Sequential Protocol for C(sp³)–H Carboxylation with CO₂: Transition-Metal-Catalyzed Benzylic C–H Silylation and Fluoride-Mediated Carboxylation

Abstract

One of the most challenging transformations in current organic chemistry is the catalytic carboxylation of a C(sp(3))-H bond using CO(2) gas, an inexpensive and ubiquitous C1 source. A sequential protocol for C(sp(3))-H carboxylation by employing a nitrogen-directed, metal-assisted, C-H activation/catalytic silylation reaction in conjunction with fluoride-mediated carboxylation with CO(2) was established. The carboxylation proceeded only at the benzylic C(sp(3))-Si bond, not at the aromatic C(sp(2))-Si, which is advantageous for further manipulations of the products.

Direct Carboxylation of C(sp3)-H and C(sp2)-H Bonds with CO2 by Transition-Metal-Catalyzed and Base-Mediated Reactions

“…In 2012, Sato published a sequential protocol for the selective "formal" carboxylation of benzylic C(sp 3 )-H bonds applied to substrates possessing a nitrogen directing group (Scheme 10) including substituted 8-methylquinoline, 2-(o-tolyl) pyridine, 2-(o-tolyl) pyrimidine and 2-(o-tolyl) quinoline (11 substrates, 29-90% yields) [75]. At first substrates were silylated with Et3SiH in toluene by Ru3(CO)12 catalyst according to the Kakiuchi protocol [76] to give benzylsilane derivatives 6 (Schemes 10a and 11a).…”

“…In 2012, Sato published a sequential protocol for the selective "formal" carboxylation of benzylic C(sp 3 )-H bonds applied to substrates possessing a nitrogen directing group (Scheme 10) including substituted 8-methylquinoline, 2-(o-tolyl) pyridine, 2-(o-tolyl) pyrimidine and 2-(o-tolyl) quinoline (11 substrates, 29-90% yields) [75].…”

Transition Metal-Catalyzed Carboxylation of Organic Substrates with Carbon Dioxide

“…Mita, Sato, and co-workers have recently disclosed the challenging carboxylation of benzylic C(sp 3 )-H bonds in sequential, one-pot protocols [168]. These ligand-free protocols involve the use of either Ir(I) or Ru(0) complexes such as [Ir(COD) 2 Cl] 2 and Ru 3 (CO) 12 in the presence of Et 3 SiH to enable an initial silylation of both C(sp 2 )-H and C(sp 3 )-H bonds of a tolyl ring system containing a pyridyl directing group.…”

Ruthenium-Catalyzed C–H Silylation of 1-Arylpyrazole Derivatives and Fluoride-Mediated Carboxylation: Use of Two Nitrogen Atoms of the Pyrazole Group

“…However, aromatic C(sp 2 )-Si bonds created as a side reaction in ruthenium catalysis remained intact even in the presence of an excess amount of fluoride. 4 Therefore, we next focused on how to promote the carboxylation of arylsilanes prepared from the corresponding arenes via C(sp 2 )-H bond silylation. Compared to fluoride-mediated carboxylation of C(sp 3 )-Si bonds with CO 2 , 6,7 carboxylation of arene C(sp 2 )-H bonds is relatively difficult since carboxylation is greatly influenced by the electronic property of the aromatic ring: Effenberger reported that electron-withdrawing ortho substituents of aryltrimethylsilanes (TMSAr), such as chloro and nitro groups, were necessary in order to promote the generation of an aryl carbanion prior to carboxylation with CO 2 .…”

“…Thus, we first screened potential catalysts for C(sp 2 )-H bond silylation using 1-(o-tolyl)pyrazole (1j) as a model substrate. According to the iridiumcatalyzed benzylic silylation developed by our group, 4 [Ir(cod)Cl] 2 was firstly employed under toluene reflux conditions without using a hydrogen-trapping reagent. As a result, the target ortho silylation product was obtained in 87% yield, but a small amount of the starting material remained ( Table 2, entry 1).…”