Directional Ionic Bonds

Covalent and ionic bonds represent two fundamental forms of bonding between atoms. In contrast to bonds with significant covalent character, ionic bonds are of limited use for the spatial structuring of matter because of the lack of directionality of the electric field around simple ions. We describe a predictable directional orientation of ionic bonds that contain concave nonpolar shields around the charged sites. Such directional ionic bonds offer an alternative to hydrogen bonds and other directional noncovalent interactions for the structuring of organic molecules and materials

Site‐Selective C−H Arylation of Diverse Arenes Ortho to Small Alkyl Groups

Catalytic systems for direct C−H activation of arenes commonly show preference for electronically activated and sterically exposed C−H sites. Here we show that a range of functionally rich and pharmaceutically relevant arene classes can undergo site-selective C−H arylation ortho to small alkyl substituents, preferably endocyclic methylene groups. The C−H activation is experimentally supported as being the selectivity-determining step, while computational studies of the transition state models indicate the relevance of non-covalent interactions between the catalyst and the methylene group of the substrate. Our results suggest that preference for C(sp2)−H activation next to alkyl groups could be a general selectivity mode, distinct from common steric and electronic factors

Direct C–H Arylation

Bonds between hydrogen and carbon atoms are the most frequent type of bonds in organic molecules. The ability to replace hydrogen atoms by making other types of bonds to carbon atoms can enable simpler access to complex organic molecules by substituting multistep synthetic sequences. The use of transition metal catalysts to activate C–H bonds is particularly attractive as it offers control over the reactivity and selectivity through catalyst design. However, such functionalization includes the difficult breaking of strong C–H bonds that are not activated by the presence of other groups. Additionally, the common presence of a number of C–H bonds in a molecule raises the issue of site-selectivity because differentiation of C–H bonds that are in sterically and electronically similar environments is a challenge. We discuss selected recent developments that are a part of the long-term research interest in mild and selective C–H activation reactions with a focus on the replacement of C–H bonds with C–aryl groups and an emphasis on the work of our group

Introduction to Spatial Anion Control for Direct C–H Arylation

C–H activation of functionally rich molecules without the need for directing groups promises shorter organic syntheses and late-stage diversification of molecules for drug discovery. We highlight recent examples of palladium-catalyzed nondirected functionalization of C–H bonds in arenes as limiting substrates with a focus on the development of the concept of spatial anion control for direct C–H arylation. 1 C–H Activation and the CMD Mechanism 2 Nondirected C–H Functionalizations of Arenes as Limiting Substrates 3 Nondirected C–H Arylation 4 Spatial Anion Control for Direct C–H Arylation 5 Coordination Chemistry with Spatial Anion Control 6 Conclusio

Spatial Anion Control on Palladium for Mild C–H Arylation of Arenes

C–H arylation of arenes without the use of directing groups is a challenge, even for simple molecules, such as benzene. We describe spatial anion control as a concept for the design of catalytic sites for C–H bond activation, thereby enabling nondirected C–H arylation of arenes at ambient temperature. The mild conditions enable late-stage structural diversification of biologically relevant small molecules, and site-selectivity complementary to that obtained with other methods of arene functionalization can be achieved. These results reveal the potential of spatial anion control in transition-metal catalysis for the functionalization of C–H bonds under mild conditions