Native functional group directed distal C(sp³)–H activation of aliphatic systems

Abstract

Aliphatic systems are ubiquitous in numerous natural products and pharmacoactive compounds. Selective remote C-H functionalization of such aliphatic chains is of great significance and remains a challenge to be addressed....

Palladium-Catalyzed Annulations via Sequential C–H Activations of C(sp2)–H/C(sp3)–H or C(sp3)–H/C(sp3)–H Bonds

“…Notably, there has been an increasing number of C–H activation-based annulation methodologies, which underscores the considerable potential of C–H functionalization approaches to access complex molecular architectures . When contrasted with conventional metal-catalyzed annulation reactions such as cross-couplings or trimethylenemethane (TMM) based cycloadditions, C–H activation approaches often take advantage of the scaffold’s native functionalities to co-opt otherwise inert C–H bonds and utilize them toward the construction of cyclic ring systems . Consequently, by avoiding potentially lengthy prefunctionalized substrate syntheses, C–H activation approaches can greatly simplify synthetic access to ring-containing pharmaceuticals and bioactive compounds …”

Iodoarene-directed photoredox β-C(sp3)–H arylation of 1-(o-iodoaryl)alkan-1-ones with cyanoarenes via halogen atom transfer and hydrogen atom transfer

“…Site selective functionalization of inert C(sp 3 )–H bonds for targeted increase of molecular complexity and upgrading abundant hydrocarbon feedstocks into value-added compounds represents a prominent theme in chemistry. 1–3 In the field, direct C(sp 3 )–H arylation of saturated carbonyl compounds, such as ketones, amides, aldehydes, esters and acids, has been recognized as one of the most powerful methodologies for the site selective incorporation of an aryl functionality into the alkyl chain to construct a wealth of biologically relevant aryl motif-containing molecules and synthetic intermediates. 2,3 In contrast to the well-explored arylation of C(sp 3 )–H bonds at the α-position in carbonyl compounds, 1,2 direct arylation of C(sp 3 )–H bonds at the β-position or at remote positions in the carbonyl compounds is largely underdeveloped and remains a great challenge in site selectivity control due to the competitive reactions, such as the more acidic α-C(sp 3 )–H bond arylation.…”

“…1–3 In the field, direct C(sp 3 )–H arylation of saturated carbonyl compounds, such as ketones, amides, aldehydes, esters and acids, has been recognized as one of the most powerful methodologies for the site selective incorporation of an aryl functionality into the alkyl chain to construct a wealth of biologically relevant aryl motif-containing molecules and synthetic intermediates. 2,3 In contrast to the well-explored arylation of C(sp 3 )–H bonds at the α-position in carbonyl compounds, 1,2 direct arylation of C(sp 3 )–H bonds at the β-position or at remote positions in the carbonyl compounds is largely underdeveloped and remains a great challenge in site selectivity control due to the competitive reactions, such as the more acidic α-C(sp 3 )–H bond arylation. 3–6 Typically, transition-metal-catalyzed chelation-assisted β-C(sp 3 )–H arylation reactions as reliable methods for producing β-aryl carbonyl systems have been intensively developed, where the vast majority of which concerned directing group (DG)-possessing amides, 3,4 a – d and ketones/aldehydes (using amino-acid based transient directing groups).…”

Directed C(sp3)-H Arylation of Free α-Aminophosphonates: Dual Models Exploration via Palladium Catalysis

“…Recently, Yu, Ge, Dong, Murakami, Bull, Young, and others have successfully achieved C–H bond activation of aliphatic amines and amino acids through TDGs copalladium catalysis . Furthermore, the free amino group itself works in synergy with palladium to accomplish C­(sp 3 )-H functionalization of aliphatic amine and amino acid side chains . In this strategy, Gaunt, Yu, Li, and Jiao achieved a series of breakthroughs in the C–H bond activation of aliphatic amines through ligand modulation .…”