Iridium‐Catalyzed Silylation of Five‐Membered Heteroarenes: High Sterically Derived Selectivity from a Pyridyl‐Imidazoline Ligand

Abstract

The steric effects of substituents on five‐membered rings are less pronounced than those on six‐membered rings because of the difference in bond angles. Thus, the regioselectivities of reactions of five‐membered heteroarenes that occur with selectivities dictated by steric effects, such as the borylation of C−H bonds, have been poor in many cases. We report that the silylation of five‐membered‐ring heteroarenes occurs with high sterically derived regioselectivity when catalyzed by the combination of [Ir(cod)(OMe)]2 (cod=1,5‐cyclooctadiene) and a phenanthroline ligand or a new pyridyl‐imidazoline ligand that further increases the regioselectivity. The silylation reactions with these catalysts produce high yields of heteroarylsilanes from functionalization at the most sterically accessible C−H bonds of these rings under conditions that the borylation of C−H bonds with previously reported catalysts formed mixtures of products or products that are unstable. The heteroarylsilane products undergo cross‐coupling reactions and substitution reactions with ipso selectivity to generate heteroarenes that bear halogen, aryl, and perfluoroalkyl substituents.

Sterically Controlled C−H Olefination of Heteroarenes

“…[13,14] This is well reflected in methods for the functionalization of thiophenes with an electronwithdrawing group in the 3-position. [6][7][8] Ty pical reports,especially concerning CÀCbond-forming reactions such as arylations, [8] describe the preferential substitution in the C2-position. Thef unctionalization in the C5-position has been achieved through indirect routes, [8c] on multiply substituted substrates, [7e] and in the case of sterically controlled borylations and silylations, [6] where catalysts are known not to be susceptible to directing effects.Furthermore, Sharp and co-workers described ac ase of the catalystcontrolled switch between C2-and C5-selective arylation, albeit using an excess of the heteroarene substrate.…”

“…[6][7][8] Ty pical reports,especially concerning CÀCbond-forming reactions such as arylations, [8] describe the preferential substitution in the C2-position. Thef unctionalization in the C5-position has been achieved through indirect routes, [8c] on multiply substituted substrates, [7e] and in the case of sterically controlled borylations and silylations, [6] where catalysts are known not to be susceptible to directing effects.Furthermore, Sharp and co-workers described ac ase of the catalystcontrolled switch between C2-and C5-selective arylation, albeit using an excess of the heteroarene substrate. [8b] The olefination of such substrates has been achieved with excellent selectivities for the C2-position by using the electron-withdrawing group as DG, [7] but no general method has been described that would allow the selective olefination of such substrates in the C5-position.…”

“…[3] In the CÀHa ctivation/functionalization of 3-substituted five-membered heteroarenes,such as thiophenes,furans,and pyrroles,t he differentiation between the C2 and C5 position constitutes ap rototypical example of such as electivity challenge. [4][5][6][7][8][9][10][11][12] Amongst other transformations, [5,6,8,10,12] the olefination of such substrates has raised significant interest (Scheme 1). [4,7,9,11] Thes ite selectivity of the CÀHa ctivation of 3-substituted five-membered heteroarenes is characterized by acompetition between effects favoring different positions in these substrates.F or substrates bearing electron-donating substituents in the 3-position, the C À Ha ctivation in the C2position is electronically favored, since the employed catalysts are typically electrophilic in nature and thus favor the activation in the most electron-rich position.…”

C(sp2)−Si Bond Functionalization through Intramolecular Activation by Alkoxides

“…Heteroarenes are ubiquitous units in organic compounds, and their regioselective functionalization is a fundamental endeavor for synthetic chemists [48] . In this context, the Brook rearrangement is a useful tool for this purpose, as shown by the several studies on intramolecular [1,4]‐C(sp 2 )→O silyl migrations of silylated furans and thiophenes.…”

Sterically Controlled C−H Olefination of Heteroarenes

“…Firstly, the angle between the substituent in 3‐position and the C2−H bond is larger than the one between a substituent on a six‐membered arene and the ortho ‐C−H bond. This reduces steric clash and thus renders steric control more challenging . Secondly, the heteroarenes employed as substrates and the respective products are substantially more reactive than typical arenes, leading to challenges such as overreaction and product decomposition, which in many studies have been compensated by using the heteroarene as excess component, but must be controlled to achieve useful yields in a heteroarene‐limited reaction.…”