Bridging lab and industry with flow electrochemistry

A revitalization of organic electrosynthesis has incited the organic chemistry community to adopt electrochemistry as a green and cost-efficient method for activating small molecules to replace highly toxic and expensive redox chemicals. However, many of the critical challenges of batch electrosynthesis, especially for organic synthesis, still remain. The combination of continuous flow technology and electrochemistry is a potent means to enable industry to implement large scale electrosynthesis. Indeed, flow electrosynthesis helps overcome problems that mainly arise from macro batch electro-organic systems, such as mass transfer, ohmic drop, and selectivity, but this is still far from being a flawless and generic applicable process. As a result, a notable increase in research on methodology and hardware sophistication has emerged, and many hitherto uncharted chemistries have been achieved. To better help the commercialization of wide-scale electrification of organic synthesis, we highlight in this perspective the advances made in large-scale flow electrosynthesis and its future trajectory while pointing out the main challenges and key improvements of current methodologies

Iron(II)-catalyzed enantioselective meso-epoxide-opening with anilines

A highly enantioselective method for the catalytic opening of aromatic meso-epoxides with aniline derivatives was developed. The desired chiral ß-amino alcohols were obtained in mostly good to very good yields with excellent enantioselectivities. Structural evidence of the pre-catalyst revealed a scarcely disclosed heptadentate Fe(II) complex with the chiral bipyridine ligan

Atom economical synthesis of N-alkylbenzamides via iron(III) sulfate catalyzed rearrangement of 2-alkyl-3-aryloxaziridines in water and in the presence of surfactant

A green and mild synthetic route to N-alkylbenzamides involves eco-friendly one pot synthesis of 2-alkyl-3-aryloxaziridines from N-alkylamines and benzaldehydes followed by iron(III) sulfate catalyzed rearrangement to the corresponding amides in water as solvent and in the presence of sodium dodecyl sulfate as surfactant. This green approach affords N-alkylbenzamides in high overall yields under simple and minimum manipulation

Fe(BF4)2 catalyzed inter- and intramolecular carbonyl-ene reaction of trifluoropyruvate

Inter- and intramolecular carbonyl-ene reactions have been developed using 5 mol% Fe(BF4)2 as catalyst, affording homoallylic alcohols in 36–87% isolated yields. This catalyst, prepared from FeCl2 and AgBF4, is the first FeII Lewis acid reported for the carbonyl-ene reaction using ethyl trifluoropyruvate. The method was successfully applied to the reaction of various 1,1-disubstituted alkenes with ethyl trifluoropyruvate and to the cyclization of citronellal

Iron bis(oxazoline) complexes in asymmetric catalysis

Asymmetric reactions catalyzed by iron complexes have attracted considerable attention because iron is a ubiquitous, inexpensive, and environmentally benign metal. Various chiral iron complexes can be prepared from bis IJ oxazoline) ligands and be used in asymmetric reactions. This overview charts the development and application of chiral iron bis IJ oxazoline) and pyridine-2,6-bis IJ oxazoline) catalysts through their most prominent and innovative uses in asymmetric catalysis, especially in Lewis acid and oxidation catalysis

New trends in bismuth-catalyzed synthetic transformations

This review covers uses of bismuth catalysts since 2005 with a special emphasis on the emerging applications of such catalysts. Low toxicity, low catalytic loading, synergistic effects with other catalysts, and some hydrocompatibility properties confer to bismuth salts major advantages. The expanding activity in the field clearly highlights the growing potential of bismuth catalysts. The article is not a comprehensive review on bismuth catalysis but a selection of its most promising uses in challenging synthetic transformation

Enantioselective aromatic sulfide oxidation and tandem kinetic resolution using aqueous H2O2 and chiral iron Bis(oxazolinyl)bipyridine catalysts

An efficient method for the oxidation of aromatic sulfides was developed using aqueous H2O2 catalyzed by in situ-generated chiral Fe/6,6'-bis(oxazolinyl)-2,2'-bipyridine (bipybox) complex. The corresponding sulfoxides were obtained in high enantio-selectivities (up to 98.5:1.5 er) and good yields (up to 61%) when the mono-oxidation of the sulfides was performed in combination with the kinetic resolution of the sulfoxide into the sulfone

The power of iron catalysis in diazo chemistry

The use of iron catalysis to enable reactions with diazo compounds has emerged as a valuable tool to forge carbon–carbon or carbon–heteroatom bonds. While diazo compounds are often encountered with toxic and expensive metal catalysts, such as Rh, Ru, Pd, Ir, and Cu, a resurgence of Fe catalysis has been observed. This short review will showcase and highlight the recent advancements in iron-mediated reactions of diazo compounds

Iron- and bismuth-catalyzed asymmetric Mukaiyama aldol reactions in aqueous media

We have developed asymmetric Mukaiyama aldol reactions of silicon enolates with aldehydes catalyzed by chiral Fe II and Bi III complexes. Although previous reactions often required relatively harsh conditions, such as strictly anhydrous conditions, very low temperatures (-78 C), etc., the reactions reported herein proceeded in the presence of water at 0 C. To find appropriate chiral water-compatible Lewis acids for the Mukaiyama aldol reaction, many Lewis acids were screened in combination with chiral bipyridine L1, which had previously been found to be a suitable chiral ligand in aqueous media. Three types of chiral catalysts that consisted of a Fe II or Bi III metal salt, a chiral ligand (L1), and an additive have been discovered and a wide variety of substrates (silicon enolates and aldehydes) reacted to afford the desired aldol products in high yields with high diastereo- and enantioselectivities through an appro- priate selection of one of the three catalytic systems. Mechanistic studies elucidated the coordination environments around the Fe II and Bi III centers and the effect of additives on the chiral catalysis. Notably, both Brønsted acids and bases worked as efficient additives in the Fe II-catalyzed reactions. The assumed catalytic cycle and transition states indicated important roles of water in these efficient asymmetric Mukaiyama aldol reactions in aqueous media with the broadly applicable and versatile catalytic systems

Fe(OTf)2-catalyzed thia-Michael addition reaction : a green synthetic approach to β-thioethers

A convenient Fe(OTf)2‐catalyzed Michael addition reaction of thiols to α,β‐unsaturated carbonyl compounds was developed. The use of a simple procedure (EtOH, room temperature, air atmosphere) allowed to set up effective green catalytic conditions for the C‐S bond formation. The scope of the reaction was demonstrated using various substituted thiols and original Michael acceptors. The corresponding β‐thioethers were obtained in good to excellent yields (up to 99%). Also, the derivatization into the one‐pot thia‐Michael addition/oxidation reaction of 3‐(3‐(phenylthio)butanoyl)oxazolidin‐2‐one using H2O2 has proven to be efficient