A Novel Cascade Benzyne Nucleophilic Addition/Fries Rearrangement for Entry into 2,3-Disubstituted Phenols

Abstract

Materials and Methods. Unless stated otherwise, reactions were conducted in oven-dried glassware under an atmosphere of nitrogen using anhydrous solvents. THF was obtained from an Aldrich Sureseal bottle. Tetrabutylammonium difluorotriphenylsilicate was obtained from Aldrich. The following reagents and solvents were distilled prior to use: chlorotrimethylsilane (TMSCl), trimethylsilyl trifluoromethanesulfonate (TMSOTf), tetramethylenediamine (TMEDA), and heptane. Analytical thin-layer chromatography (TLC) was performed on precoated, glass-backed silica gel (Merck 60 F 254 ). Flash column chromatography was performed using an automated purification system (Teledyne Isco Combiflash® Rf). Pre-packed normal phase silica gel column was used for separation of products using Teledyne Isco RediSep® Rf High Performance Gold column. Microwave experiments were conducted with a Biotage® Initiator+ Microwave System equipped with a Robot Sixty sample changer. High resolution mass spectroscopy (HRMS) was performed on a Thermo Scientific LTQ Orbitrap Discovery instrument coupled with ESI. Nuclear magnetic resonance (NMR) spectra were recorded on a Bruker 400 MHz or 500 MHz spectrometer. Chemical shifts for 1 H NMR spectra are recorded in parts per million with the solvent resonance as the internal standard CHCl 3 (δ = 7.26 ppm) or DMSO (δ = 2.50 ppm). Data are reported as follows: chemical

o-Silylaryl Triflates: A Journey of Kobayashi Aryne Precursors

“…Mechanistically, a Smiles-type ipso substitution on intermediate 9-128 occurs to produce Meisenheimer complex 9-129 , which in turn undergoes an extrusion of SO 2 to produce biaryls 9-127 . In 2017, a nucleophilic addition-triggered Fries rearrangement on o -silylaryl triflates 9-130 was revealed by Bronner et al, giving rise to 2,3-disubstituted phenols 9-131 in moderate to high yields (Scheme c) …”

“…In 2017, a nucleophilic addition-triggered Fries rearrangement on osilylaryl triflates 9-130 was revealed by Bronner et al, giving rise to 2,3-disubstituted phenols 9-131 in moderate to high yields (Scheme 180c). 690 In 2018, Palakodety and co-workers demonstrated a basemediated cyclization of propargylic alcohols 9-132 with arynes, affording 3-benzofuranyl-2-oxindoles 9-133 along with the formation of 3-spirooxindole benzofurans 9-134 as minor products (Scheme 181). 691 692 An isocyanate intermediate 9-140 was proposed from the reaction of benzyne and acyl hydrazide 9-138, which could then react with alcohols to yield carbamates 9-139 (NuH = ROH) in modest to excellent yields.…”

Cascade Aryne Aminoarylation for Biaryl Phenol Synthesis

“…12 Further relevant prior art for the proposed aryne reactivity came from Bronner and co-workers, who described an aryne nucleophilic addition−Fries rearrangement system to access Cacylated amino-phenols 15 using sulfonamides as nucleophiles (Scheme 2C). 13 We began our studies using nosylate 8a, containing an electron-deficient arene, to promote the planned Smiles− Truce rearrangement. Sulfonate 8a can be prepared in three steps from a symmetrical resorcinol starting material, using a procedure modified from that of Hosoya and co-workers (see the Supporting Information).…”

“…An important precedent for sulfonate Smiles–Truce chemistry in the anionic regime has been reported by Quayle (Scheme B), who showed that silyl sulfonates 12 effectively undergo aryl transfer when treated with fluoride . Further relevant prior art for the proposed aryne reactivity came from Bronner and co-workers, who described an aryne nucleophilic addition–Fries rearrangement system to access C-acylated amino-phenols 15 using sulfonamides as nucleophiles (Scheme C) …”

“… 12 Further relevant prior art for the proposed aryne reactivity came from Bronner and co-workers, who described an aryne nucleophilic addition–Fries rearrangement system to access C-acylated amino-phenols 15 using sulfonamides as nucleophiles ( Scheme 2 C). 13 …”