Studies on Iron-Catalyzed Aerobic Oxidation of Benzylic Alcohols to Carboxylic Acids

Abstract

A comprehensive study on aerobic oxidation of benzylic alcohols­ to carboxylic acids with a catalytic amount each of Fe(NO3)3·9H2O, TEMPO, and KCl is conducted. Various synthetically useful functional groups are well tolerated in the reaction. Distinct electronic and steric effects are observed in the reaction: electron-withdrawing groups accelerate the reaction while electron-donating groups make the reaction slower, and ortho-substituted substrates react slower than meta-substituted substrates. Several large-scale reactions (100 mmol) are conducted using a slow air flow of 30 mL/min to demonstrate the practicality of this method in an academic laboratory.

Iron nitrate and 4-OH-TEMPO-cocatalyzed aerobic oxidation of isochromans

“…15 Oxygen plays an important role in regenerating NO 2 by oxidizing NO. 12 The presence of peroxide intermediates cannot be excluded: radical 1a′ could react with O 2 to afford peroxyl radical species Int 4 , which could be further transformed to afford lactone 2a . 6 b ,7…”

“…Iron-based catalysis has received much attention because of its natural abundance, low cost and environmentally friendly nature (Scheme 1b): 11 Xiao and coworkers reported Fe(OTf) 2 with a PyBisulidine ligand with low conversion with 1,1′-oxidi-isochromans as the byproducts; 11 a in 2017, Shen et al . successfully applied Fe(NO 3 ) 3 ·9H 2 O with KPF 6 for the aerobic oxidation of isochromans in MeCN at 80 °C; 11 b later, this transformation was also realized at 80 °C by Feng and He via the incorporation of dppf with disulfide; 11 c herein, based on our early reports with Fe(NO 3 ) 3 ·9H 2 O catalysis, 11 d ,12 we wish to report our recent observation that with the help of 4-OH-TEMPO, the Fe(NO 3 ) 3 ·9H 2 O catalyzed aerobic oxidation of isochromans could be realized in high yields under very mild conditions of rt (Scheme 1c).…”

[Cp*RhCl2]2catalyzed three-component coupling cyclization of 2,3-allenoic acids with 2,3-allenols in the presence of Cu(OAc)2·H2O

“…Subsequent one-pot reduction with NaBH 4 afforded 1,3-diol 10 in 56% yield. 10 The hemiacetal unit in 9 may also be oxidized by Fe/TEMPO 11 to afford the potentially useful yet difficult to prepare stained β-lactone 11 12,13 in 64% yield.…”

Iron-catalyzed aerobic oxidation of silyl ethers to carboxylic acids

“…Reactions in DCM, DCE, or toluene at room temperature for 21 hours hardly or did not give octanoic acid 2a (Table 1, entries 1–3). 7 To our delight, the reaction in MeCN or DME gave 82% or 22% NMR yield, respectively (Table 1, entries 4 and 5). The formation of 2a in 88% NMR yield was detected when using THF as the solvent (Table 1, entry 6).…”