Shi Y,
Yang Y,
Xu S.
*
Lanzhou Institute of Chemical Physics, University of Chinese Academy of Sciences,
Beijing, and Hangzhou Normal University, P. R. of China
Iridium-Catalyzed Enantioselective C(sp
3)–H Borylation of Aminocyclopropanes.
Angew. Chem. Int. Ed. 2022;
61: e202201463
DOI:
10.1002/anie.202201463
Key words
C–H bond activation - boronate esters - iridium catalysis - cyclopropylamines - succinimides
Significance
A judicious choice of both ligand and directing group (DG) plays an important role
in the reactivity, regioselectivity, and stereoselectivity of a C–H functionalization
reaction, with the cyclometalation typically dictating the observed regioselectivity.
Whereas five-membered metallacycles are common, examples of asymmetric C–H functionalizations
involving four- or six-membered rings are rare. The current report describes a method
for the C–H borylation of aminocyclopropanes 1 and the identification of a suitable DG for achieving selective C–H borylation while
avoiding competing
σ-bond hydroboration.
Comment
Several potential DGs were evaluated with the succinimide 3 leading to selective borylation of the vicinal C(sp3)–H bond under iridium-catalyzed conditions, albeit with only 9% ee. Optimization
of the ligand by increasing the steric bulk of the ortho substituent on the N-aryl ring led to significantly enhanced enantioselectivities, whereas tuning of the
pyridine C5 substituent permitted a range of both N-protecting groups (3–8) and
α-substituents (11–15) to be tolerated in the process. A gram-scale preparation and several synthetic applications
of the products are demonstrated through both manipulation of the DG and cross-coupling
of the BPin moiety.
