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

Abstract

of main observation and conclusion We herein report the first example of iridium-catalyzed enantioselective C(sp 3)-H borylation of cyclobutanes using benzoxazoline as the directing group. The combination of a chiral bidentate boryl ligand and an iridium precursor has found to effectively catalyze C(sp 3)-H borylation to afford a variety of cyclobutylboronates with good to excellent enantioselectivities. We also demonstrate the synthetic utility of the current method by converting the stereogenic C-B bond to other functionalities.

Catalytic enantioselective synthesis of benzocyclobutenols and cyclobutanols via a sequential reduction/C–H functionalization

“…Recently, the precision modification of four-membered ring skeletons to access enantioenriched cyclobutane derivatives has attracted emerging attention. Several strategies have been developed, including allylic alkylation, 8 α-functionalization, 9 conjugate addition 10 and C–H functionalization 11 of prochiral or racemic cyclobutane derivatives ( Scheme 2a ). 12 However, the enantioselective synthesis of chiral benzocyclobutene derivatives is still underdeveloped.…”

Development of Chiral Ligands for the Transition‐Metal‐Catalyzed Enantioselective Silylation and Borylation of C−H Bonds

“…For example, the ligand containing an N‐aryl group substituted with 2‐aryl and 5‐ t Bu substituents formed a catalyst that was both active and highly enantioselective for the borylation of cyclopropyl C−H bonds (Figure 25), [41a] while the catalyst containing the ligands bearing N‐aryl groups substituted with 2,6‐dimethyl or 2,6‐diethyl substituents reacted with higher enantioselectivity for the borylation of cyclobutyl C−H bonds (Figure 26). [41b] By further modification of the N,B‐ligand on the pyridinyl and N‐aryl units, the same group also reported highly enantioselective borylations of the α‐C−H bonds in five‐ to nine‐membered azacycles [41c] …”

Asymmetric C(sp3)–H borylation: an update

“…29 Of the optically active cyclobutane derivatives, enantioenriched cyclobutylboronates are the most versatile and appealing candidates. In 2020, Xu and his team 30 demonstrated the applicability of their previously developed chiral bidentate boryl ligand by incorporating cyclobutane carboxamides as a substrate. Surprisingly, their previous protocol was totally unsuccessful with respect to this transformation.…”