Reductive Formylation Research Articles

First row transition metal catalyzed small molecule activation for sustainable organic transformation: Synergy between nature and chemist’s toolbox

In this review we have tried to present our view on the synergy between nature and chemists’ toolbox toward discovery of new reactions. Toward the search for new chemical reactivity, not only chemists learn from nature but nature’s evolutionary pathway perhaps has footprints of chemist’s innovative discoveries and beyond. Taking CO2 as a representative example of an abundant energy rich small molecule resource, we have tried to explore the probable strategies of activating the molecule using first row transition metal catalysts for sustainable organic transformation. Our study has tried to unfold nature’s strategy of CO2 activation and recycling which eventually motivated chemists toward discovery of new chemical reactions and further inspired to expand their toolbox for discovering new reactivities beyond the natural enzyme repertoire. The basic chemical CO2 activation strategy which have been focused in this review are using CO2 as a C1 building block in organic synthesis; catalytic reductive formylation and methylation of amines; carboxylation reactions via CO2 insertion. Additionally, carbonylation reactions with CO2 as CO surrogate has also been discussed. The focus of this review is to correlate nature’s chemical strategies with chemist’s approach to understand the concept involved in the chemical activation and utilization process of CO2 for unlocking new reaction paradigm, both for chemists’ and for nature’s catalytic repertoire.

Nickel-catalyzed reductive formylation of aryl halides via formyl radical

Aromatic aldehydes are the most fundamentally important compounds used in organic synthesis. The development of new synthetic methods for introduction of a formyl group into an organic scaffold is highly desirable. In this report, a nickel-catalyzed reductive coupling between aryl halides and α‑chloro N-methoxyphthalimide has been documented for the synthesis of a diverse array of aromatic aldehydes. Because of mild reductive coupling conditions, excellent functional group tolerance, especially for substrates containing free -OH and -NH2, was observed. Due to the simple operation mode, a large library of aromatic aldehydes can be quickly constructed by this process. Moreover, the present protocol is amenable for late-stage functionalization of bioactive compound. A combined computational and experimental investigation suggested the reaction may undergo a reaction mechanism of active Ni(I) catalyst formation and the formation of key formyl radical intermediate under zinc reductive conditions.

Supported gold nanoparticles on lignosulfonate coated magnetic nanoparticles: Investigation of its catalytic efficiency in the reductive formylation of nitroarenes

This article describes a biogenic synthesis towards the fabrication of Au NPs over sodium lignosulfonate (NaLS) modified Fe3O4 bio-nanocomposite and its catalytic and biological applications. The morphology and physicochemical characteristics of the material were determined over a number of analytical techniques like FT-IR, FE-SEM, TEM, EDS, XRD, ICP-OES and VSM. The prepared Fe3O4@NaLS/Au nanocomposite presented an excellent catalytic performance in the one-pot synthesis of N-formyl amines via reductive formylation of different nitrobenzene derivatives using NaBH4 as the hydride source and triethyl orthoformate [CH(OEt)3] as the formylating agent. Due to magnetic core, the nanocatalyst was retrieved magnetically with facile and recycled for 8 successive runs keeping its potential intact.

Silver-catalyzed Reductive Formylation of Amines with Carbon Dioxide

Silver-catalyzed Reductive Formylation of Amines with Carbon Dioxide

Use of Carbonyldiimidazole as an Activator of Formic Acid in a Tris(dibenzylideneacetone)dipalladium-Catalyzed Formylation of Aryl Iodides

AbstractA carbonyldiimidazole (CDI)-promoted generation of CO from formic acid has been exploited in a reductive formylation of aryl iodides in the presence of tris(dibenzylideneacetone)dipalladium. The reaction conditions are mild with a broad functional-group tolerance that includes keto, bromo, nitrile, ester, and nitro groups. In the reaction pathway, CDI reacts with formic acid to generate a formyl imidazole that ultimately produces the CO needed for the formylation process on the activated arylpalladium complex.

Palladium-Catalyzed Reductive Formylation of Aryl Iodides with CO2 under Mild Conditions.

A palladium-catalyzed reductive formylation of aryl iodides with carbon dioxide as the carbonyl source under mild reaction conditions was realized by using a combination of Pd(PCy3)2Cl2 and di-2-pyridyl ketone as the catalyst and phenylsilane as the reductive reagent, leading to a variety of aromatic aldehydes in moderate to excellent yields. The protocol features wide substrate scope, good functional group tolerance, and simple operation.

Cover Feature: Metal‐Free N‐Doped Carbon Catalyst Derived from Chitosan for Aqueous Formic Acid‐Mediated Selective Reductive Formylation of Quinoline and Nitroarenes (ChemSusChem 23/2022)

Cover Feature: Metal‐Free N‐Doped Carbon Catalyst Derived from Chitosan for Aqueous Formic Acid‐Mediated Selective Reductive Formylation of Quinoline and Nitroarenes (ChemSusChem 23/2022)

Homogeneous cobalt catalyzed reductive formylation of N-heteroarenes with formic acid

Herein, we report a cobalt N,N-bidentate complex catalyzed reductive formylation of N-heteroarenes for the generation of N-formyltetrahydroquinoline (FTHQ) derivatives, formic acid was employed as a transfer hydrogenation reagent that was safe, abundant and easy to handle. This work represented the first homogeneous system for reductive formylation of N-heteroarenes, the metal ligand cooperated dehydrogenation was the key to the success of this transformation. Deuteration labelling experiments and Hammet analysis were conducted and a plausible mechanism was suggested.

Metal-Free N-Doped Carbon Catalyst Derived from Chitosan for Aqueous Formic Acid-Mediated Selective Reductive Formylation of Quinoline and Nitroarenes.

A chitosan-derived metal-free N-doped carbon catalyst was synthesized and investigated for selective reductive formylation of quinoline to N-formyl-tetrahydroquinoline and nitroarenes to N-formyl anilides via aqueous formic acid (FA)-mediated catalytic transformation. FA dissociated on the catalyst surface and acted as a hydrogenating and formylating source for selective N-formylation of N-heteroarenes. The carbonized catalyst prepared at 700 °C offered the best activity. A 92 % yield of N-formyl-tetrahydroquinoline after 14 h and >99 % yield for N-formyl anilide after 12 h at 160 °C were obtained. The excellent catalytic activity was correlated with the type of "N" species and the basicity of the catalyst. Density functional theory calculations revealed that a water-assisted FA decomposition pathway (deprotonation and dehydroxylation) generated the surface adsorbed -H and -HCOO species, required for the formation of N-formylated products. In addition, the selective formation of N-formyl-tetrahydroquinoline and N-formyl anilides was explained by a comprehensive reaction energetics analysis.

Reductive Formylation of Nitroarenes using HCOOH over Bimetallic C−N Framework Derived from the Integration of MOF and COF

AbstractCoZn embedded C−N framework is prepared by the carbonization of CoZn containing MOF integrated with COF porous architecture in Ar atmosphere. The graphitic nature of porous carbon is confirmed from Raman analysis. The porosity and nanostructure information are retrieved from N2‐sorption and transmission electron microscopic analysis, respectively. The incorporation of different metals and their oxidation states and types of nitrogen present in the C−N framework are confirmed from X‐ray photoelectron spectroscopy. The basicity of the materials is determined from a CO2‐temperature programmed desorption. ZnCo embedded C−N framework exhibits excellent activity in the selective reductive formylation using HCOOH. For comparison, more than 15 materials are prepared, and their activities are compared. Several control experiments are performed to establish a structure‐activity relation. The recycling experiment, hot‐filtration test, and poisoning experiment demonstrate the metal embedded porous C−N framework‘s recyclability and stability. A reaction mechanism for the reductive N‐formylation of nitroaromatics is presented based on structure‐activity relationship, control reactions, and physicochemical characterizations. The development of interesting MOF‐COF‐derived metal nanoclusters embedded C−N framework for selective reductive formylation of nitroaromatics using formic acid will be highly attractive to catalysis researchers and industrialists.

Tetracoordinate borates as catalysts for reductive formylation of amines with carbon dioxide

The first example of borate-catalyzed N-formylation of amines using CO2 as the carbon source in the presence of hydrosilanes is demonstrated using sodium (trihydroxy)phenylborate as a transition metal-free catalyst.

UiO-66 as an efficient catalyst for N-formylation of amines with CO2 and dimethylamine borane as a reducing agent

The most effective way to make the best use of CO2, is the reductive formylation of amines, as formamides have many applications in industry. A new protocol has been developed for reductive N-formylation of amines with CO2 as a C1 carbon source and DMAB (Dimethylamine borane) as a reducing agent in the presence of Zr-containing metal–organic framework (MOF) as an efficient, heterogeneous recyclable catalyst. We used UiO-66 and UiO-66-NH2 as catalysts for N-formylation of amines and observed that both the catalyst performs equally. Therefore, we continued our studies with UiO-66 as a catalyst. The UiO-66 MOF shows good catalytic activity and affording the desired formamides in good to excellent yield. This catalytic system is very efficient for several amines including primary and secondary aliphatic cyclic and aromatic amines. Moreover, the prepared catalyst was recycled up to four recycled without a considerable decrease in catalytic activity.

One-pot photocalalytic reductive formylation of nitroarenes via multielectron transfer by carbon nitride in functional eutectic medium

In the past years organic semiconductor photocatalysis has made the remarkable advances in developing efficient synthetic chemical routes to well refined structures. Until now, most efforts were focused on optimizing of the semiconductor photocatalyst, while solvents were largely ignored. Herein, we design a series of functional deep eutectic solvents (DES) with adjustable physicochemical properties – density, viscosity, glass transition temperature, and chemical activity towards reductive formylation of nitroarenes. The DES are prepared from abundant, sustainable resources, which makes them an affordable alternative to the ionic liquids, even on larger industrial scales. By combining the ammonium formate-based DES with carbon nitride photocatalyst, we enable the simultaneous six-electron reduction of nitro-compounds to the corresponding N-substituted formamides and benzimidazoles in one pot.

1 H-1,2,3-Triazol-5-ylidenes: Readily Available Mesoionic Carbenes.

Classical carbenes are usually described as neutral compounds featuring a divalent carbon with only six electrons in their valence shell. It was only in 1988 that our group prepared the first isolable example, in which the carbene center was stabilized by a push-pull effect, using a phosphino and a silyl substituent. In the last 30 years, a myriad of acyclic and cyclic push-pull and push-push carbenes, bearing different heteroatom substituents, have been isolated. Among them, the so-called N-heterocyclic carbenes (NHCs), which include cyclic (alkyl)(amino)carbenes (CAACs), are arguably the most popular. They have found a vast number of applications ranging from catalysis to material science, and even in medicine. In this Account, we focus on the synthesis, structure, electronic properties, coordination, and applications of a different class of stable cyclic carbenes, namely, 1 H-1,2,3-triazol-5-ylidenes. In contrast with NHCs and CAACs, these compounds have no reasonable canonical resonance forms that can be drawn showing a carbene without additional charges. According to the IUPAC, they belong to the family of mesoionic compounds and thus they are named mesoionic carbenes (MICs). In 2010, we prepared the first stable 1,2,3-triazol-5-ylidene, via a CuAAC reaction, followed by alkylation of the resulting 1,2,3-triazole, and deprotonation. Later, we synthesized more robust N3-arylated counterparts from 1,3-diarylated-1 H-1,2,3-triazolium salts. Both synthetic routes can be carried out in multigram scales, making these MICS readily available. Importantly, MICs do not dimerize which contrasts with NHCs that can give the corresponding Wanzlick-type olefin. This property leads to relaxed steric requirements for their isolation; even C-unsubstituted MICs can be stored for months in the solid state at room temperature. The practicality and easily scalable syntheses of MICs allow for the preparation of polycarbenes, such as bis(1,2,3-triazol-5-ylidenes) (i-bitz), the analogues of the well-known 2,2'-bipyridines (bpy). MIC-transition metal complexes are excellent precatalysts for variety of chemical transformations, which include hydrohydrazination of alkynes, olefin metathesis, reductive formylation of amines with carbon dioxide and diphenylsilane, hydrogenation and dehydrogenation of N-heteroarenes in water, cycloisomerization of enynes, asymmetric Suzuki-Miyaura cross-coupling, and water oxidation (WO) reactions. Besides their catalytic applications, MIC-transition metal complexes have found applications in material sciences as exemplified by the preparation of the first iron(III) complex that is luminescent at room temperature. The peculiar properties of mesoionic triazolylidenes, combined with their enhanced stability, position them as excellent candidates to address some current challenges such as access to high-oxidation-state 3d metal complexes, the stabilization of highly reactive main group elements, the stabilization of nanoparticles, the preparation of efficient catalysts and photosensitizers based on earth-abundant transition metals, and the functionalization of self-assembled monolayers (SAMs) on gold.

Rhodium-Catalyzed Formylation of Aryl Halides with CO2 and H2.

The reductive formylation of aryl iodides/bromides to aryl aldehydes using CO2/H2 is presented for the first time. It was realized over a catalytic system composed of RhI3 or RhI3/Pd(dppp)Cl2 (dppp = 1,3-bis(diphenyphosphino)propane) and PPh3 in the presence of Ac2O/Et3N at 100 °C, affording aromatic aldehydes in good to excellent yields, together with good functional-group tolerance and broad substrate scope. The reaction proceeds through three cascade steps, involving HCOOH formation, CO release, and formylation of aryl halides.

Reductive formylation of amines with CO2 using sodium borohydride: A catalyst-free route

Using sodium borohydride (NaBH4) as the reducing reagent, the reductive fomylation of amines with CO2 was realized at 100°C under catalyst-free conditions, and a series of formylated products were obtained in excellent yields. The reaction mechanism investigation demonstrated that NaBH4 could react with CO2 to form intermediate, which further reacted with amines, producing the formylated compounds. It was indicated that three hydrogen atoms from NaBH4 could involve in the reductive formylation, and therefore only 0.5 equiv. NaBH4 relative to the substrate was enough for getting high product yields. In addition, NaBH4 was also very efficient for the reductive cyclization of o-phenylenediamine with CO2 to synthesize benzimidazoles. NaBH4 as an efficient reducing reagent for the CO2-involed reductive reactions may have promising applications.

A photoactive bimetallic framework for direct aminoformylation of nitroarenes

A bimetallic catalyst, AgPd@g-C3N4, on graphitic carbon nitride enables the concerted reductive formylation of aromatic nitro compounds under photo-chemical conditions; formic acid serves the dual role of a hydrogen source and a formylating agent.

ChemInform Abstract: Effective Formylation of Amines with Carbon Dioxide and Diphenylsilane Catalyzed by Chelating bis(tzNHC) Rhodium Complexes.

AbstractThe shown rhodium complex (TZNHC) is the best catalyst for the reductive formylation reaction of amines with CO2 and Ph2SiH2.

ChemInform Abstract: Heterogeneous Gold‐Catalyzed Selective Reductive Transformation of Quinolines with Formic Acid.

AbstractDepending on conditions (solvent system, temperature), either site‐selective reduction or regioselective reductive formylation of quinolines and isoquinoline can be achieved using rutil‐supported gold nanoparticles.

Effective Formylation of Amines with Carbon Dioxide and Diphenylsilane Catalyzed by Chelating bis(tzNHC) Rhodium Complexes

AbstractThe reductive formylation of amines using CO2 and hydrosilanes is an attractive method for incorporating CO2 into valuable organic compounds. However, previous systems required either high catalyst loadings or high temperatures to achieve high efficiency, and the substrate scope was mostly limited to simple amines. To address these problems, a series of alkyl bridged chelating bis(NHC) rhodium complexes (NHC=N‐heterocyclic carbene) have been synthesized and applied to the reductive formylation of amines using CO2 and Ph2SiH2. A rhodium‐based bis(tzNHC) complex (tz=1,2,3‐triazol‐5‐ylidene) was identified to be highly effective at a low catalyst loading and ambient temperature, and a wide substrate scope, including amines with reducible functional groups, were compatible.