Sterically Directed Functionalization of Aromatic C−H Bonds:  Selective Borylation Ortho to Cyano Groups in Arenes and Heterocycles

Abstract

Ir-catalyzed borylations of 4-substituted benzonitriles are described. In contrast to electrophilic aromatic substitutions and directed ortho metalations, C-H activation/borylation enables functionalization at the 2-position, adjacent to the cyano group, when the 4-subsitutent is larger than cyano. When an excess of borane reagent is used, diborylation can be achieved with a single regioisomer being formed in certain cases. Extension of sterically directed borylation to cyano-substituted, five- and six-membered ring heterocycles is also reported.

Iridium-catalyzed borylation of thiophenes: versatile, synthetic elaboration founded on selective C–H functionalization

“…3-Cyanothiophene gave the poorest regioselectivity with 2-borylated product 7b being the major isomer. While CN is one of the smallest substituents, previous work shows that borylation ortho to H is preferred relative to CN for arenes, 37 and the results for entry 1 are the first where borylation ortho to CN appears to be favoured. Contrary to a literature report noting its instability, 36 7b was sufficiently stable to be persistent in the isolated isomer mixture.…”

“…However, selectivities will likely be lower than those for arenes since the distance between neighbouring substituents increases as the number of ring atoms decreases. 37 Indeed, some of these expectations are born by the data in Table 2. In cases where isomer mixtures resulted (Table 2 entries 1-4 and 8) 2.0 equiv of thiophene was used to minimize losses arising from diborylation.…”

“…For these substrates, the 5-borylated isomers are the major products and the relative isomer ratios (a:b) for Cl, Br, and Me follow the trend seen in arenes. 37 For the pTol substituted substrate (entry 8) the selectivity is sufficiently high for 14a to be synthetically useful. As compared to Rh and Pd catalysts that favour borylation of benzylic C-H bonds, [38][39][40] Ir catalysts are highly selective for aromatic over benzylic C-H bond functionalization, 27,28 even for substrates with hindered arene C-H bonds like p-xylene.…”

Recent progress in the synthesis of pyridinylboronic acids and esters

“…Two main types of ligand are reported in the literature for the synthesis of pyridinylboronic acids esters: bipyridine compounds (14a-d) and pyridinylimine compounds (15a, b). [67][68][69][70][71][72][73][74][75] 2.4.2. The regioselectivity of the iridium-or rhodium-catalyzed C-H bond borylation.…”

“…In general, the 2,6-disubstituted pyridine gave only 4-pyridinylboronic esters, while pyridine or monosubstituted pyridines gave a mixture of 3-and 4-pyridinylboronic esters. [73][74][75] The borylation selectivity with ligands 14b and 14d were observed to be different: borylation occurred in the position adjacent to the nitrogen atom in 14b ( R = tBu), but occurred at the 5-position (i.e. ortho to the methoxy groups) in 14d (R = OMe).…”