Brønsted Acid-Catalyzed Intramolecular Hydroarylation of β-Benzylstyrenes

Abstract

Using triphenylmethylium tetrakis(pentafluorophenyl)borate as a convenient Brønsted acid precatalyst, β-(α,α-dimethylbenzyl)styrenes are shown to cyclize efficiently to afford a variety of new indanes that possess a benzylic quaternary center. The geminal dimethyl-containing quaternary center is proposed to be necessary to arm the substrate for cyclization through steric biasing.

[Pd]‐Catalyzed Intermolecular Coupling and Acid Mediated Intramolecular Cyclodehydration: One‐Pot Synthesis of Indenes

“…As the carbon tether is devoid of gem‐dialkyl group and could not push the olefin to come close to the aromatic ring to facilitate the cyclization to give indane. Indeed, these results are in good agreement with that reported by Stokes et al that signify the impact of a gem‐dialkyl moiety on the synthesis of indanes. Gratifyingly, this protocol is advantageous because it facilitates the synthesis of benzyl styrenes in a highly regioselective manner (i.e.…”

Dispersion-Controlled Regioselective Acid-Catalyzed Intramolecular Hydroindolation of cis-Methindolylstyrenes To Access Tetrahydrobenzo[cd]indoles

“…Substrate conformational biasing arising from steric constraints, such as those imposed by geminal dialkyl groups (i.e., the Thorpe–Ingold effect), are often used to circumvent energetic barriers to bond formation in order to prepare new and useful molecules. We recently developed an intramolecular acid-catalyzed hydroarylation of β-(α ′ ,α ′ -dialkyl)­benzylstyrenes ( A , Scheme A), showing that a gem -dialkyl group can be used to synthesize indanes efficiently ( B ). , We became interested in applying this design concept to more complex and medicinally relevant substrates, namely 4-bromoindole-derived β-(α′,α′-dimethyl)-4′-methindolylstyrenes like C (Scheme B), which are rapidly prepared by sequential enolate cross-coupling, Wittig, and benzyl protection reactions . Cyclization could occur at either C3 to afford tetrahydrobenzo­[ cd ]­indole D or at C5 to afford tetrahydrocyclopenta­[ e ]­indole E .…”

“…We recently developed an intramolecular acid-catalyzed hydroarylation of β-(α′,α′dialkyl)benzylstyrenes (A, Scheme 1A), showing that a gemdialkyl group can be used to synthesize indanes efficiently (B). 2,3 We became interested in applying this design concept to more complex and medicinally relevant substrates, namely 4-bromoindole-derived β-(α′,α′-dimethyl)-4′-methindolylstyrenes like C (Scheme 1B), which are rapidly prepared by sequential enolate cross-coupling, Wittig, and benzyl protection reactions. 4 Cyclization could occur at either C3 to afford tetrahydrobenzo [cd]indole D or at C5 to afford tetrahydrocyclopenta[e]indole E. Herein, we report that a variety of 3-aryl-5,5-dimethyl-1,3,4,5-tetrahydrobenzo[cd]indoles (D) are efficiently prepared in good yield by treating the cis-configured isomer of C with Brønsted acid catalysts (Scheme 1B, top pathway).…”

Directedortho-Metalation and Anionicortho-Fries Rearrangement of Polycyclic AromaticO-Carbamates: Regioselective Synthesis of Substituted Chrysenes

“…The products were purified by flash chromatography using silica gel (particle size 40−60 μm, 60 Å) with PE or heptane and EtOAc. 1 H and 13 C NMR spectra were either recorded on Bruker Avance 300 or 400 MHz spectrometers with chemical shifts reported in ppm relative to internal TMS (δ = 0), CHCl 3 (δ = 7.26), or CDCl 3 (δ = 77.0). The multiplicities were recorded as singlet, s; doublet, d; triplet t; double doublet, dd; doublet of triplet, dt; triplet of doublet, td; quartet, q; multiplet, m; apparent, app; broad, br.…”

“…9 In the medicinal area, substituted chrysenes have been found to possess anticancer activity due to their intercalation with DNA 10 and have been shown to inhibit the functioning of topoisomerase II, a potentially advantageous property for cancer chemotherapy. 11 Traditional synthetic approaches to PAHs involve a multitude of Lewis and Brønsted acid catalyzed S E Ar reactions, 12,13 in which the Friedel−Craft acylation plays a major role. 14 Recently, new methodologies based on cooperative catalysis, 15 radical substitution, 16 and, significantly, transition-metal-catalyzed C−H activation 17 have been developed.…”