetic transformations, paving the way to constructing carbo- and heterocycles. 3–5 On the other hand, the cross-dehydrogenative coupling (CDC) of C–H bonds affords a potential synthetic tool to C–C bond formation under oxidative conditions. These reactions have made considerable progress using transition-metals such as Pd and Rh to activate the C–H bond and a stoichiometric amount of peroxo-compounds as the oxidant to complete the catalytic cycle.…”

Bi-Catalyzed 1,2-Reactivity of Spirocyclopropyl Oxindoles with Dithianediol: Access to Spiroheterocycles

“…However, specific substitution patterns, including the installation of donor and acceptor (DA) moieties on vicinal positions, lead to heterolytic cleavage of the C–C bond in the presence of either heat or a Lewis acid and provide pivotal driving force to generate 1,3-dipolar species (Scheme ). The effective stabilization of the zwitterionic intermediate has elucidated their complete exploration as the basic feedstock for various rearrangement, ring-opening, and [3+ n ]-cycloaddition reactions to access densely functionalized architectures . In this vein, the ring enlargement of oxindole-derived DA spirocyclopropanes has attracted a substantial amount of attention in recent years owing to the abundance of the oxindole core in potent pharmacophore moieties (Figure ).…”

“…Compound 3a was re-isolated with exclusive trans selectivity, and no epimerization was observed, which might be due to the relative thermodynamic preference of the trans isomer . In accordance with the experimental results and literature studies on the Lewis acid-catalyzed annulation of DA cyclopropanes, chelation of Bi­(OTf) 3 with the carbonyl moiety of oxindole 1 can give I that can lead to the regioselective ring cleavage of cyclopropane to furnish II by stabilizing the negative charge (Scheme ). Subsequent rearrangement via a 1,2-hydride shift can generate stable 1,2-dipolar complex III .…”