Copper‐Catalyzed Formylation of Amines by using Methanol as the C1 Source

Abstract

Cu/TEMPO catalyst systems are known for the selective transformation of alcohols to aldehydes, as well as for the simultaneous coupling of alcohols and amines to imines under oxidative conditions. In this study, such a Cu/TEMPO catalyst system is found to catalyze the N‐formylation of a variety of amines by initial oxidative activation of methanol as the carbonyl source via formaldehyde and formation of N,O‐hemiacetals and oxidation of the latter under very mild conditions. A vast range of amines, including aromatic and aliphatic, primary and secondary, and linear and cyclic amines are formylated under these conditions with good to excellent yields. Moreover, paraformaldehyde can be used instead of methanol for the N‐formylation.

An Environmentally Benign, Catalyst‐Free N−C Bond Cleavage/Formation of Primary, Secondary, and Tertiary Unactivated Amides

“…N‐(Quinolin‐8‐yl)formamide [17d] ( 3 c ): Using the experimental procedure EP‐1 , the product was obtained as brown solid in 68 % yield. A mixture of rotamers is observed; 1 H NMR (400 MHz, CDCl 3 ) δ 9.61 (br, s, 0.80H), 9.20 (br, s, 0.11H), 8.84 (t, J =18.7 Hz, 0.12H), 8.56 (d, J =4.1 Hz, 0.98H), 8.49 (dd, J =11.5, 7.0 Hz, 0.89H), 8.44 (s, 0.88H), 7.93 (d, J =8.3 Hz, 1.0H), 7.29–7.01 (m, 3.19H); 13 C NMR (100 MHz, CDCl 3 ) δ Major rotamer: 159.98, 144.41, 141.25, 125.41, 120.81, 117.92, 114.64, minor rotamer: 163.63, 146.67, 141.89, 124.54, 122.03, 119.06, 115.62.…”

A stable and recyclable Z-scheme g-C3N4/rGO/BiVO4 heterojunction photocatalyst for site-selective C-3 formylation of indoles with methanol as a formyl source under visible light

“…For example, methanol as a C1 source was used for the N -formylation of amines, but the transformation required a transition metal complex as the catalyst, such as a [Ru] complex, 22 a [Mn] complex, 23 an [Fe] complex, 24 and [Cu]/TEMPO. 25 The C-2 formylation of quinolines and quinoxalines with methanol was reported by using the catalytic system of TBHP/Fe(acac) 3 /AcOH. 26 Despite significant advances, the fly in the ointment was that these formylation reactions with methanol entirely required heating conditions and unrenewable transition metal catalysts or transition metal catalysts combined with oxidants in a homogeneous catalytic system.…”

In Situ‐Generated CuI Catalytic System for Oxidative N‐Formylation of N‐Heterocycles and Acyclic Amines with Methanol

“…b) Problems for the formylation of N‐heterocycles with methanol [34–43] . c) Formylation of THQ with methanol [44] . d) Direct catalytic coupling of N‐heterocycles with methanol (this work).…”

“…[9,[20][21][22][23][24][25][26][27][28][29][30][31] However, formylation of N-heterocycles with methanol as the formylation reagent is rare and still difficult to achieve, owing to the transformation of methanol into its oxidation state need to overcome higher stable thermodynamic energy than N-heterocycles, [32,33] which generally result in an unavoidable effect for N-heterocycles on account of its sensitive to many catalytic oxidation or dehydrogenation systems (Scheme 1b), [34][35][36][37][38][39][40][41][42][43] so that the only one literature available which reported copper-catalyzed N-formyla-tion of 1,2,3,4-tetrahydroquinoline (THQ) with methanol under aerobic conditions by Prechtl and co-workers (Scheme 1c). [44] Even so, this groundbreaking work provides important context for the development of a simpler, mild and highly selective catalytic system associated with CÀ N direct coupling of Nheterocycles with methanol.…”