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.     

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.     

Simple Sulfinate Synthesis Enables C?H Trifluoromethylcyclopropanation

A simple method to convert readily available carboxylic acids into sulfinate salts by employing an interrupted Barton decarboxylation reaction is reported. A medicinally oriented panel of ten new sulfinate reagents was created using this method, including a key trifluoromethylcyclopropanation reagent, TFCS‐Na. The reactivity of six of these salts towards C H functionalization was field‐tested using several different classes of heterocycles.     

B?H,C?H,and B?C Bond Activation: The Role of Two Adjacent Agostic Interactions

Tuning the nature of the linker in a L∼BHR phosphinoborane compound led to the isolation of a ruthenium complex stabilized by two adjacent, δ‐C H and ε‐B_sp2 H, agostic interactions. Such a unique coordination mode stabilizes a 14‐electron “RuH₂P₂” fragment through connected σ‐bonds of different polarity, and affords selective B H, C H, and B C bond activation as illustrated by reactivity studies with H₂ and boranes.     

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.     

Manganese‐Catalyzed Dehydrogenative [4+2] Annulation of N?H Imines and Alkynes by C?H/N?H Activation

Described herein is a manganese‐catalyzed dehydrogenative [4+2] annulation of N H imines and alkynes, a reaction providing highly atom‐economical access to diverse isoquinolines. This transformation represents the first example of manganese‐catalyzed C H activation of imines; the stoichiometric variant of the cyclomanganation was reported in 1971. The redox neutral reaction produces H₂ as the major byproduct and eliminates the need for any oxidants, external ligands, or additives, thus standing out from known isoquinoline synthesis by transition‐metal‐catalyzed C H activation. Mechanistic studies revealed the five‐membered manganacycle and manganese hydride species as key reaction intermediates in the catalytic cycle.     

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.     

Catalytic Methylation of C?H Bonds Using CO2 and H2

Formation of C C bonds from CO₂ is a much sought after reaction in organic synthesis. To date, other than C H carboxylations using stoichiometric amounts of metals, base, or organometallic reagents, little is known about C C bond formation. In fact, to the best of our knowledge no catalytic methylation of C H bonds using CO₂ and H₂ has been reported. Described herein is the combination of CO₂ and H₂ for efficient methylation of carbon nucleophiles such as indoles, pyrroles, and electron‐rich arenes. Comparison experiments which employ paraformaldehyde show similar reactivity for the CO₂/H₂ system.     

The Redox‐Neutral Approach to C?H Functionalization

The direct functionalization of C? H bonds is an attractive strategy in organic synthesis. Although several advances have been made in this area, the selective activation of inert sp³ C? H bonds remains a daunting challenge. Recently, a new type of sp³ C? H activation mode through internal hydride transfer has demonstrated the potential to activate remote sp³ C? H linkages in an atom‐economic manner. This Minireview attempts to classify recent advances in this area including the transition to non‐activated sp³ C? H bonds and asymmetric hydride transfers.     

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.     

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.     

C?H Functionalization/Asymmetric Michael Addition Cascade Enabled by Relay Catalysis: Metal Carbenoid Used for C?C Bond Formation

A combination of either ruthenium(II) or rhodium(II) complexes and quinine‐derived squaramide enables 3‐diazooxindoles, indoles, and nitroalkenes to undergo highly efficient asymmetric three‐component reactions, thus affording optically active 3,3′‐bis(indole)s through a consecutive C C bond‐forming sequence, which turned out to be applicable to the facile total synthesis of (−)‐folicanthine.