Copper‐Catalyzed Synthesis of α‐Thioaryl Carbonyl Compounds Through S?S and C?C Bond Cleavage

A method to access α‐thioaryl ketones and α‐thioaryl esters employing copper acetate (hydrate) as catalyst and readily accessible diaryl disulfides and β‐diketones (or β‐keto esters) has been developed. Both alkyl‐ and aryl‐substituted carbonyl compounds can be prepared.

     

Iron‐Catalyzed C?C Bond Cleavage and C?N Bond Formation

A novel approach for C N bond formation was developed by iron‐catalyzed C C bond cleavage. Anilines and sulfonamides reacted smoothly with 2‐substituted 1,3‐diphenylpropane‐1,3‐diones to afford N‐alkylation products, in which the 1,3‐dicarbonyl group acts as a leaving group in the presence of an iron catalyst. The reversible C C bond cleavage plays a driving force to give the thermodynamically stable products. The method is complementary to the previous methods for C N bond formation.     

Zinc‐Catalyzed Organic Synthesis: C?C,C?N,C?O Bond Formation Reactions

Zinc is the 24^th most abundant element in the Earth’s crust. Since the discovery of pure zinc metal in the 18^th century, the main application of zinc metal is as materials. Because zinc salts are abundant, cheap, non‐toxic, and exhibit environmentally benign properties, organic chemists have been interested in using zinc salts as catalysts in organic synthesis during the last three decades. Within this review, we have summarized the progress on applications of zinc salts in organic reactions. Our the target is to emphasize the special properties of zinc catalysts, and further promote the interest of organic chemists.     

α,β‐Unsaturated Aldehydes as Substrates for Asymmetric C?C Bond Forming Reactions with Thiamin Diphosphate (ThDP)‐Dependent Enzymes

The enzymes benzaldehyde lyase (BAL) from Pseudomonas fluorescens, benzoylformate decarboxylase (BFD) from Pseudomonas putida and pyruvate decarboxylase (PDC) from Saccharomyces cerevisiae provide different C C bond forming possibilities of α,β‐unsaturated aldehydes with aliphatic and aromatic aldehydes. Structure elucidation and determination of the absolute configuration of the products, which were obtained with high regio‐ and stereoselectivity were carried out. Selective 1,2‐reactivity with yields of 75% and >98% ee, for one single isomer ( A ) were obtained, by choosing the suitable enzyme in combination with the appropriate substrates. By varying enzymes or substrates the regioisomeric hydroxy ketones C , with up to >99% ee, can be obtained. The application of these new chiral building blocks in the synthesis of natural products or biological active substances is considerably facilitated by applying the different ThDP‐dependent enzymes as catalysts. Abbreviations: BAL, benzaldehyde lyase; BFD, benzoylformate decarboxylase; PDC, pyruvate decarboxylase; His, hexahistidine; 2‐HPP, 2‐hydroxy‐1‐phenylpropan‐1‐one; PAC, phenylacetylcarbinol; NTA, nitrilotriacetic acid; ThDP, thiamin diphosphate; wt, wild‐type.     

Recent Developments in Enzymatic Asymmetric C?C Bond Formation

Some of the recent developments in enzymatic asymmetric C C bond formation are described in this review. The close relationship of biocatalysis and biosynthesis is highlighted with a special emphasis on diversity and biogenesis. One focus of this review is the creation of tetrasubstituted carbon stereocenters. Members of the supposedly well‐known aldolase and hydroxynitrile lyase enzyme families possess the ability to catalyze the formation of tertiary alcohols. In the case of aldolases, this can occur through intramolecular cyclization or intermolecular asymmetric C C bond formation. Thiamine diphosphate‐dependent YerE has been identified as a potent catalyst for the acyloin condensation with ketones as acceptor substrates. C₁ transformations such as methylation or carboxylation are catalyzed in an asymmetric manner by enzymes from different classes, for example S‐adenosylmethionine‐dependent (radical) enzymes or NADPH‐dependent oxidoreductases. Insights from biosynthetic and mechanistic studies of enzymatic reactions proceeding via radical intermediates give valuable hints towards possible applications in biocatalysis. Still, the oxygen sensitivity of many of these biocatalysts poses a considerable challenge for practical applications.     

Iron‐Catalyzed Esterification of Benzyl C?H Bonds to Form α‐Keto Benzyl Esters

An atom‐economic and efficient non‐precious metal‐catalyzed esterification of benzyl C H bonds has been developed. A variety of α‐keto benzyl esters have been accessed in good yields through the reactions between benzyl derivatives and benzoylformic acids using iron trifluoride as a catalyst in the presence of di‐tert‐butyl peroxide under an inert atmosphere. This strategy provides a straightforward access to linearly expanded α‐keto benzyl esters. A plausible reaction mechanism is proposed.

     

Mechanistic Switch via Subtle Ligand Modulation: Palladium‐Catalyzed Synthesis of α,β‐Substituted Styrenes via C?H Bond Functionalization

A new catalyst system able to efficiently perform the synthesis of styrenes via C H bond functionalization and a subtle ligand modification are described. The high level of activity achieved allows for the synthesis of highly functionalized α,β‐substituted styrenes, even the elusive E‐configured trisubstituted olefins, in a regio‐ and stereoselective manner. Mechanistic experiments allowed for the identification of the corresponding synthetic intermediates.     

Nickel‐Catalyzed α‐Benzylation of Arylacetonitriles via C?O Activation

Efficient Ni‐catalyzed direct cross‐couplings of benzylic alcohol derivatives with arylacetonitriles via C O activation are described. Various α‐benzylated arylacetonitriles including those with functional groups can be prepared under mild reaction conditions.

     

Carbon Nitride‐Catalyzed Photoredox C?C Bond Formation with N‐Aryltetrahydroisoquinolines

In this communication we describe the oxidative C C bond formation of tertiary amines with various nucleophiles under very mild and environmental friendly conditions by using mesoporous graphitic carbon nitride (mpg‐C₃N₄) semiconductor as a heterogeneous, metal‐free photosensitizer in combination with visible light and oxygen as the terminal oxidation agent. This system can be further combined with proline‐organocatalysis to achieve oxidative tandem photocatalysis, demonstrating a rich cascade of chemical possibilities of the current photosynthesis system.     

Asymmetric meso‐Epoxide Ring‐Opening with Trimethylsilyl Cyanide Promoted by Chiral Binuclear Complexes of Titanium. Dichotomy of C?C versus C?N Bond Formation

In the presence of chiral catalysts derived from the same chiral hexadentate ligand and aluminium, zinc or titanium ions, the reaction between cyclohexene oxide and trimethylsilyl cyanide can be controlled to give predominantly either the nitrile (up to 99% ee) or the isonitrile product (up to 94% ee). The metal ion, ligand stereochemistry and base concentration all play a role in determining the product ratio.     

Copper Catalysts for Selective C?C Bond Cleavage of β‐O‐4 Lignin Model Compounds

The reactivity of homogeneous copper catalysts towards the selective C C bond cleavage of both phenolic and non‐phenolic arylglycerol β‐aryl ether lignin model compounds has been explored. Several copper precursors, nitrogen ligands, and solvents were evaluated in order to optimize the catalyst system. Using the optimized catalyst system, copper(I) trifluoromethanesulfonate [Cu(OTf)]/L/TEMPO (L=2,6‐lutidine, TEMPO=2,2,6,6‐tetramethyl‐piperidin‐1‐yl‐oxyl), aerobic oxidation of the non‐phenolic β‐O‐4 lignin model compound proceeded with good selectivity for C_α C_β bond cleavage, affording 3,5‐dimethoxybenzaldehyde as the major product. Aerobic oxidation of the corresponding phenolic β‐O‐4 lignin model proceeded with different selectivity, affording 2,6‐dimethoxybenzoquinone and α,β‐unsaturated aldehyde products resulting from cleavage of the C_α C_aryl bond. At low catalyst concentrations, however, a change in selectivity was observed as oxidation of the benzylic secondary alcohol predominated with both substrates.

     

Diruthenium(I,I) Catalysts for the Formation of β‐ and γ‐Lactams via Carbenoid C?H Insertion of α‐Diazoacetamides

Intramolecular carbenoid C H insertion of five α‐diazoacetamides [N₂CH CONR₂, NR₂=NEt₂ ( 3a ), NBu₂ ( 3b ), N(i‐Pr)₂ ( 3c ), N(CH₂Ph)₂ ( 3d ), N(i‐Pr)(CH₂Ph) ( 3e )], was investigated using as catalysts dinuclear Ru(I,I) complexes of the type [Ru₂(μ‐L¹)₂(CO)₄L²₂], where L¹ is a bidentate bridging acetate, calix[4]arenedicarboxylate, saccharinate, pyridin‐2‐olate, or triazenide ligand, as well as [RuCl₂(p‐cymene)]₂. The Ru(I,I) complexes were found to be suitable catalysts for the carbenoid cyclization reactions, except in the case of 3a . With diazoamides 3b–e , [Ru₂(μ‐sac)₂(CO)₅]₂ (sac=saccharinate) and [Ru₂(μ‐6‐chloropyridin‐2‐olate)₂(CH₃CN)₂(CO)₄] are as effective as Rh₂(OAc)₄ under the same conditions, although some differences in the regioselectivity and chemoselectivity of the cyclization are observed. The carbenoid cyclization reactions yield γ‐lactams from diazoamides 3a and 3b , both a β‐ and a γ‐lactam from 3c , and a β‐lactam as well as a 3‐azabicyclo[5.3.0]deca‐5,7,9‐trien‐2‐one from 3d . With 3e , formation of γ‐lactam 21 and of bicyclic lactam 23 prevails.     

Iron(II)‐Promoted Synthesis of 2‐Aminothiazoles via C?N Bond Formation from Vinyl Azides and Potassium Thiocyanate

A simple protocol to prepare the privileged 2‐aminothiazoles promoted by ferrous sulfate heptahydrate via C N bond formation from vinyl azides and commercially available potassium thiocyanate has been developed. A wide range of vinyl azides are tolerated to afford the expected polysubstituted 2‐aminothiazoles in reasonably good yields. The use of the non‐toxic substrates and catalyst renders the reaction more environmentally friendly than traditional approaches.

     

C?H Functionalization of Enamides: Synthesis of β‐Amidovinyl Sulfones via Visible‐Light Photoredox Catalysis

A mild, practical and environmentally friendly strategy to prepare β‐amidovinyl sulfones has been developed based on the sulfonation of enamides or enecarbamates via visible‐light photoredox catalysis. Direct C H functionalizations of enamides or enecarbamates under the optimized conditions proceeded with a wide scope of substrates and remarkable selectivity to give functionalized vinyl sulfones with good to excellent yields.     

Chemo‐Controlled Cross‐Coupling of Di(hetero)aryl Disulfides with Grignard Reagents: C?C vs. C?S Bond Formation

A general protocol for the chemoselectivity‐controlled C C and C S coupling reactions of di(hetero)aryl disulfides with Grignard reagents catalyzed by ferrocene and palladium acetate has been developed. Ferrocene favored the formation of C S coupled products at low temperature, whereas C C bond couplings were favored when palladium acetate was used. All the reactions proceeded with excellent chemoselectivity and in good yields under mild conditions, and a library of molecules with pyridine and pyrimidine scaffolds was produced.

     

Nickel‐Catalyzed C?S Bond Formation: Synthesis of Aryl Sulfides from Arylsulfonyl Hydrazides and Boronic Acids

A practical nickel‐catalysed approach has been developed for the C S bond formation through the cross‐coupling of arylsulfonyl hydrazides and aryl boronic acids. The report employs arylsulfonyl hydrazide as an aryl thiol equivalent and offers a mild and eco‐safe synthesis of unsymmetrical thioethers in good to excellent yields in air. The scope and versatility of the method has been successfully demonstrated with 22 examples.

     

Building Functionality through Sequential C?B and C?F Bond Formation

α′‐Fluoro β‐boryl ketones can be efficiently synthesised from a sequential organocatalytic β‐boration pathway and consecutive electrophilic fluorination reaction in an acidic medium. Alternatively, the regioisomers of α‐fluoro β‐boryl ketones can be diastereoselectively obtained from Cu(I)‐mediated β‐boration followed by in situ fluorination of the boron enolate. Enantioenriched mixtures of the major anti‐diastereomer of vicinal C B and C F bonds are found in the presence of the chiral ligand QuinoxP*.     

C?C Bond Formation via C?H Activation and C?N Bond Formation via Oxidative Amination Catalyzed by Palladium‐ Polyoxometalate Nanomaterials Using Dioxygen as the Terminal Oxidant

An efficient heterogeneous palladium‐polyoxometalate catalyst with the formula Pd‐H₆PV₃Mo₉O₄₀/C has been successfully developed for carbon‐carbon (C C) bond formation via carbon‐hydrogen (C H) activation and carbon‐nitrogen (C N) bond formation via oxidative amination using oxygen as the terminal oxidant. The coupling processes are simple, and use relatively mild conditions to form the desired products. In addition, less waste is generated as no additional reagents such as organic/inorganic oxidants are required, and water is the only by‐product generated.     

Palladium‐Catalyzed Oxidative Intramolecular C?C Bond Formation via Double sp2 C?H Activation between the 2‐Position of Imidazoles and a Benzene Ring

Oxidative intramolecular C C bond formation via double sp² C H activation between the 2‐position of imidazoles and a benzene ring catalyzed by palladium(II) has been developed, which provides an atom‐economical, concise and efficient methodology to synthesize imidazole‐ or benzimidazole‐fused isoquinoline polyheteroaromatic compounds.     

Copper(II) Acetate/Oxygen‐Mediated Nucleophilic Addition and Intramolecular C?H Activation/C?N or C?C Bond Formation: One‐Pot Synthesis of Benzimidazoles or Quinazolines

Diarylcarbodiimides or benzylphenylcarbodiimides are converted to 1,2‐disubstituted benzimidazoles or 1,2‐disustituted quinazolines via addition/intramolecular C H bond activation/C‐N or C C bond forming reaction using copper(II) acetate/oxygen [Cu(OAc)₂/O₂] as the oxidant at 100 °C in one‐pot cascade procedure.