Iodide as a Nucleophilic Trigger in Aryne Three-Component Coupling for the Synthesis of 2-Iodobenzyl Alcohols

Abstract

The synthetic potential of KI as the iodide source in aryne three-component coupling has been demonstrated using aldehydes as the third component. This mild and transition-metal-free coupling reaction allowed the straightforward synthesis of 2-iodobenzyl alcohols in moderate to good yields with good functional group compatibility. Moreover, KBr and KCl could be used as the nucleophilic trigger in this aryne multicomponent coupling (MCC) and N-methylisatin and CO2 could be used as the electrophilic third components.

Poly(ethylene glycol) Dimethyl Ethers (PEGDME): Efficient and Recyclable Solvents for Aryne-Involved Reactions

“…Thus, the reaction with 4-nitrobenzaldehyde 13 with potassium iodide under optimized conditions of PEGDME and KF gave 2iodobenzyl alcohol analogue 15 in 62% yield (Scheme 3a). 16 A three-component aminoselenation of aryne 2 using N,Ndimethyl aniline 16 and phenyl selenium bromide 17 gave 2aminophenyl selenium analogue 18 in 75% yield (Scheme 3b). 17 1,2-Aminohalogination of arynes with N,N-dimethyl aniline 16 and CCl4 in PEGDME resulted 20 in 96% yield (Scheme 3c).…”

“…mp = 96−98 °C. (2-Iodophenyl)(4-nitrophenyl)methanol (15) 16 General procedure A: 4-Nitrobenzaldehyde (150 mg, 0.99 mmol, 1.0 equiv. ), potassium iodide (412 mg, 2.48 mmol, 2.5 equiv.…”

“…Thus, the reaction of 4-nitrobenzaldehyde (13) with potassium iodide under the optimized conditions (PEGDME and KF) gave 2-iodobenzyl alcohol analogue 15 in 62% yield (Scheme 3a). 16 A three-component aminoselenation of aryne 2 using N,N-dimethylaniline (16) and phenyl selenium bromide (17) gave 2-aminophenyl selenium ana-…”

Engaging Isatins in Multicomponent Reactions (MCRs) – Easy Access to Structural Diversity

“…Recently, 3‐hydroxy‐3‐(2‐iodophenyl)‐1‐methyloxindole was prepared via a aryne three‐component coupling, using KI as the iodide source and nucleophilic trigger of the reaction, and N ‐methylisatin as the electrophilic component. The generation of the aryne was promoted by KF/18‐crown‐6 in heated THF (Scheme 122C) [244] …”

Selective Synthesis of N-H and N-Aryl Benzotriazoles by the [3 + 2] Annulation of Sodium Azide with Arynes

“…14 We have recently demonstrated the aryne multicomponent coupling 15 triggered by KI for the synthesis of 2-iodobenzyl alcohols using aldehydes as the third component. 16,17 Inspired by the use of inorganic halides as the nucleophilic trigger in aryne reactions, the present study was initiated by the treatment of aryne generated from the triflate precursor 1a using CsF and 18-crown-6 with excess of NaN 3 in CH 3 CN solvent. Interestingly, under these conditions, the N-H benzotriazole product 2a was isolated in 32% yield ( entry 1).…”