Iridium‐Catalyzed Ligand‐Controlled Remote para‐Selective C−H Activation and Borylation of Twisted Aromatic Amides

Abstract

A method of para‐selective borylation of aromatic amides is described. The borylation proceeded via an unprecedented substrate–ligand distortion between the twisted aromatic amides and a newly designed ligand framework (defa) that is different from the traditionally used ligand (dtbpy) for the C−H borylation reactions. The designed ligand framework (defa) has led to the development of a new type of catalytic system that shows excellent para selectivity for a range of aromatic amides. Moreover, the designed ligand has shown excellent reactivity and selectivity for a range of heterocyclic aromatic amides. The identification of key transition states and intermediates using the DFT computations associated with the three regio‐isomeric pathways revealed that the most efficient catalytic pathway with the defa ligand leads to the para borylation while in the case of bpy the borylation at the para and meta sites compete.

N-oxide ligands for selective separations of lanthanides: insights from computation

“…It starts with a commercially available compound, 3-methyl-1,8-naphthyridine-2-carboxylic acid ( 1 ), which reacts with methyllithium to yield 2 , 33 followed by oxidation to 3 . 34 Equivalent 3 and 2-aminonicotinaldehyde react in potassium hydroxide and ethanol to yield 4 , 35 which dehydrates in polyphosphoric acid (PPA) to yield 5 , 36 followed by hydrazine reduction to 6 . 36 Finally, 6 can be selectively oxidized by reacting with 3.5 equivalent meta -chloroperoxybenzoic acid ( m CPBA) in dichloromethane, 37 to yield 2b .…”

“…34 Equivalent 3 and 2-aminonicotinaldehyde react in potassium hydroxide and ethanol to yield 4 , 35 which dehydrates in polyphosphoric acid (PPA) to yield 5 , 36 followed by hydrazine reduction to 6 . 36 Finally, 6 can be selectively oxidized by reacting with 3.5 equivalent meta -chloroperoxybenzoic acid ( m CPBA) in dichloromethane, 37 to yield 2b . Similar routes can also be adopted to synthesize 3a and 3b .…”

C–H borylation: a tool for molecular diversification

“…A highly para -selective C–H bond activation and borylation of aromatic amides was developed by our group 122 using a newly designed ligand framework (defa; 1 st generation, L6 ) where unprecedented substrate–ligand distortion between the twisted aromatic amides and ligand controlled the regioselectivity (Fig. 40).…”

Transition-Metal-Catalyzed Silylation and Borylation of C–H Bonds for the Synthesis and Functionalization of Complex Molecules

“…In 2022, Sunoj and Chattopadhyay et al published paraselective, iridium-catalyzed borylations of aryl C−H bonds on twisted amides catalyzed by iridium and a 4,5-diazafluorene (defa) (Scheme 76). 137 Computational evidence suggests the intervening methylene on the ligand causes an in-plane distortion, which leads to a steric interaction between the ligand and the twisted amide on the substrate. The interaction is minimized by the approach of the substrate at its para position.…”