Catalytic C?C,C?N,and C?O Ullmann‐Type Coupling Reactions

Copper‐catalyzed Ullmann condensations are key reactions for the formation of carbon–heteroatom and carbon–carbon bonds in organic synthesis. These reactions can lead to structural moieties that are prevalent in building blocks of active molecules in the life sciences and in many material precursors. An increasing number of publications have appeared concerning Ullmann‐type intermolecular reactions for the coupling of aryl and vinyl halides with N, O, and C nucleophiles, and this Minireview highlights recent and major developments in this topic since 2004.     

Amide‐Directed Tandem C?C/C?N Bond Formation through C?H Activation

The transformation of C? H bonds into other chemical bonds is of great significance in synthetic chemistry. C? H bond‐activation processes provide a straightforward and atom‐economic strategy for the construction of complex structures; as such, they have attracted widespread interest over the past decade. As a prevalent directing group in the field of C? H activation, the amide group not only offers excellent regiodirecting ability, but is also a potential C? N bond precursor. As a consequence, a variety of nitrogen‐containing heterocycles have been obtained by using these reactions. This Focus Review addresses the recent research into the amide‐directed tandem C? C/C? N bond‐formation process through C? H activation. The large body of research in this field over the past three years has established it as one of the most‐important topics in organic chemistry.     

Oxindole Synthesis by Direct Coupling of C?H and C?H Centers

An sp ² /sp ³ get‐together : A novel and efficient method can be used to synthesize 3,3‐disubstitued oxindoles by the direct intramolecular oxidative coupling of an aryl C? H and a C? H center (see scheme; DMF=N,N‐dimethylformamide).

     

Bifunctional transition metal‐based molecular catalysts for asymmetric C?C and C?N bond formation

This paper describes the recent advances in the conceptually new bifunctional Ir and Ru catalysts for asymmetric catalytic reactions. These reactions include the enantioselective Michael addition of 1,3‐dicarbonyl compounds to cyclic enones and nitroalkenes, and the enantioselective direct amination of α‐cyanoacetates with diazoesters. The outcome of these reactions in terms of reactivity and selectivity was delicately influenced by the catalyst structures and the reaction conditions including the solvents used. Even with a 1 : 1 molar ratio of donors to acceptors, the reactions proceeded smoothly to give the corresponding chiral adducts with an excellent yield and enantiomeric excess (ee). Preliminary mechanistic studies showed that the key stage of the catalytic cycle is the interaction of the bifunctional catalyst with a pronucleophilic reagent that leads to stereoselective formation of C‐, O‐, or N‐bound complexes. The resulting protonated catalyst bearing metal‐bound nucleophiles readily reacts with electrophiles to provide C? C and C? N bond formation products in a highly stereoselective manner. © 2009 The Japan Chemical Journal Forum and Wiley Periodicals, Inc. Chem Rec 9: 106–123; 2009: Published online in Wiley InterScience ( www.interscience.wiley.com ) DOI 10.1002/tcr.20172     

Visible light-mediated photocatalyzed synthesis of oxazole via intermolecular C?N and C?O bond formation

An efficient visible light-mediated, eosin Y-catalyzed synthesis of oxazole has been developed from benzil with primary amines, that providing a straightforward, green, and environmentally benign access to a wide variety of substituted oxazole-2-amines under mild reaction conditions.     

Nitrene Insertion into C?C and C?H Bonds of Diamide Diimine Ligands Ligated to Chromium and Iron

The impact of redox non‐innocence (RNI) on chemical reactivity is a forefront theme in coordination chemistry. A diamide diimine ligand, [{‐CHN(1,2‐C₆H₄)NH(2,6‐iPr₂C₆H₃)}₂]ⁿ (n=0 to −4), (dadi)ⁿ, chelates Cr and Fe to give [(dadi)M] ([ 1 Cr(thf)] and [ 1 Fe]). Calculations show [ 1 Cr(thf)] (and [ 1 Cr]) to have a d⁴ Cr configuration antiferromagnetically coupled to (dadi)²⁻*, and [ 1 Fe] to be S=2. Treatment with RN₃ provides products where RN is formally inserted into the C C bond of the diimine or into a C H bond of the diimine. Calculations on the process support a mechanism in which a transient imide (imidyl) aziridinates the diimine, which subsequently ring opens.     

Nickel‐Catalyzed Enantioselective C?C Bond Formation through C?O Cleavage in Aryl Esters

We report the first enantioselective C C bond formation through C O bond cleavage using aryl ester counterparts. This method is characterized by its wide substrate scope and results in the formation of quaternary stereogenic centers with high yields and asymmetric induction.     

Rhodium(III)‐Catalyzed C?C and C?O Coupling of Quinoline N‐Oxides with Alkynes: Combination of C?H Activation with O‐Atom Transfer

[Cp*Rh^III]‐catalyzed C H activation of arenes assisted by an oxidizing N O or N N directing group has allowed the construction of a number of hetercycles. In contrast, a polar N O bond is well‐known to undergo O‐atom transfer (OAT) to alkynes. Despite the liability of N O bonds in both C H activation and OAT, these two important areas evolved separately. In this report, [Cp*Rh^III] catalysts integrate both areas in an efficient redox‐neutral coupling of quinoline N‐oxides with alkynes to afford α‐(8‐quinolyl)acetophenones. In this process the N O bond acts as both a directing group for C H activation and as an O‐atom donor.     

M4(CH2)4 Cubane‐Type Rare‐Earth Methylidene Complexes: Unique Reactivity toward Unsaturated C?O,C?N,and C?S Bonds

The reactivity of the cubane‐type rare‐earth methylidene complex [Cp′Lu(μ₃‐CH₂)]₄ ( 1 , Cp′=C₅Me₄SiMe₃) with various unsaturated electrophiles was investigated. The reaction of 1 with CO (1 atm) at room temperature gave the bis(ketene dianion)/dimethylidene complex [Cp′₄Lu₄(μ₃‐CH₂)₂(μ₃,η²‐O‐C?CH₂)₂] ( 2 ) in 86 % yield through the insertion of two molecules of CO into two of the four lutetium–methylidene units. In the reaction with the sterically demanding N,N‐diisopropylcarbodiimide at 60 °C, only one of the four methylidene units in 1 reacted with one molecule of the carbodiimide substrate to give the mono(ethylene diamido)/trimethylidene complex [Cp′₄Lu₄(μ₃‐CH₂)₃{iPrNC(=CH₂)NiPr}] ( 3 ) in 83 % yield. Similarly, the reaction of 1 with phenyl isothiocyanate gave the ethylene amido thiolate/trimethylidene complex [Cp′₄Lu₄(μ₃‐CH₂)₃{PhNC(S)=CH₂}] ( 4 ). In the case of phenyl isocyanate, two of the four methylidene units in 1 reacted with four molecules of the substrate at ambient temperature to give the malonodiimidate/dimethylidene complex [Cp′₄Lu₄(μ₃‐CH₂)₂{PhN=C(O)CH₂(O)C?NPh}₂] ( 5 ) in 87 % yield. In this reaction, each of the two lutetium–methylidene bonds per methylidene unit inserted one molecule of phenyl isocyanate. All the products have been fully characterized by NMR spectroscopy, X‐ray diffraction, and microelemental analyses.     

Palladium(II)‐Catalyzed C?H Activation/C?C Cross‐Coupling Reactions: Versatility and Practicality

Pick your Pd partners : A number of catalytic systems have been developed for palladium‐catalyzed C? H activation/C? C bond formation. Recent studies concerning the palladium(II)‐catalyzed coupling of C? H bonds with organometallic reagents through a Pd^II/Pd⁰ catalytic cycle are discussed (see scheme), and the versatility and practicality of this new mode of catalysis are presented. Unaddressed questions and the potential for development in the field are also addressed.

     

Alkyne Insertion into the M?P and M?H Bonds (M=Pd,Ni, Pt,and Rh): A Theoretical Mechanistic Study of the C?P and C?H Bond‐Formation Steps

In hydrogen‐metal‐phosphorus (H M P) transition metal complexes (proposed as intermediates of H P bond addition to alkynes in the catalytic hydrophosphorylation, hydrophosphinylation, and hydrophospination reactions), alkyne insertion into the metal‐hydrogen bond was found much more facile compared to alkyne insertion into the metal‐phosphorus bond. The conclusion was verified for different metals (Pd, Ni, Pt, and Rh), ligands, and phosphorus groups at various theory levels (B3LYP, B3PW91, BLYP, MP2, and ONIOM). The relative reactivity of the metal complexes in the reaction with alkynes was estimated and decreased in the order of Ni>Pd>Rh>Pt. A trend in relative reactivity was established for various types of phosphorus groups: PR₂>P(O)R₂>P(O)(OR)₂, which showed a decrease in rate upon increasing the number of the oxygen atoms attached to the phosphorus center.     

An Excursion from Normal to Inverted C?C Bonds Shows a Clear Demarcation between Covalent and Charge‐Shift C?C Bonds

What is the nature of the C? C bond? Valence bond and electron density computations of 16 C? C bonds show two families of bonds that flesh out as a phase diagram. One family, involving ethane, cyclopropane and so forth, is typified by covalent C? C bonding wherein covalent spin‐pairing accounts for most of the bond energy. The second family includes the inverted bridgehead bonds of small propellanes, where the bond is neither covalent nor ionic, but owes its existence to the resonance stabilization between the respective structures; hence a charge‐shift (CS) bond. The dual family also emerges from calculated and experimental electron density properties. Covalent C? C bonds are characterized by negative Laplacians of the density, whereas CS‐bonds display small or positive Laplacians. The positive Laplacian defines a region suffering from neighbouring repulsive interactions, which is precisely the case in the inverted bonding region. Such regions are rich in kinetic energy, and indeed the energy‐density analysis reveals that CS‐bonds are richer in kinetic energy than the covalent C? C bonds. The large covalent–ionic resonance energy is precisely the mechanism that lowers the kinetic energy in the bonding region and restores equilibrium bonding. Thus, different degrees of repulsive strain create two bonding families of the same chemical bond made from a single atomic constituent. It is further shown that the idea of repulsive strain is portable and can predict the properties of propellanes of various sizes and different wing substituents. Experimentally (M. Messerschmidt, S. Scheins, L. Bruberth, M. Patzel, G. Szeimies, C. Paulman, P. Luger, Angew. Chem. 2005 , 117, 3993–3997; Angew. Chem. Int. Ed. 2005 , 44, 3925–3928), the C? C bond families are beautifully represented in [1.1.1]propellane, where the inverted C? C is a CS‐bond, while the wings are made from covalent C? C bonds. What other manifestations can we expect from CS‐bonds? Answers from experiment have the potential of recharting the mental map of chemical bonding.     

Catalytic C?F Activation and Hydrodefluorination of Fluoroalkyl Groups

A powerful fluoride trap : The extremely Lewis acidic silyl cation [Et₃Si]⁺ is an active catalyst for the hydrodefluorination of fluoroalkyl groups at room temperature (see example). The carborane anion [CHB₁₁H₅Cl₆]^? plays an essential role in the catalytic cycle as a weakly coordinating anion that stabilizes cationic intermediates.