Iridium‐Catalyzed Regio‐ and Enantioselective Borylation of Unbiased Methylene C(sp³)−H Bonds at the Position β to a Nitrogen Center

Abstract

Reported herein is the pyrazole‐directed iridium‐catalyzed enantioselective borylation of unbiased methylene C−H bonds at the position β to a nitrogen center. The combination of a chiral bidentate boryl ligand, iridium precursor, and pyrazole directing group was responsible for the high regio‐ and enantioselectivity observed. The method tolerated a vast array of functional groups to afford the corresponding C(sp3)−H functionalization products with good to excellent enantioselectivity.

On the application of 3d metals for C–H activation toward bioactive compounds: The key step for the synthesis of silver bullets

“…For instance, an intramolecular coupling of phenolic moieties using VOF 3 has been reported as a final step in the synthesis of the bioactive natural macrolactone (±)-decinine (30) (Scheme 11B) [96]. These compounds (26)(27)(28)(29) derive from the class of Lythraceae alkaloids (Scheme 11A), extracted from Heimia salicifolia, and present valuable pharmacological properties, such as antisyphilitic, sudoritic, antipyretic, laxative, and diuretic activities [97]. Trifluoroacetic acid was used as an additive, being suggested to avoid oxidation of the amine moiety by the formation of the corresponding ammonium salt.…”

“…One of the key synthetic methodologies is the C-H bond activation process that enables a straightforward access to several important and innovative compounds [14][15][16][17][18]. In the last few years, metals such as ruthenium [19][20][21], rhodium [22][23][24], palladium [25][26][27], and iridium [28][29][30] have been widely applied as catalysts for this matter, including in the synthesis of bioactive substances. Although catalysts based on these metals, are known to be efficient in C-H bond activation reactions affording the products in good yields and mild conditions, they are also known to be usually expensive.…”

Iridium‐Catalyzed Regio‐ and Enantioselective Borylation of Unbiased Methylene C(sp3)−H Bonds at the Position β to a Nitrogen Center

“…2]. [28] In summary, we have developed the CBL/Ir-catalyzed enantioselective borylation of unbiased methylene C(sp 3 )ÀH bonds at the position b to a nitrogen center using pyrazole as the directing group. A broad spectrum of functional groups could be well tolerated, affording a variety of b-functionalized chiral pyrazoles with good to excellent enantioselectivities under mild reaction conditions.…”

Development of a Tunable Chiral Pyridine Ligand Unit for Enantioselective Iridium-Catalyzed C–H Borylation

“…Recently, the Sawamura group disclosed a series of asymmetric borylation of methylene C–H bonds featuring a BINOL-derived phosphite-bound iridium catalyst . In a different line, Xu reported a set of chiral bidentate N,B-ligands containing a chiral diaminoborane skeleton for iridium-catalyzed asymmetric C­(sp 2 )–H and C­(sp 3 )–H borylation . In addition, Phipps demonstrated the meta -selective and enantioselective desymmetrization of geminal diaryl motifs by using ion-pairing interactions between a chiral cation and an anionic group linked to the bipyridine ligand .…”