Transition-Metal-Catalyzed C–H Bond Activation for the Formation of C–C Bonds in Complex Molecules

Abstract

Site-predictable and chemoselective C–H bond functionalization reactions offer synthetically powerful strategies for the step-economic diversification of both feedstock and fine chemicals. Many transition-metal-catalyzed methods have emerged for the selective activation and functionalization of C–H bonds. However, challenges of regio- and chemoselectivity have emerged with application to highly complex molecules bearing significant functional group density and diversity. As molecular complexity increases within molecular structures the risks of catalyst intolerance and limited applicability grow with the number of functional groups and potentially Lewis basic heteroatoms. Given the abundance of C–H bonds within highly complex and already diversified molecules such as pharmaceuticals, natural products, and materials, design and selection of reaction conditions and tolerant catalysts has proved critical for successful direct functionalization. As such, innovations within transition-metal-catalyzed C–H bond functionalization for the direct formation of carbon–carbon bonds have been discovered and developed to overcome these challenges and limitations. This review highlights progress made for the direct metal-catalyzed C–C bond forming reactions including alkylation, methylation, arylation, and olefination of C–H bonds within complex targets.

Rhodium(iii)-catalyzed intermolecular [3+3] annulation of benzoxazines with quinone compounds: access to spiro-heterocyclic scaffolds

“…Based on the above experimental results and literature precedents, 6 a plausible reaction mechanism is depicted in Scheme 6. First, active monomeric cationic Rh( iii ) species A was generated in the presence of Zn(OAc) 2 , which was then coordinated with the N-atom of benzoxazine 1a , followed by reversible C–H activation to generate a rhodacycle intermediate 15 .…”

“…On the other hand, transition metal-catalyzed C–H bond activation has become one of the hottest topics in synthetic organic chemistry for the construction of molecular complexity in a single step. 6 In particular, benzoxazines have attracted a great deal of attention in Rh( iii )-catalyzed C–H activation because the nitrogen atom could act as a good directing group (DG) in the process of formation of a key rhodacycle intermediate. 7 Recently, the Rh( iii )-catalyzed cascade C–H activation for spiroannulation and cyclization of benzoxazines with various coupling partners such as activated alkenes, 8 alkynes 9 and diazo ketoesters 10 a have been well established to construct a variety of cyclic five- and six-membered heterocyclic scaffolds (Scheme 1a).…”

Ruthenium(II)-Catalyzed Remote C–H Sulfonylation of 2-Pyridones

“…In the past two decades, metal-catalyzed C–H bond activation has been increasingly explored for the transformations of C–H bonds to C–C or C–heteroatom bonds . This strategy possesses a class-leading advantage over conventional approaches, which can avoid the preactivation step and afford a more straightforward approach to complex molecules . In this context, synthetic chemists have spared no efforts to focus on the direct C–H functionalization of 2-pyridones for the rapid access to densely substituted 2-pyridone cores .…”

Rh(III)-Catalyzed Dienylation and Cyclopropylation of 1,2,3-Benzotriazinones with Alkylidenecyclopropanes

“…Transition-metal-catalyzed C–H bond functionalization has become an attractive strategy for assembly of structurally diverse molecules in organic synthesis . 1,2,3-Benzotriazinones as important building blocks were frequently used in transition-metal-catalyzed C–H functionalization reactions over the past years (Scheme a).…”