Construction of N-Aryl-Substituted Pyrrolidines by Successive Reductive Amination of Diketones via Transfer Hydrogenation.

N-aryl-substituted pyrrolidines are important moieties widely found in bioactive substances and drugs. Herein, we present a practical reductive amination of diketones with anilines for the synthesis of N-aryl-substituted pyrrolidines in good to excellent yields. In this process, the N-aryl-substituted pyrrolidines were furnished via successive reductive amination of diketones via iridium-catalyzed transfer hydrogenation. The scale-up performance, water as a solvent, simple operation, as well as derivation of drug molecules showcased the potential application in organic synthesis.

Iridium-catalysed reductive allylic amination of α,ß-unsaturated aldehydes.

Allylic amination is a powerful tool for constructing N-allylic amines widely found in bioactive molecules. Generally, allylic alcohols and unsaturated hydrocarbons have been considered for allylic amination reactions to minimize waste production. Herein, we present an iridium-catalysed method for reductive allylic amination of α,ß-unsaturated aldehydes with amines to afford N-allylic amines under air conditions. This protocol is demonstrated to provide products from many substrates (41 examples) in moderate-to-excellent yields. This synthetic methodology is also highlighted by the synthesis of drug molecules, optically pure products, as well as scale-up experiments.

One-pot reductive amination of carbonyl compounds and nitro compounds via Ir-catalyzed transfer hydrogenation.

The formation of C-N bond is a vital synthetic tool for establishing molecular diversity, which is highly sought after in a wide range of biologically active natural products and drugs. Herein, we present a new strategy for the synthesis of secondary amines via iridium-catalyzed one-pot reductive amination of carbonyl compounds with nitro compounds. This method is demonstrated for a variety of carbonyl compounds, including miscellaneous aldehydes and ketones, which are compatible with this catalytic system, and deliver the desired products in good yields under mild conditions. In this protocol, the reduction of nitro compounds occurs in situ first, followed by reductive amination to form amine products, providing a new one-pot procedure for amine synthesis.

Recent advances of Cp*Ir complexes for transfer hydrogenation: focus on formic acid/formate as hydrogen donors.

Transfer hydrogenation reactions offer synthetically powerful strategies to deliver various hydrogenated compounds with the advantages of efficiency, atom economy, and practicability. On one hand, formic acid/formate function as promising hydrogen sources owing to their readily obtainable, inexpensive, and easy to handle nature. On the other hand, Cp*Ir complexes show high activities in transfer hydrogenation. This review highlights progress achieved for transfer hydrogenation of CO, CC, and CN bonds of a variety of unsaturated substrates, as well as amides focusing on Cp*Ir complexes as catalysts and formic acid/formate as hydrogen sources.

Furan-2-yl Anions as γ-Oxo/Hydroxyl Acyl Anion Equivalents Enabled by Iridium-Catalyzed Chemoselective Reduction.

The last piece of the puzzle: Furan-2-yl anions are first demonstrated as robust γ-oxo and γ-hydroxyl acyl anion equivalents to convert aldehydes and ketones into trifunctionalized dihydroxyl ketones and hydroxyl diones through sequential nucleophilic addition, Achmatowicz rearrangement, and herein freshly established iridium-catalyzed highly selective transfer hydrogenation reduction.

Access to Saturated Oxygen Heterocycles and Lactones via Electrochemical Sulfonylative Oxycyclization of Alkenes with Sulfonyl Hydrazides.

A facile electrochemical sulfonylative cycloetherification of linear unsaturated alcohols with sulfonyl hydrazides under mild conditions has been accomplished. This catalyst- and oxidant-free protocol proceeds via electro-oxidation, followed by radical addition, as well as an intramolecular oxygen nucleophilic process. This methodology is compatible with a broad substrate scope and good functional group compatibility, which provides a valuable and convenient synthetic tool for the synthesis of saturated five-, six-, seven-, and eight-membered ring oxygen heterocycles. Furthermore, sulfonylative cycloesterification of linear unsaturated acids toward the lactone products has also been established under this electrochemical system. In addition, control experiments indicated that the N-H bonds of the sulfonyl hydrazide molecule are non-essential.

Cyclometalated iridium complexes-catalyzed acceptorless dehydrogenative coupling reaction: construction of quinoline derivatives and evaluation of their antimicrobial activities.

The acceptorless dehydrogenative coupling (ADC) reaction is an efficient method for synthesizing quinoline and its derivatives. In this paper, various substituted quinolines were synthesized from 2-aminobenzyl alcohols and aryl/heteroaryl/alkyl secondary alcohols in one pot via a cyclometalated iridium-catalyzed ADC reaction. This method has some advantages, such as easy availability of raw materials, mild reaction conditions, wide range of substrates, and environmental friendliness which conforms to the principles of green chemistry. Furthermore, a gram-scale experiment with low catalyst loading offers the potential to access the aryl/heteroaryl quinolones in suitable amounts. In addition, the antibacterial and antifungal activities of the synthesized quinolines were evaluated in vitro, and the experimental results showed that the antibacterial activities of compounds 3ab, 3ad, and 3ah against Gram-positive bacteria and compound 3ck against C. albicans were better than the reference drug norfloxacin.

Synthesis of N-alkoxy amines and hydroxylamines via the iridium-catalyzed transfer hydrogenation of oximes.

Cationic iridium (Ir) complexes were found to catalyze the transfer hydrogenation of oximes to access N-alkoxy amines and hydroxylamines, and the reaction was accelerated by trifluoroacetic acid. The practical application of this protocol was demonstrated by a gram-scale transformation and two-step synthesis of the fungicide furmecyclox (BAS 389F) in overall yields of 92 and 85%, respectively. An asymmetric protocol using chiral Ir complexes to afford chiral N-alkoxy amines was demonstrated, but the low yields/ee obtained indicated that further development was required.

Ru-Catalyzed Asymmetric Addition of Arylboronic Acids to Aliphatic Aldehydes via P-Chiral Monophosphorous Ligands.

Chiral alcohols are among the most widely applied in fine chemicals, pharmaceuticals and agrochemicals. Herein, the Ru-monophosphine catalyst formed in situ was found to promote an enantioselective addition of aliphatic aldehydes with arylboronic acids, delivering the chiral alcohols in excellent yields and enantioselectivities and exhibiting a broad scope of aliphatic aldehydes and arylboronic acids. The enantioselectivities are highly dependent on the monophosphorous ligands. The utility of this asymmetric synthetic method was showcased by a large-scale transformation.

Selective Synthesis of Ketones and Chiral Allylic Alcohols from the Addition of Arylboronic Acids to α,ß-Unsaturated Aldehydes Mediated by a Transition Metal/Monophosphorus Ligand System.

Here, we demonstrated a transition metal-mediated/monophosphorus ligand system for the selective synthesis of ketones or chiral allylic alcohols in high yields/enantiomeric excess from the 1,2-addition of arylboronic acids to α,ß-unsaturated aldehydes. Notably, isomerization of the chiral allylic alcohols to ketones was suppressed by the Ru-catalyzed/monophosphorus ligand system. The asymmetric catalytic system provides an alternative and efficient method of preparing chiral allylic alcohols.

Photoinduced radical cascade cyclization of acetylenic acid esters with oxime esters to access cyanalkylated coumarins.

A photoinduced radical cascade cyclization of acetylenic acid esters with oxime esters is described, providing cyanalkylated coumarins in superior yields under mild conditions. Radical capture and luminescence quenching experiments showed that this transformation was accomplished via a radical addition/5-exo spirocyclization/1,2-ester migration process.

Iridium-catalyzed reductive etherification of α,ß-unsaturated ketones and aldehydes with alcohols.

An iridium complex-catalyzed reductive etherification of α,ß-unsaturated ketones and aldehydes with primary alcohols is presented, affording allyl ethers in excellent yields. Deuterated and control experiments showed that this etherification transformation proceeded through a cascade transfer hydrogenation and alcohol condensation process. Moreover, the utility of this protocol is evidenced by the gram-scale performance.

pH-Mediated Selective Synthesis of N-Allylic Alkylation or N-Alkylation Amines with Allylic Alcohols via an Iridium Catalyst in Water.

Amination of allylic alcohols is an effective approach in the facile synthesis of N-allylic alkylation or N-alkylation amines. Recently, a series of catalysts were devised to push forward this transformation. However, current synthetic methods are typically limited to achieve either N-allylic alkylation or N-alkylation products via a certain catalyst. In this article, a pH-mediated selective synthesis of N-allylic alkylation or N-alkylation amines with allylic alcohols via an iridium catalyst with water as the environmental benign solvent is revealed, enabling the miscellaneous synthesis of N-allylic alkylation and N-alkylation products in outstanding yields. Furthermore, a gram-scale experiment with low catalyst loading offers the potential to access a distinct entry for the synthesis of the antifungal drug naftifine.

Iridium Complex-Catalyzed Transfer Hydrogenation of N-Heteroarenes and Tentative Asymmetric Synthesis.

An iridium-catalyzed transfer hydrogenation of N-heteroarenes to access a series of substituted 1,2,3,4-tetrahydroquinoline derivatives in excellent yields is disclosed. This transformation is distinguished with water-soluble and air-stable iridium complexes as the catalyst, formic acid as the hydrogen source, mild reaction conditions, and broad functional group compatibility. Most importantly, a tentative chiral N,N-chelated Cp*Ir(III) complex-catalyzed enantioselective transfer hydrogenation is also presented, affording chiral products in excellent yields and good enantioselectivities.

Substrate-Controlled Cu(OAc)2-Catalyzed Stereoselective Semi-Reduction of Alkynes with MeOH as the Hydrogen Source.

A substrate-controlled stereoselective semi-reduction of alkynes with MeOH as the hydrogen source has been developed, and readily available Cu(OAc)2 (copper acetate) is utilized as an optimal catalyst. The detailed investigation of the mechanism revealed distinct catalytic processes for the (Z)- and (E)-alkenes, respectively. As a result, a diversity of alkynes (including terminal, internal alkynes etc.) were compatible under the mild reaction conditions. Furthermore, the high proportion of deuterium in Z-alkenes (up to 96%) was obtained using d 4-methanol as a solvent.

Amide Iridium Complexes As Catalysts for Transfer Hydrogenation Reduction of N-sulfonylimine.

Sulfonamide moieties widely exist in natural products, biologically active substance, and pharmaceuticals. Here, an efficient water-soluble amide iridium complexes-catalyzed transfer hydrogenation reduction of N-sulfonylimine is developed, which can be carried out under environmentally friendly conditions, affording a series of sulfonamide compounds in excellent yields (96-98%). In comparison with organic solvents, water is shown to be critical for a high catalytic transfer hydrogenation reduction in which the catalyst loading can be as low as 0.001 mol %. These amide iridium complexes are easy to synthesize, one structure of which was determined by single-crystal X-ray diffraction. This protocol gives an operationally simple, practical, and environmentally friendly strategy for synthesis of sulfonamide compounds.

Cyclometalated Iridium Complex-Catalyzed N-Alkylation of Amines with Alcohols via Borrowing Hydrogen in Aqueous Media.

This paper develops a methodology for cyclometalated iridium complex-catalyzed N-alkylation of amines with alcohols via borrowing hydrogen in the aqueous phase. The cyclometalated iridium catalyst-mediated N-alkylation of amines with alcohols displays high activity (S/C up to 10,000 and yield up to 96%) and ratio of amine/imine (up to >99:1) in a broad range of substrates (up to 46 examples) using water as the green and eco-friendly solvent. Most importantly, this transformation is simple, efficient, and can be performed at a gram scale, showcasing its potential for industrially synthesizing N-alkylamine compounds.

Highly Catalytic Enantioselective Reformatsky Reaction with Aldehydes and Ketones Using an Available Prolinol Ligand.

A highly Me2Zn-mediated catalytic enantioselective Reformatsky reaction of aldehydes and ketones with ethyl iodoacetate using a readily available prolinol ligand is reported. This reaction provides an efficient method for the construction of ß-hydroxy esters in up to 98% yield and 95% enantiomeric excess (ee) value. A wide range of functional groups are tolerated and the practicality of this protocol is demonstrated by performing the reaction on a gram scale.

Recent advances in the oxime-participating synthesis of isoxazolines.

Isoxazoline compounds are used as important intermediates for the synthesis of organic molecules, which are widely used in the chemical and life science industries. Oxime-participating cyclization has emerged as an efficient strategy for the construction of isoxazolines. This review is devoted to highlighting the main achievements (since 2010) in the development of methodologies for the synthesis of isoxazolines. According to the reaction mechanism, the oxime-participating synthesis of isoxazolines can be mainly classified into four reaction types: iminoxyl radical-initiated intramolecular cyclization, intermolecular radical addition-initiated cyclization, intramolecular nucleophilic cyclization, and [3 + 2] cycloaddition. Meanwhile, miscellaneous examples are also illustrated, such as [2 + 2 + 1] cycloaddition. Representative reactions will be discussed for each of the highlighted synthetic strategies. In addition, the enantioselective synthesis of isoxazolines is also illustrated in this review.

Photoredox-Catalyzed Oxy-/Aminofluoroalkylative Cyclization of Alkenes.

Here we describe a photoredox-catalyzed oxy-/aminofluoroalkylative cyclization of alkenes for coupling available Rf-I reagents to generate fluoroalkylated 2,3-dihydrobenzofuran and indolin derivatives with good to excellent yields under mild conditions. A wide range of functional groups are tolerated. The mechanistic investigation of radical trapping and cyclic voltammetry experiments proposed that a radical/SET (single electron transfer) pathway proceeded in this reaction.