Aerobic and Electrochemical Oxidative Cross‐Dehydrogenative‐Coupling (CDC) Reaction in an Imidazolium‐Based Ionic Liquid

The ionic liquid 1‐butyl‐3‐methylimidazolium tetrafluoroborate [BMIm][BF₄] has demonstrated high efficiency when applied as a solvent in the oxidative nitro‐Mannich carbon? carbon bond formation. The copper‐catalyzed cross‐dehydrogenative coupling (CDC) between N‐phenyltetrahydroisoquinoline and nitromethane in [BMIm][BF₄] occurred with high yield under the described reaction conditions. Both the ionic liquid and copper catalyst were recycled nine times with almost no lost of activity. The electrochemical behavior of the tertiary amine substrate and β‐nitroamine product was investigated employing [BMIm][BF₄] as electrolyte solvent. The potentiostatic electrolysis in ionic liquid afforded the desired product with a high yield. This result and the cyclic voltammetric investigation provide a better understanding of the reaction mechanism, which involves radical and iminium cation intermediates.     

Mechanistic Insights into the One‐Pot Synthesis of Propargylamines from Terminal Alkynes and Amines in Chlorinated Solvents Catalyzed by Gold Compounds and Nanoparticles

Propargylamines can be obtained from secondary amines and terminal alkynes in chlorinated solvents by a three‐ and two‐component synthesis catalyzed by gold compounds and nanoparticles (Au‐NP) under mild conditions. The use of dichloromethane allows for the activation of two C? Cl bonds and a clean transfer of the methylene fragment to the final product. The scope of the reaction as well as the influence of different gold(III) cycloaurated complexes and salts has been investigated. The involvement of gold nanoparticles generated in situ in the process is discussed and a plausible reaction mechanism is proposed on the basis of the data obtained.     

Zirconium-mediated coupling reactions of amines and enol or allyl ethers: synthesis of allyl- and homoallylamines

An easy and efficient zirconium-mediated synthesis of allylamines from simple amines and enol ethers is described. This strategy also allows the synthesis of amino alcohol derivatives containing a Z double bond in their structure when 2,3-dihydrofuran is used. Simple conventional modification of these amino alcohols leads to 2-substituted piperidine derivatives. By applying this approach, a formal total synthesis of the alkaloid coniine is easily achieved from a protected butylamine. Finally, the zirconium-mediated reaction of amines and allyl phenyl ether furnishes homoallylamines or amino ethers depending on the structure of the starting amine.     

“Design” of Boron‐Based Compounds as Pro‐Nucleophiles and Co‐Catalysts for Indium(I)‐Catalyzed Allyl Transfer to Various Csp3‐Type Electrophiles

We have recently uncovered a general indium(I)‐catalyzed method for allylations and propargylation of acetals and ketals with a water‐ and air‐stable allyl boronate. By using a more reactive allyl borane, we have successfully extended this methodology to the more challenging C C coupling with ethers. Herein, we report an improved methodology for the indium(I)‐catalyzed allylation of acetals and ethers, through combination of the allyl boronate with a commercially available “hard” Lewis acid, B‐methoxy‐9‐BBN (BBN=borabicyclo[3.3.1]nonane), as an effective co‐catalyst. Significantly, our work highlights for the first time the correlation between the Lewis acidity of “electrophilic” boron‐based compounds and their “nucleophilic” reactivity in Csp³–Csp³ couplings, catalyzed by a “soft” low‐oxidation main group metal. In addition, we also report several applications of these methodologies to the selective synthesis of various carbohydrate derivatives.     

Electrophilic Reactivities of 1,2‐Diaza‐1,3‐dienes

The kinetics of the reactions of 1,2‐diaza‐1,3‐dienes 1 with acceptor‐substituted carbanions 2 have been studied at 20 °C. The reactions follow a second‐order rate law, and can be described by the linear free energy relationship log k(20 °C)=s(N+E) [Eq. (1)]. With Equation (1) and the known nucleophile‐specific parameters N and s for the carbanions, the electrophilicity parameters E of the 1,2‐diaza‐1,3‐dienes 1 were determined. With E parameters in the range of ?13.3 to ?15.4, the electrophilic reactivities of 1 a–d are comparable to those of benzylidenemalononitriles, 2‐benzylideneindan‐1,3‐diones, and benzylidenebarbituric acids. The experimental second‐order rate constants for the reactions of 1 a – d with amines 3 and triarylphosphines 4 agreed with those calculated from E, N, and s, indicating the applicability of the linear free energy relationship [Eq. (1)] for predicting potential nucleophilic reaction partners of 1,2‐diaza‐1,3‐dienes 1 . Enamines 5 react up to 10² to 10³ times faster with compounds 1 than predicted by Equation (1), indicating a change of mechanism, which becomes obvious in the reactions of 1 with enol ethers.     

Transmetallation Versus β‐Hydride Elimination: The Role of 1,4‐Benzoquinone in Chelation‐Controlled Arylation Reactions with Arylboronic Acids

The formation of an atypical, saturated, diarylated, Heck/Suzuki, domino product produced under oxidative Heck reaction conditions, employing arylboronic acids and a chelating vinyl ether, has been investigated by DFT calculations. The calculations highlight the crucial role of 1,4‐benzoquinone (BQ) in the reaction. In addition to its role as an oxidant of palladium, which is necessary to complete the catalytic cycle, this electron‐deficient alkene opens up a low‐energy reaction pathway from the post‐insertion σ‐alkyl complex. The association of BQ lowers the free‐energy barrier for transmetallation of the σ‐alkyl complex to create a pathway that is energetically lower than the oxidative Heck reaction pathway. Furthermore, the calculations showed that the reaction is made viable by BQ‐mediated reductive elimination and leads to the saturated diarylated product.     

Deprotonation of C‐Alkyl Groups of Cationic Triruthenium Clusters Containing Cyclometalated C‐Alkylpyrazinium Ligands: Experimental and Computational Studies

The C‐alkyl groups of cationic triruthenium cluster complexes of the type [Ru₃(μ‐H)(μ‐κ²N¹,C² ‐L)(CO)₁₀]⁺ (HL represents a generic C‐alkyl‐N‐methylpyrazium species) have been deprotonated to give kinetic products that contain unprecedented C‐alkylidene derivatives and maintain the original edge‐bridged decacarbonyl structure. When the starting complexes contain various C‐alkyl groups, the selectivity of these deprotonation reactions is related to the atomic charges of the alkyl H atoms, as suggested by DFT/natural‐bond orbital (NBO) calculations. Three additional electronic properties of the C‐alkyl C? H bonds have also been found to correlate with the experimental regioselectivity because, in all cases, the deprotonated C? H bond has the smallest electron density at the bond critical point, the greatest Laplacian of the electron density at the bond critical point, and the greatest total energy density ratio at the bond critical point (computed by using the quantum theory of atoms in molecules, QTAIM). The kinetic decacarbonyl products evolve, under appropriate reaction conditions that depend upon the position of the C‐alkylidene group in the heterocyclic ring, toward face‐capped nonacarbonyl derivatives (thermodynamic products). The position of the C‐alkylidene group in the heterocyclic ring determines the distribution of single and double bonds within the ligand ring, which strongly affects the stability of the neutral decacarbonyl complexes and the way these ligands coordinate to the metal atoms in the nonacarbonyl products. The mechanisms of these decacarbonylation processes have been investigated by DFT methods, which have rationalized the structures observed for the final products and have shed light on the different kinetic and thermodynamic stabilities of the reaction intermediates, thus explaining the reaction conditions experimentally required by each transformation.     

Post‐Modification of meso–meso‐Linked Porphyrin Arrays by Iridium and Rhodium Catalyses for Tuning of Energy Gap

Skillfully attached! meso–meso‐Linked diporphyrins can be efficiently and selectively functionalized with multiple unsaturated carboxylic acid groups through iridium and rhodium catalyses. This post‐modification strategy allows fine‐tuning of energy levels of each porphyrin unit.

     

Bifunctional Heterogeneous Catalysis of Silica–Alumina‐Supported Tertiary Amines with Controlled Acid–Base Interactions for Efficient 1,4‐Addition Reactions

We report the first tunable bifunctional surface of silica–alumina‐supported tertiary amines (SA–NEt₂) active for catalytic 1,4‐addition reactions of nitroalkanes and thiols to electron‐deficient alkenes. The 1,4‐addition reaction of nitroalkanes to electron‐deficient alkenes is one of the most useful carbon–carbon bond‐forming reactions and applicable toward a wide range of organic syntheses. The reaction between nitroethane and methyl vinyl ketone scarcely proceeded with either SA or homogeneous amines, and a mixture of SA and amines showed very low catalytic activity. In addition, undesirable side reactions occurred in the case of a strong base like sodium ethoxide employed as a catalytic reagent. Only the present SA‐supported amine (SA–NEt₂) catalyst enabled selective formation of a double‐alkylated product without promotions of side reactions such as an intramolecular cyclization reaction. The heterogeneous SA–NEt₂ catalyst was easily recovered from the reaction mixture by simple filtration and reusable with retention of its catalytic activity and selectivity. Furthermore, the SA–NEt₂ catalyst system was applicable to the addition reaction of other nitroalkanes and thiols to various electron‐deficient alkenes. The solid‐state magic‐angle spinning (MAS) NMR spectroscopic analyses, including variable‐contact‐time ¹³C cross‐polarization (CP)/MAS NMR spectroscopy, revealed that acid–base interactions between surface acid sites and immobilized amines can be controlled by pretreatment of SA at different temperatures. The catalytic activities for these addition reactions were strongly affected by the surface acid–base interactions.     

Palladium‐Catalyzed Carbon–Carbon Bond Formation and Cleavage of Organo(hydro)fullerenes

Palladium can tailor fullerenes : Palladium catalysts enable a number of C? H bond transformations of organo(hydro)fullerene. In addition to anticipated coupling reactions (C? H bond allylation and arylation), an unexpected new C? H bond dimerization reaction and C? C bond‐cleavage reaction were also uncovered.

     

A Robust Palladium(II)–Porphyrin Complex as Catalyst for Visible Light Induced Oxidative C?H Functionalization

A series of palladium(II)–porphyrin complexes that display dual emissions with lifetimes up to 437 μs have been synthesized. Among the four complexes, PdF₂₀TPP is an efficient and robust catalyst for photoinduced oxidative C? H functionalization by using oxygen as terminal oxidant. α‐Functionalized tertiary amines were obtained in good to excellent yields by light irradiation (λ>400 nm) of a mixture of PdF₂₀TPP , tertiary amine, and nucleophile (cyanide, nitromethane, dimethyl malonate, diethyl phosphite, and acetone) under aerobic conditions. Four examples of intramolecular cyclized amine compounds could be similarly prepared. Comparison of the UV‐visible absorption spectra before and after the photochemical reaction revealed that PdF₂₀TPP was highly robust (>95 % recovery). The practical application of PdF₂₀TPP has been revealed by the photochemical reactions performed by using a low catalyst loading (0.01 mol %) and on a 10 mmol scale. The PdF₂₀TPP catalyst could sensitize photoinduced oxidation of sulfides to sulfoxides in excellent yields. Mechanistic studies revealed that the photocatalysis proceeded by singlet‐oxygen oxidation.     

Rhodium‐Catalyzed Oxidative Coupling between Salicylaldehydes and Internal Alkynes with C?H Bond Cleavage To Produce 2,3‐Disubstituted Chromones

A direct oxidative coupling of salicylaldehydes with internal alkynes proceeds efficiently with cleavage of the aldehyde C? H bond to produce the corresponding chromone derivatives. A rhodium catalyst in combination with a cyclopentadiene ligand and a copper oxidant promote this straightforward annulation reaction. Solid‐state luminescence was observed for certain chromone products.     

Cover Picture: Palladium‐Catalyzed Carbon–Carbon Bond Formation and Cleavage of Organo(hydro)fullerenes (Chem. Eur. J. 19/2009)

An unexpected C? H bond dimerization reaction and C? C bond‐cleavage reaction in organo(hydro)fullerenes have been discovered. In their Communication on page 4760 ff. , K. Itami and M. Nambo describe the use of Pd catalysts for a number of interesting reactions of such fullerenes.

     

Aldehyde‐Assisted Hydrogen Transfer during the Formation of Hydride–Iridafurans from Alkynes and Aldehydes

The bis(ethylene) Ir^I complex [TpIr(C₂H₄)₂] ( 1 ; Tp=hydrotris(3,5‐dimethylpyrazolyl)borate) reacts with two equivalents of aromatic or aliphatic aldehydes in the presence of one equivalent of dimethyl acetylenedicarboxylate (DMAD) with ultimate formation of hydride iridafurans of the formula [TpIr(H){C(R¹)?C(R²)C(R³)O }] (R¹=R²=CO₂Me; R³=alkyl, aryl; 3 ). Several intermediates have been observed in the course of the reaction. It is proposed that the key step of metallacycle formation is a C? C coupling process in the undetected Ir^I species [TpIr{η¹‐O‐R³C(?O)H}(DMAD)] ( A ) to give the trigonal‐bipyramidal 16 e^? Ir^III intermediates [TpIr{C(CO₂Me)?C(CO₂Me)C(R³)(H)O }] ( C ), which have been trapped by NCMe to afford the adducts 11 (R³=Ar). If a second aldehyde acts as the trapping reagent for these species, this ligand acts as a shuttle in transfering a hydrogen atom from the γ‐ to the α‐carbon atom of the iridacycle through the formation of an alkoxide group. Methyl propiolate (MP) can be used instead of DMAD to regioselectively afford the related iridafurans. These reactions have also been studied by DFT calculations.     

Cobalt‐Mediated Linear 2:1 Co‐oligomerization of Alkynes with Enol Ethers to Give 1‐Alkoxy‐1,3,5‐Trienes: A Missing Mode of Reactivity

A variety of 1,6‐heptadiynes and certain borylalkynes co‐oligomerize with enol ethers in the presence of [CpCo(C₂H₄)₂] (Cp=cyclopentadienyl) to furnish the hitherto elusive acyclic 2:1 products, 1,3,5‐trien‐1‐ol ethers, in preference to or in competition with the alternative pathway that leads to the standard [2+2+2] cycloadducts, 5‐alkoxy‐1,3‐cyclohexadienes. Minor variations, such as lengthening the diyne tether, cause reversion to the standard mechanism. The trienes, including synthetically potent borylated derivatives, are generated with excellent levels of chemo‐, regio‐, and diastereoselectivity, and are obtained directly by decomplexation of the crude mixtures during chromatography. The cyclohexadienes are isolated as the corresponding dehydroalkoxylated arenes. In one example, even ethene functions as a linear cotrimerization partner. The alkoxytrienes are thermally labile with respect to 6π‐electrocyclization–elimination to give the same arenes that are the products of cycloaddition. The latter, regardless of the mechanism of their formation, can be viewed as the result of a formal [2+2+2] cyclization of the starting alkynes with acetylene. One‐pot conditions for the exclusive formation of arenes are developed. DFT computations indicate that cyclohexadiene and triene formation share a common intermediate, a cobaltacycloheptadiene, from which reductive elimination and β‐hydride elimination compete.     

Tertiary Carbinamine Synthesis by Rhodium‐Catalyzed [3+2] Annulation of N‐Unsubstituted Aromatic Ketimines and Alkynes

A convenient and waste‐free synthesis of indene‐based tertiary carbinamines by rhodium‐catalyzed imine/alkyne [3+2] annulation is described. Under the optimized conditions of 0.5–2.5 mol % [{(cod)Rh(OH)}₂] (cod=1,5‐cyclooctadiene) catalyst, 1,3‐bis(diphenylphosphanyl)propane (DPPP) ligand, in toluene at 120 °C, N‐unsubstituted aromatic ketimines and internal alkynes were coupled in a 1:1 ratio to form tertiary 1H‐inden‐1‐amines in good yields and with high selectivities over isoquinoline products. A plausible catalytic cycle involves sequential imine‐directed aromatic C? H bond activation, alkyne insertion, and a rare example of intramolecular ketimine insertion into a Rh^I–alkenyl linkage.     

Rapid Access to 2,2′‐Bithiazole‐Based Copolymers via Sequential Palladium‐Catalyzed C–H/C–X and C–H/C–H Coupling Reactions

A rapid access to 2,2′‐bithiazole‐based copolymers has been developed on the basis of the sequential palladium‐catalyzed C H/C X and C H/C H coupling reactions. To assemble a “copolymer” through homopolymerization, a type of symmetric A‐B‐A‐type building block is designed as the monomer and prepared via the regioselective C5 H arylation of thiazole. A PdCl₂/CuCl‐cocatalyzed oxidative C H/C H homopolymerization has been established to afford the 2,2′‐bithiazole‐based copolymers with high M_n (up to 69400). The current protocol features atom‐ and step‐economy and exhibits a potential in the highly efficient construction of conjugated copolymers.

     

Rhodium‐Catalyzed Oxidative C–H Activation/Cyclization for the Synthesis of Phosphaisocoumarins and Phosphorous 2‐Pyrones

Rhodium‐catalyzed cyclization of phosphinic acids and phosphonic monoesters with alkynes has been developed. The oxidative annulation proceeds with complete conversion of phosphinic acid derivatives and allowed the atom‐economic preparation of useful phosphaisocoumarins with high yield and selectivity. The reaction is tolerant of extensive substitution on the phosphinic acid, phosphonic monoester and alkyne, including halides, ketone, and hydroxyl groups as substituents. Furthermore, we found that alkenylphosphonic monoesters proceed to give a wide range of phosphorus 2‐pyrones through oxidative annulation with alkynes. Mechanistic studies revealed that C? H bond metalation was the rate‐limiting step.     

Investigation and Comparison of the Mechanistic Steps in the [(Cp*MCl2)2] (Cp*=C5Me5; M=Rh,Ir)‐Catalyzed Oxidative Annulation of Isoquinolones with Alkynes

The mechanism of the [(Cp*MCl₂)₂] (M=Rh, Ir)‐catalyzed oxidative annulation reaction of isoquinolones with alkynes was investigated in detail. In the first acetate‐assisted C? H‐activation process (cyclometalated step) and the subsequent mono‐alkyne insertion into the M? C bonds of the cyclometalated compounds, both Rh and Ir complexes participated well. However, the desired final products, dibenzo[a,g]quinolizin‐8‐one derivatives, were only formed in high yield when the Rh species participated in the final oxidative coupling of the C? N bond. Moreover, a Rh^I sandwich intermediate was isolated during this transformation. The iridium complexes were found to be inactive in the oxidative coupling processes. All of the relevant intermediates were fully characterized and determined by single‐crystal X‐ray diffraction analysis. Based on this mechanistic study, a Rh^III→Rh^I→Rh^III catalytic cycle was proposed for this reaction.     

RhI‐Catalyzed Regio‐ and Stereospecific Carbonylation of 1‐(1‐Alkynyl)cyclopropyl Ketones: A Modular Entry to Highly Substituted 5,6‐Dihydrocyclopenta[c]furan‐4‐ones

Efficient route : A novel Rh^I‐catalyzed regio‐ and stereospecific carbonylation reaction of (1‐alkynyl)cyclopropyl ketones by selective activation of a carbon? carbon σ bond of the cyclopropane ring was demonstrated (see scheme). This method provides a general, efficient, stereoselective route to synthesise 1,3,5‐trisubstituted and 1,3,5,6‐tetrasubstituted 5,6‐dihydrocyclopenta[c]furan‐4‐one with convertible functional groups.