Efficient Copper-Catalyzed Trifluoromethylation of Aromatic and Heteroaromatic Iodides: The Beneficial Anchoring Effect of Borates

Abstract

Efficient copper-catalyzed trifluoromethylation of aromatic iodides was achieved with TMSCF 3 in the presence of trimethoxyborane. The Lewis acid was used to anchor the in situ generated trifluoromethyl anion and suppress its rapid decomposition. Broad applicability of the new trifluoromethylating reaction was demonstrated in the functionalization of different aromatic and heteroaromatic iodides.

Synthesis of a 3′-C-ethynyl-β-d-ribofuranose purine nucleoside library: Discovery of C7-deazapurine analogs as potent antiproliferative nucleosides

“…This led us to assign the structure of the trifluoromethylated compound prepared using Langlois' reagent as the C8 (C6) regio-isomer. The C7 (C5) substituted heterocycle 42 could be obtained from the known C7 (C5) iodide 40 [34] by subsequent N-Boc protection and trifluoromethylation using the Ruppert reagent [37] (the N-Boc protecting group was lost during the reaction). Comparison of the 1 H NMR spectra of both regioisomers 39 and 42 (see Supporting Information) led to the confirmation that 39 and thus also 48, are the C8 (C6) substituted isomers.…”

Copper-Catalyzed Trifluoromethylation of Alkoxypyridine Derivatives

“…With the iodo compounds in hand, we studied their reactivity in copper-catalyzed trifluoromethylation reaction, utilizing the literature procedure developed earlier in our laboratories for the functionalization of aryl iodides [ 24 ]. These included heating a mixture of one equivalent of the aryl iodide, 20 mol% copper iodide, 20 mol% phenanthroline, three equivalents of potassium fluoride, three equivalents of trimethyl borate, and three equivalents of trimethylsilyl-trifluoromethane under argon in dimethyl sulfoxide at 60 °C.…”

“…There are multiple approaches for the establishment of the trifluoromethyl group, including nucleophilic, radical, and electrophilic routes [ 10 , 11 , 12 , 13 , 14 , 15 , 16 , 17 , 18 , 19 , 20 , 21 , 22 , 23 ]. Our objective was to systematically study the copper-catalyzed trifluoromethylation [ 24 ] of alkoxypyridine derivatives and their benzologs that could serve as useful building blocks in medicinal chemistry.…”

Palladium catalyzed chloroethoxylation of aromatic and heteroaromatic chlorides: an orthogonal functionalization of a chloroethoxy linker

“…To illustrate the applicability of this method, we carried out the synthesis of an analog and an intermediate of active pharmaceutical ingredients (Scheme 5) containing condensed heterocyclic cores such as indoles and benzothiophenes. First, we prepared the aryl-chloride substrate 5a through the Nbenzylation of indole with 4-chlorobenzyl-bromide, 14 for the key aminoalkoxylation step. Then the palladium-catalyzed coupling reaction with Na[B(OCH 2 CH 2 Cl) 4 ] and subsequent amination under the developed reaction conditions led to a 70% yield of the desired product 5b, which contains the core of the selective estrogen receptor modulator (SERM) drug,…”