Borylation and Silylation of C–H Bonds: A Platform for Diverse C–H Bond Functionalizations

Abstract

Methods that functionalize C-H bonds can lead to new approaches for the synthesis of organic molecules, but to achieve this goal, researchers must develop site-selective reactions that override the inherent reactivity of the substrates. Moreover, reactions are needed that occur with high turnover numbers and with high tolerance for functional groups if the C-H bond functionalization is to be applied to the synthesis of medicines or materials. This Account describes the discovery and development of the C-H bond functionalization of aliphatic and aromatic C-H bonds with borane and silane reagents. The fundamental principles that govern the reactivity of intermediates containing metal-boron bonds are emphasized and how an understanding of the effects of the ligands on this reactivity led us to broaden the scope of main group reagents that react under mild conditions to generate synthetically useful organosilanes is described. Complexes containing a covalent bond between a transition metal and a three-coordinate boron atom (boryl complexes) are unusually reactive toward the cleavage of typically unreactive C-H bonds. Moreover, this C-H bond cleavage leads to the formation of free, functionalized product by rapid coupling of the hydrocarbyl and boryl ligands. The initial observation of the borylation of arenes and alkanes in stoichiometric processes led to catalytic systems for the borylation of arenes and alkanes with diboron compounds (diborane(4) reagents) and boranes. In particular, complexes based on the Cp*Rh (in which Cp is the cyclopentadienyl anion) fragment catalyze the borylation of alkanes, arenes, amines, ethers, ketals, and haloalkanes. Although less reactive toward alkyl C-H bonds than the Cp*Rh systems, catalysts generated from the combination of bipyridines and iridium(I)-olefin complexes have proven to be the most reactive catalysts for the borylation of arenes. The reactions catalyzed by these complexes form arylboronates from arenes with site-selectivity for C-H bond cleavage that depends on the steric accessibility of the C-H bonds. These complexes also catalyze the borylation of heteroarenes, and the selectivity for these substrates is more dependent on electronic effects than the borylation of arenes. The products from the borylation of arenes and heteroarenes are suitable for a wide range of subsequent conversions to phenols, arylamines, aryl ethers, aryl nitriles, aryl halides, arylboronic acids, and aryl trifluoroborates. Studies of the electronic properties of the ancillary ligand on the rate of the reaction show that the flat structure and the strong electron-donating property of the bipyridine ligands, along with the strong electron-donating property of the boryl group and the presence of a p-orbital on the metal-bound atom, lead to the increased reactivity of the iridium catalysts. Based on this hypothesis, we studied catalysts containing substituted phenanthroline ligands for a series of additional transformations, including the silylation of C-H bonds. A sequence involving the silylat...

Rhodium‐Catalyzed Enantioselective Silylation of Cyclopropyl C−H Bonds

“…[1,2] However, the development of enantioselective variants of these reactions, particularly enantioselective functionalization of alkyl C-H bonds, has been limited (Scheme 1). [3][4][5] Kuninobu, Murai and Takai reported the Correspondence to: John F. Hartwig, jhartwig@berkeley.edu.…”

“…[27,29] Silyl ether 2a formed by the Ru-catalyzed process was used without further purification for the silylation of a cyclopropyl C-H bond after the removal of the solvent and remaining diethylsilane. (1) Having identified a simple synthesis of 2a, we sought conditions for the asymmetric, intramolecular silylation (Table 1). Based on previous reports of Rh-catalyzed silylations of C-H bonds, [9][10][11][12] we examined the Rh catalyst derived from [Rh(cod)Cl] 2 and (S)-DTBM-SEGPHOS (L1) with cyclohexene as a hydrogen acceptor [30] at 80 °C (entry 1).…”

Totalsynthese von Nosiheptid

“…Basierend auf Literaturbeispielen zur meta-selektiven Borylierung von Pyridinen [283][284][285][286][287] mittels Ir-katalysierter C-H-Aktivierung [288][289][290] Die Ausbeute an Pyridin 233 lag jedoch bei nur 20% über zwei Stufen und bedarf weiterer…”

Diborane heterolysis: breaking and making B–B bonds at magnesium

“…The resultant C-B bonds provide a straightforward means to introduce further functionality, either through oxidation or their use in catalytic C-C bond formation through the application of Suzuki-Miyaura protocols. [1][2][3] Boryl moieties are conventionally transferred to an organic substrate by a variety of routes (e.g. alkene hydroboration) which are reliant upon the Lewis acidic and electrophilic behaviour of the electropositive boron centre in reaction with an organic nucleophile.…”