A Chiral Nitrogen Ligand for Enantioselective, Iridium‐Catalyzed Silylation of Aromatic C−H Bonds

Abstract

Iridium catalysts containing dative nitrogen ligands are highly active for the borylation and silylation of C-H bonds, but chiral analogs of these catalysts for enantioselective silylation reactions have not been developed. We report a new chiral pyridinyloxazoline ligand for enantioselective, intramolecular silylation of symmetrical diarylmethoxy diethylsilanes. Regioselective and enantioselective silylation of unsymmetrical substrates was also achieved in the presence of this newly developed system. Preliminary mechanistic studies imply that C-H bond cleavage is irreversible, but not the rate-determining step. Iridium works nowA new chiral pyridinyloxazoline ligand was developed, which enables enantioselective, intramolecular silylation of symmetrical diarylmethoxy diethylsilanes. Regioselective and enantioselective silylation of unsymmetrical substrates was also achieved in the presence of this newly developed system.Correspondence to: John F. Hartwig; Zhang-Jie Shi. Supporting information for this article is given via a link at the end of the document.((Please delete this text if not appropriate)) Arylsilanes are important in material science [1] and are valuable synthetic intermediates in agroscience, [2] and medicinal chemistry. [3] Among the various reactions that form C-Si bonds, [4] transition metal-catalyzed direct silylation of inert C-H bonds has been a target because of the potential of this reaction to generate organosilanes under mild and neutral conditions from readily available starting materials. [5] The resulting C-Si bond can be transformed to a variety of carbon-carbon and carbon-heteroatom bonds. [5a, 6] Although various enantioselective, transition metal-catalyzed C-H bond functionalizations have been developed, enantioselective silylations are rare, [7] and all of the current, enantioselective silylations of aromatic C-H bonds have been conducted with rhodium catalysts and a diene or a diphosphine ligand. In 2013, Takai, Kuninubu, and coworkers reported the first enantioselective silylation of aromatic C-H bonds. This reaction produced chiral spirosilabifluorene derivatives, but with an ee of only 81% (Scheme 1a, left). [8] In 2015, Shibata, He, and Takai independently reported enantioselective silylations of C-H bonds in ferrocenes catalyzed by rhodium complexes containing diene or diphosphine ligands (Scheme 1a, middle). [8b, 9] Recently, one of our groups reported enantioselective silylations of aryl C-H bonds with ee values of 72 to 99% catalyzed by rhodium complexes ligated by chiral diphosphines (Scheme 1a, right). [10] Iridium catalysts containing bipyridine and phenanthroline ligands enable the silylation of C-H bonds with the most favorable combination of rate and functional-group compatibility, but the planar structure of the ligand makes the development of chiral iridium catalysts for enantioselective silylation particularly challenging to develop. To create chiral iridium catalysts for the silylation of C-H bonds, we investigated complexes containing chiral, ...

Recent Progress in Transition Metal‐Catalyzed Hydrosilane‐Mediated C−H Silylation

“…The authors revealed that the system composed of iridium/ligand L 3 enabled highly enantioselective silylation of diarylmethanols to form cyclic silyl ethers in good to excellent yields with high enantioselectivity (Scheme 9(a)). [11] A proposed mechanism to consistent with the experimental results was presented in Scheme 9(b). A active Ir I À H species was generated in situ in the presence of precursor [Ir(cod)OMe] dimer, pyridinyloxazoline and monohydrosilane, followed by coordination and insertion of norbornene to form int II.…”

“…In order to overcome the drawbacks of the above system, Hartwig and Shi group developed a new type of iridium/pyridinyloxazoline catalytic system, which overcame the drawbacks of previous work. The authors revealed that the system composed of iridium/ligand L 3 enabled highly enantioselective silylation of diarylmethanols to form cyclic silyl ethers in good to excellent yields with high enantioselectivity (Scheme 9(a)) [11] …”

Development and Scale-Up of Stereoretentive α-Deuteration of Amines

“…Among all isotopes used to this end, deuterium plays a key role . Indeed, deuterium is not a radioactive nucleus like 3 H and 14 C, and it is less expensive than 13 C and 15 N. The versatility of deuterium-labeled molecules has been demonstrated in a wide range of applications, from proteomics, metabolomics, medical imaging, and drug discovery to tools for mechanistic investigations of bio-organic and organic reactions . In recent years, the demand for deuterium-labeled molecules has also increased due to the development of quantitative mass spectrometry analysis .…”

Iridium-Catalyzed, β-Selective C(sp3)–H Silylation of Aliphatic Amines To Form Silapyrrolidines and 1,2-Amino Alcohols

“…To develop a catalyst for the site-selective and enantioselective silylation, 11d23 of unactivated C(sp 3 )-H bonds of aliphatic amines, iridium complexes of a variety of chiral N,N -ligands were investigated as catalysts for the silylation of amine 2a (Table 4). An initial survey with chiral, nitrogen-based ligands that are commonly used in asymmetric catalysis, such as bis(oxazoline) ligands (e.g., L7 , entry 1) and pyridyl oxazoline ligands (e.g., L8 , entry 2) that formed highly enantioselective catalysts in our prior silylation of both C(sp 2 )-H and C(sp 3 )-H bonds, 23e23f showed that the reactivity and enantioselectivity of catalysts formed from these common classes of chiral N,N -based structures were low.…”