Iridium‐Catalyzed Enantioselective Unbiased Methylene C(sp³)–H Borylation of Acyclic Amides

Abstract

We herein report amide directed enantioselective β‐C(sp3)−H borylation of unbiased methylene C−H bonds of acyclic amides enabled by iridium catalysis for the first time. The key to the success of this transformation relies on the careful selection of the combination of iridium precursor and chiral bidentate boryl ligands. A variety of functional groups are well‐tolerated, affording chiral β‐functionalized amides in good to excellent enantioselectivities. We also demonstrate the application of the current method by stereospecific conversion of C−B bond into other functionalities.

Coordination-assisted, transition-metal-catalyzed enantioselective desymmetric C–H functionalization

“…In 2021, they successfully applied this type of ligand in the carbonyl-directed enantioselective borylation of unbiased methylene C(sp 3 )-H bond of acyclic amides (Scheme 40a). 84 A variety of functional groups were well tolerated, affording the borylated amides in good to excellent enantioselectivities. Very recently, the Xu group reported a pyrazole-directed Ir(I)-catalyzed enantioselective β-borylation of unbiased methylene C(sp 3 )-H bonds (Scheme 40b).…”

Asymmetric C(sp3)–H borylation: an update

“…In the same year, Xu’s group 32 reported the Ir-catalyzed amide-directed enantioselective β-C(sp 3 )–H borylation of readily available acyclic amides using modified chiral borylated ligands (CBL). As displayed in Scheme 13, acyclic amides ( 13a , 0.2 mmol) were reacted with bis(pinacolato)diboron (0.3 mmol) and [IrCl(cod)] 2 (2.5 mol%) in n -hexane (2.0 mL) over the thermal range of 60–80 °C for 20–48 hours; a sequential oxidation was also carried out in the presence of alkaline H 2 O 2 at room temperature for 4 hours, which ultimately provided the desired enantioselective product 13b in good yield.…”

An Introductory Overview of C–H Bond Activation/ Functionalization Chemistry with Focus on Catalytic C(sp3)–H Bond Borylation

“…In their work, the careful selection of iridium precursors and chiral bidentate boryl ligands (CBL) proved crucial in allowing a variety of C-H bond borylation encompassing different but complementary substrate classes to that reported by Yu and Sawamura. For example, the strategy can target C(sp 3 )-H bonds in cyclopropanes (Shi et al, 2019) and cyclobutanes , -C(sp 3 )-H bonds of azacycles (Chen, Yang et al, 2020), and unbiased methylene C-H bonds of acyclic amides (Yang et al, 2021) giving the corresponding boronates with excellent enantioselectivities. Remote C(sp 3 )-H bond functionalization chemistry (Qiu and Wu, 2015;Sharma, 2018) has progressed slowly compared to the activation and subsequent transformation of remote C(sp 2 )-H bonds (see: Ali and Siddiqui, 2021;Genov et al, 2020;Lu et al, 2019;Kuninobu et al, 2015).…”