Chiral Imidazo[1,5-a]pyridine–Oxazolines: A Versatile Family of NHC Ligands for the Highly Enantioselective Hydrosilylation of Ketones

Abstract

Herein we report the synthesis and application of a versatile class of N-heterocyclic carbene ligands based on an imidazo­[1,5-a]­pyridine-3-ylidine backbone that is fused to a chiral oxazoline auxiliary. The key step in the synthesis of these ligands involves the installation of the oxazoline functionality via a microwave-assisted condensation of a cyano-azolium salt with a wide variety of 2-amino alcohols. The resulting chiral bidentate NHC-oxazoline ligands form stable complexes with rhodium­(I) that are efficient catalysts for the enantioselective hydrosilylation of structurally diverse ketones. The corresponding secondary alcohols are isolated in good yields (typically >90%) with good to excellent enantioselectivities (80–93% ee). The reported hydrosilylation occurs at ambient temperatures (40 °C), with excellent functional group tolerability. Even ketones bearing heterocyclic substituents (e.g., pyridine or thiophene) or complex organic architectures are hydrosilylated efficiently, which is discussed further in this report.

Direct Asymmetric Hydrogenation and Dynamic Kinetic Resolution of Aryl Ketones Catalyzed by an Iridium‐NHC Exhibiting High Enantio‐ and Diastereoselectivity

“…In contrast to our previously reported hydrosilylation, catalyst 5 a is also able to hydrogenate quite sterically demanding aryl ketones such as propiophenone, 2‐cyclopropylphenyl ketone, and 2,2‐dimethylpropiophenone (Scheme ; 6 o – 6 q ). Moreover, under the here reported reaction conditions ketones are preferentially hydrogenated over alkenes (Scheme , 6 r ), although α,β‐substituted ketones give an intractable mixture of products.…”

“…We reasoned that a strategy including oxazolines would facilitate efficient transfer of the catalyst chiral topology to the pro‐chiral substrate. Indeed our recently developed chiral imidazo[1,5‐a]pyridine‐oxazoline ligands facilitated the rhodium catalyzed hydrosilylation of ketones with good enantioselectivities (up to 95 % ee ) . Encouraged by these results, we envisioned that these ligands might also provide unprecedented reactivity in direct asymmetric hydrogenation of aryl ketones.…”

“…Our initial investigation started with the synthesis of new iridium complexes ( 5 a – 5 d ), according to our previously reported synthetic methodology . We have updated our methodology to include a salt metathesis with sodium tetrakis[3,5‐bis(trifluoromethyl)phenyl]‐borate (NaBArF 24 ), to increase the solubility of our complexes in nonpolar solvents (Scheme ).…”

Enantioselective Hydroboration of Styrenes with Markovnikov Selectivity Catalyzed by a Rhodium(I)-NHC Complex

“…Drawing from our previous experience with similar chiral ligand systems, we began our initial optimization with styrene as a model substrate, pinacolborane (HBpin) as a borane source, and rhodium complex 5a (2 mol %) as a catalyst in dichloromethane (1 mL). Gratifyingly, stirring the reaction mixture for 18 h at room temperature afforded the corresponding boronic ester in 99% yield (NMR) with a regioselectivity 69:31 branched vs linear (b:l).…”

“…Recently, we reported chiral rhodium and iridium complexes based on a imidazo­[1,5- a ]­pyridine-oxazoline platform inspired by the design principles developed by Burgess et al, Glorius et al., and Lassaletta et al These complexes were used for the enantioselective hydrosilylation, and hydrogenation of ketones with moderate to good enantioselectivity . In order to improve the overall enantioselective induction in our previously reported imidazo­[1,5- a ]­pyridine-oxazoline platforms, we sought to introduce a second chiral substituent on the imidazo­[1,5- a ]­pyridine backbone, inspired by the chiral induction of the bulky 1-(naphthalen-1-yl)­ethyl substituent in Hermann’s Rhodium and Glorius’s ruthenium monodendate NHC catalysts …”