A Remote ‘Imidazole’‐Based Ruthenium(II) Para‐Cymene Pre‐catalyst for the Selective Oxidation Reaction of Alkyl Arenes and Alcohols

Herein we disclosed the use of a remote ‘imidazole’‐based precatalyst [(para‐cymene)Ru^II(L)Cl]⁺, C‐1 where L=2‐(4‐substituted‐phenyl)‐1H‐imidazo[4,5‐f]^[1,10] phenanthroline) for the selective oxidation of a variety of alkyl arenes/heteroarenes and alcohols to their corresponding aldehydes or ketones in presence of tert‐butyl hydroperoxide (TBHP). The remote ‘imidazole’ moiety present in the complex facilitates the activation of oxidant and subsequent generation of active species via the release of para‐cymene from C‐1 , which in‐turn was less effective without the ‘imidazole’ moiety. The mechanistic features of C‐1 promoted oxidation of alkyl arenes were also assessed from spectroscopic, kinetic, and few control experiments. The substrate scope for C‐1 promoted oxidation reaction was assessed based on the selective oxidation of 27‐different alkyl arenes/heteroarenes and 25 different alcohols to their corresponding aldehydes/ketones in moderate to good yields.     

Iron‐Catalyzed Direct Oxidative Alkylation and Hydroxylation of Indolin‐2‐ones with Alkyl‐Substituted N‐Heteroarenes

Presented herein is the first direct alkylation and hydroxylation reaction between two different C(sp³)?H bonds, indolin‐2‐ones and alkyl‐substituted N‐heteroarenes, through an oxidative cross‐coupling reaction. The reaction is catalyzed by a simple iron salt under mild ligand‐free and base‐free conditions. The reaction is environmentally benign, employs air (molecular oxygen) as the terminal oxidant and oxygen source for the synthesis of O‐containing compounds, and produces only water as the byproduct.     

Imidazolin‐2‐ylidenaminophosphines as Highly Electron‐Rich Ligands for Transition‐Metal Catalysts

A variety of chemical transformations benefit from the use of strong electron‐donating ancillary ligands, such as alkylphosphines or N‐heterocyclic carbenes when electron‐rich metal centers are required. Herein, we describe a facile and highly modular access to monodentate and bidentate imidazolin‐2‐ylidenamino‐substituted phosphines. Evaluation of the phosphine’s electronic properties substantiate that the formal replacement of alkyl or aryl groups by imidazolin‐2‐ylidenamino groups dramatically enhance their donor ability beyond that of alkylphosphines and even N‐heterocyclic carbenes. The new phosphines have been coordinated onto palladium(II) centers, and the beneficial effect of the novel substitution patterns has been explored by using the corresponding complexes in the palladium‐catalyzed Suzuki–Miyaura cross‐coupling reaction of non‐activated aryl chloride substrates.     

Direct Regiospecific and Highly Enantioselective Intermolecular α‐Allylic Alkylation of Aldehydes by a Combination of Transition‐Metal and Chiral Amine Catalysts

The first direct intermolecular regiospecific and highly enantioselective α‐allylic alkylation of linear aldehydes by a combination of achiral bench‐stable Pd⁰ complexes and simple chiral amines as co‐catalysts is disclosed. The co‐catalytic asymmetric chemoselective and regiospecific α‐allylic alkylation reaction is linked in tandem with in situ reduction to give the corresponding 2‐alkyl alcohols with high enantiomeric ratios (up to 98:2 e.r.; e.r.=enantiomeric ratio). It is also an expeditious entry to valuable 2‐alkyl substituted hemiacetals, 2‐alkyl‐butane‐1,4‐diols, and amines. The concise co‐catalytic asymmetric total syntheses of biologically active natural products (e.g., Arundic acid) are disclosed.     

Enantio‐ and Diastereoselective 1,2‐Additions to α‐Ketoesters with Diborylmethane and Substituted 1,1‐Diborylalkanes

The catalytic enantioselective synthesis of boronate‐substituted tertiary alcohols through additions of diborylmethane and substituted 1,1‐diborylalkanes to α‐ketoesters is reported. The reactions are catalyzed by readily available chiral phosphine/copper(I) complexes and produce β‐hydroxyboronates containing up to two contiguous stereogenic centers in up to 99:1 e.r. and greater than 20:1 d.r. The utility of the organoboron products is demonstrated through several chemoselective functionalizations. Evidence indicates the reactions occur via an enantioenriched α‐boryl‐copper‐alkyl intermediate.     

Metal‐Free I2‐Catalyzed Highly Selective Dehydrogenative Coupling of Alcohols and Cyclohexenones

The I₂ catalyzed highly selective oxidative condensation of cyclohexenones and alcohols for the synthesis of aryl alkyl ethers has been described. DMSO is employed as the mild terminal oxidant. This novel methodology offers a metal‐free reaction condition, operational simplicity and broad substrate scope to afford valuable products from inexpensive reagents. Various meta‐substituted aromatic ethers which are hardly synthesized from the reported methods requiring meta‐substituted phenols, are efficiently prepared by the present protocol.     

Chromium‐Catalyzed Alkylation of Amines by Alcohols

The alkylation of amines by alcohols is a broadly applicable, sustainable, and selective method for the synthesis of alkyl amines, which are important bulk and fine chemicals, pharmaceuticals, and agrochemicals. We show that Cr complexes can catalyze this C?N bond formation reaction. We synthesized and isolated 35 examples of alkylated amines, including 13 previously undisclosed products, and the use of amino alcohols as alkylating agents was demonstrated. The catalyst tolerates numerous functional groups, including hydrogenation‐sensitive examples. Compared to many other alcohol‐based amine alkylation methods, where a stoichiometric amount of base is required, our Cr‐based catalyst system gives yields higher than 90 % for various alkyl amines with a catalytic amount of base. Our study indicates that Cr complexes can catalyze borrowing hydrogen or hydrogen autotransfer reactions and could thus be an alternative to Fe, Co, and Mn, or noble metals in (de)hydrogenation catalysis.     

Manganese‐Catalyzed Direct Olefination of Methyl‐Substituted Heteroarenes with Primary Alcohols

Herein, we present the first catalytic direct olefination of methyl‐substituted heteroarenes with primary alcohols through an acceptorless dehydrogenative coupling. The reaction is catalyzed by a complex of the earth‐abundant transition metal manganese that is stabilized by a bench‐stable NNN pincer ligand derived from 2‐hydrazinylpyridine. The reaction is environmentally benign, producing only hydrogen and water as byproducts. A large number of E‐disubstituted olefins were selectively obtained with high efficiency.     

Kinetic Resolution of Tertiary 2‐Alkoxycarboxamido‐Substituted Allylic Alcohols by Chiral Phosphoric Acid Catalyzed Intramolecular Transesterification

A highly enantioselective kinetic resolution of tertiary 2‐alkoxycarboxamido allylic alcohols has been achieved through a chiral phosphoric acid catalyzed intramolecular transesterification reaction. Both alkyl,aryl‐ and dialkyl‐substituted tertiary allylic alcohols were resolved with excellent efficiencies, affording both the recovered tertiary alcohols and the carbamate products with high enantioselectivities (with s factors up to 164.6). A gram‐scale reaction with 1 mol % catalyst loading and the facile conversion of the enantioenriched products into useful chiral building blocks, such as chiral oxazolidinones and β‐amino alcohols, demonstrate the value of this reaction.     

Direct N‐Methylation Reaction Using DMSO as One‐Carbon Bridge: Convenient Access to Heterocycle‐Containing β‐Amino Ketones

A novel oxidative C? S bond cleavage reaction of DMSO for dual C? C and C? N bond formation is described. A series of acetyl heteroarenes could be selectively converted into the corresponding β‐amino ketones, which are frequently found in biologically active compounds and pharmaceuticals. DMSO acted in this reaction not only as the solvent but also as a one‐carbon bridge.     

Tertiary α‐Silyl Alcohols by Diastereoselective Coupling of 1,3‐Dienes and Acylsilanes Initiated by Enantioselective Copper‐Catalyzed Borylation

An efficient synthesis of functionalized tertiary α‐silyl alcohols by an enantio‐ and diastereoselective copper‐catalyzed three‐component coupling of 1,3‐dienes, bis(pinacolato)diboron, and acylsilanes is reported. The reaction proceeds well with different 1,3‐dienes and a broad range of aryl‐ as well as alkenyl‐ but also alkyl‐substituted acylsilanes. The target compounds are formed with high regio‐, diastereo‐, and enantioselectivity (up to 99 % ee and d.r. >20:1) and are highly versatile synthetic building blocks.     

Copper‐Catalyzed Remote C(sp3)−H Trifluoromethylation of Carboxamides and Sulfonamides

Reported herein is an unprecedented protocol for trifluoromethylation of unactivated aliphatic C(sp³)?H bonds. With Cu(OTf)₂ as the catalyst, the reaction of N‐fluoro‐substituted carboxamides (or sulfonamides) with Zn(CF₃)₂ complexes provides the corresponding δ‐trifluoromethylated carboxamides (or sulfonamides) in satisfactory yields under mild reaction conditions. A radical mechanism involving 1,5‐hydrogen atom transfer of N‐radicals followed by CF₃‐transfer from Cu^II?CF₃ complexes to the thus formed alkyl radicals is proposed.     

Visible Light‐Induced Room‐Temperature Heck Reaction of Functionalized Alkyl Halides with Vinyl Arenes/Heteroarenes

The first visible light‐induced Pd‐catalyzed Heck reaction of α‐heteroatom substituted alkyl iodides and ‐bromides with vinyl arenes/heteroarenes has been developed. This transformation efficiently proceeds at room temperature and enables synthesis of valuable functionalized allylic systems, such as allylic silanes, boronates, germanes, stannanes, pivalates, phosphonates, phthalimides, and tosylates from the corresponding α‐substituted methyl iodides. Notably, synthesis of the latter substrates failed under existing thermally induced Pd‐catalyzed conditions, which highlights the importance of visible light for this transformation.     

Synthesis of Some Novel Class of Regioselective Spiro Isoxazolidine Derivatives via 1,3‐Dipolar Cycloaddition Reaction of N‐Benzyl‐C‐fluoro‐substituted Phenyl Nitrones in Ionic Liquid

Synthesis of some new class of regioselective spiro isoxazolidine derivatives have been described using N‐benzyl‐C‐fluoro substituted‐phenyl nitrones with new dipolarophiles via 1,3‐dipolar cycloaddition reaction in ionic liquid. The novel spiro cycloadducts found to exhibit good synthetic potentiality as they could be converted into synthetically more important spiro 1,3‐amino alcohols. Simple reaction methodology, noninvolvent of catalysts, good to excellent yields, and greener approaches are the important features noticed in this syntheses.     

The synthesis of novel acetolactate synthase inhibitors,N‐(asymmetrically disubstituted phosphoryl)‐N′‐(4,6‐dimethoxypyrimidin‐2‐yl) ureas

In view of the isosterism of the sulfonyl group(‐SO₂‐) and the phosphoryl group, two new types of compounds N‐(N‐aryl‐O‐alkyl phosphoryl)‐N′‐(4,6‐dimethoxypyrimidin‐2‐yl) ureas (2) and N‐(N‐aryl‐N‐alkylphosphoryl)‐N′‐(4,6‐dimethoxypyrimidin‐2‐yl) ureas (3) were designed and synthesized by treating N‐(arylaminochlorophosphoryl)‐N′‐(4,6‐dimethoxypy‐rimidinyl‐2‐) ureas (4) with alcohols or amines. Compounds 4 were obtained by treating dichloro‐phosphoryl isocyanate with 4,6‐dimethoxy‐2‐amino‐pyrimidine and then with aromatic amines. The enzyme tests in vitro indicated that compounds 2 and 3 were two novel classes of acetolactate synthase (ALS) inhibitors and also showed that phosphoryl groups[‐P(O)(OR)‐, R=alkyl] and [‐P(O)(NHR), R=alkyl] were likely to be good bioisosteres of the sulfonyl group (‐SO₂‐) in the sulfonylureas. © 1999 John Wiley & Sons, Inc. Heteroatom Chem 10:237–241, 1999     

Visible‐Light‐Driven Palladium‐Catalyzed Radical Alkylation of C−H Bonds with Unactivated Alkyl Bromides

Reported herein is a novel visible‐light photoredox system with Pd(PPh₃)₄ as the sole catalyst for the realization of the first direct cross‐coupling of C(sp³)−H bonds in N‐aryl tetrahydroisoquinolines with unactivated alkyl bromides. Moreover, intra‐ and intermolecular alkylations of heteroarenes were also developed under mild reaction conditions. A variety of tertiary, secondary, and primary alkyl bromides undergo reaction to generate C(sp³)−C(sp³) and C(sp²)−C(sp³) bonds in moderate to excellent yields. These redox‐neutral reactions feature broad substrate scope (>60 examples), good functional‐group tolerance, and facile generation of quaternary centers. Mechanistic studies indicate that the simple palladium complex acts as the visible‐light photocatalyst and radicals are involved in the process.     

Rational Design,Green Synthesis,and Initial Evaluation of a Series of Full‐Color Tunable Fluorescent Dyes Enabled by the Copper‐Catalyzed N‐Arylation of 6‐Phenyl Pyridazinones and Their Application in Cell Imaging

There is widespread interest in the application, optimization, and evolution of the transition‐metal‐catalyzed arylation of N‐heteroarenes to discover full‐color tunable fluorescent core frameworks. Inspired by the versatile roles of pyridazinone in organic synthesis and medicinal chemistry, herein, we report a simple and efficient copper‐catalyzed cross‐coupling reaction for the N‐functionalization of pyridazinones in neat water. To achieve the efficient conversion of pyridazinones and organic halides in aqueous phase, a series of copper‐salen complexes composed of different Schiff base ligands were investigated by rational design. A final choice of fine‐tuned hydrophilicity balanced with lipophilicity among the candidates was confirmed, which affords excellent activity towards the reaction of a wide range of pyridazinones and organic halides. More importantly, the products as N‐substituted pyridazinones were synthesized rationally by this methodology as full‐color tunable fluorescent agents (426–612 nm). The N2 position of pyridazinones was modified by different aryl group such as benzothiazole, N,N‐dimethylaniline, 3‐quinoline, 4‐isoquinoline and 2‐thiophene, resulting in a series of full‐color tunable fluorescent reagents. Meanwhile, the effects of electron‐donating and electron‐withdrawing groups of the 6‐substituted phenyl ring have also been investigated to optimize the fluorescent properties. These fluorescent core frameworks were studied in several cell lines as fluorescent dyes. Different colors from blue to red were observed by using fluorescence microscopy and confocal microscopy.     

Chelation‐Driven Rearrangement of Primary Alkyl Aminopalladation Products to Stable Trisubstituted Alkyl–Palladium Complexes

The formation of highly substituted carbon centers using catalysis has been a widely sought after goal, but complexes of highly substituted carbon atoms with transition metals are rare, and the factors that affect the relative stability of complexes with differentially substituted carbon atoms are poorly understood. In this study, a set of equilibrating alkyl–palladium complexes were subtly tuned to form either a primary or trisubstituted alkyl complex as the more thermodynamically favored state, depending on either the substrate or reaction conditions. An X‐ray crystal structure of the trisubstituted alkyl–palladium complex is presented and compared with the corresponding primary alkyl complex. The mechanism for rearrangement and the factors that drive the change in stability are discussed.     

Copper‐Catalyzed Aerobic Oxidations of 3‐N‐Hydoxyaminoprop‐1‐ynes to Form 3‐Substituted 3‐Amino‐2‐en‐1‐ones: Oxidative Mannich Reactions with a Skeletal Rearrangement

Cu‐catalyzed aerobic oxidations of readily available 3‐N‐hydroxyaminopro‐1‐ynes with water, alcohols, or thiols to form diverse 3‐substituted 3‐amino‐2‐en‐1‐ones are described. The utility of this catalysis is manifested by a wide scope of applicable N‐hydroxyl propargylamines and nucleophiles, thus enabling the design of one‐pot cascade or two‐step sequential reactions. Besides synthetic significances, such oxidative Mannich reactions are mechanistically interesting because structurally reorganized products were obtained. Our mechanistic studies reveal that the aerobic oxidations involve initial formation of nitrone intermediates, followed by the attack of nucleophiles. Herein, water and MeOH implement the conversion of nitrone intermediates to reaction products in two distinct pathways.     

Manganese‐Catalyzed Multicomponent Synthesis of Pyrimidines from Alcohols and Amidines

The development of catalytic reactions for synthesizing different compounds from alcohols to save fossil carbon feedstock and reduce CO₂ emissions is of high importance. Replacing rare noble metals with abundantly available 3d metals is equally important. We report a manganese‐complex‐catalyzed multicomponent synthesis of pyrimidines from amidines and up to three alcohols. Our reaction proceeds through condensation and dehydrogenation steps, permitting selective C−C and C−N bond formations. β‐Alkylation reactions are used to multiply alkylate secondary alcohols with two different primary alcohols to synthesize fully substituted pyrimidines in a one‐pot process. Our PN₅P‐Mn‐pincer complexes efficiently catalyze this multicomponent process. A comparison of our manganese catalysts with related cobalt catalysts indicates that manganese shows a reactivity similar to that of iridium but not cobalt. This analogy could be used to develop further (de)hydrogenation reactions with manganese complexes.