[Retracted] Enantioselective Rh- or Ir-catalyzed Directed C(sp³)–H Borylation with Phosphoramidite Chiral Ligands

Abstract

Enantioselective heteroatom-directed C(sp 3 )H borylation reactions of 2-aminopyridines and 2-alkylpyridines with Rh-and Ir catalytic systems using commercially available chiral monophosphine ligands, respectively, were developed. This methodology provides an innovative example of a homogeneous catalytic system for C(sp 3 )H borylation, and allows the direct synthesis of optically active alkylboronates with a moderate level of enantioselectivity. Keywords: C-H activation | Borylation | Asymmetric catalysisThe synthesis of highly functionalized molecules via the direct and selective transformation of CH bonds is a highly attractive strategy and a fundamental frontier in organic synthesis. CH bond activation strategies in transition metal catalysis have become one of the most expedient and powerful tools in molecular diversification.1,2 While there has been significant progress in the direct transformation of C(sp 2 )H bonds, the functionalization of C(sp 3 )H bonds remains challenging due to both the absence of π-orbitals that can interact with a transition metal and the sterically demanding geometry of C(sp 3 )H bonds compared to planar C(sp 2 )H bonds. Moreover, enantioselective C(sp 3 )H functionalization contributing to an efficient access to optically active molecules is underdeveloped. Recently, our group reported the heteroatom-directed borylation of C(sp 3 )H bonds with heterogeneous Rh-and Ircatalyst systems based on silica-supported bridgehead monophosphines, Silica-SMAP and Silica-TRIP. 46 This strategy allowed site-selective borylation of the N-adjacent or unactivated C(sp 3 )H bonds located γ to N or O atoms in the directing groups due to the proximity effects by the heteroatom-to-metal coordination. We next turned our attention to develop their enantioselective versions to give optically active alkylboronates.7 Along this line, however, the structural modification of the silica-supported caged phosphines aiming to the asymmetric reactions would be challenging. On the basis of our knowledge that the controlled mono-P-ligation toward metals is crucial, 8 we thought to use appropriate soluble ligands to realize the heteroatom-directed C(sp 3 )H borylation. 9 This protocol can open a synthetic opportunity to explore and extend the borylation reactions under homogeneous catalysis. 10Herein, we report the Rh-or Ir-catalyzed site-selective C(sp 3 )H borylation of 2-aminopyridines and 2-alkylpyridines providing an innovative example of a homogeneous catalytic system. The use of a readily available chiral phosphoramidite as a ligand allows the direct synthesis of optically active alkylboronates with moderate level of enantioselectivity.Initially, to investigate the possibility of catalytic borylation using homogeneous ligands, our studies commenced by using 2-(pyrrolidine-1-yl)pyridine (1a) as the substrate towards Rhcatalyzed N-adjacent C(sp 3 )H borylation using bis(pinacolato)-diboron (2, 1.25 equiv) (Scheme 1). The reaction was conducted in CPME at 60°C over 15 h in the presence of [Rh(OH)(cod)] 2 (2 mo...

Iridium‐Catalyzed Enantioselective C(sp3)–H Borylation of Cyclobutanes

“…Rh‐ and Ir‐catalyzed asymmetric C—H borylation has emerged as a viable approach to access optically active organoboron compounds in an atom‐ and step‐economic way under mild reaction conditions. [ 18 ] However, it is still subjected to limitations such as the reaction types. Recently, we reported the amide‐directed Ir‐catalyzed enantioselective C(sp 3 )–H borylation of cyclopropanes using chiral bidentate boryl ligands.…”

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

“…Following the reported heteroatom-directed borylation of C(sp 3 )-H bonds with Rh-and Ircatalyst systems based on heterogeneous immobilized silica-supported bridgehead monophosphine, Silica-SMAP and Silica-TRIP, by Sawamura and co-workers (see Figures 42-46) several homogeneous monophosphines were observed to also promote the challenging C(sp 3 )-H borylation. For example, the borylation of 2-aminopyridine derivatives with bis(pinacolatodiboron) under rhodium catalysis gave the corresponding secondary -aminoboronate with the sterically hindered P(o-tol)3 and P(tBu)3 identified to be the most effective ligands (Reyes, Harada, et al, 2017). These results open a synthetic opportunity to extend the reaction protocol to a catalytic asymmetric technique to directly synthesize enantioenriched alkylboronates from functionalized alkanes.…”

Novel Chiral Ligands‐Enabled Transition‐Metal‐Catalyzed Asymmetric C—H Borylation

“…The asymmetric discrimination of unactivated enantiotopic methylene C—H bonds is a long‐standing challenge in organic synthesis. In 2017, Sawamura group reported that the chiral monophosphoramidite ligands could promote the borylation of methylene C(sp 3 )—H bonds with moderate enantioselectivities . After an extensive optimization of the catalysts, they disclosed an iridium‐catalyzed asymmetric borylation of unactivated methylene C(sp 3 )—H bonds in 2‐alkylpyridines and 2‐alkylazole derivatives by using the 1,1'‐Bi‐2‐naphthol (BINOL)‐based chiral monophosphite ligand L1 (Scheme ) .…”