(fig. S2). Alkylarenes bearing a bulky substit-
uent such astert-butyl (1a) or adamantyl (1b)
reacted with highmetaselectivity (23:1 and
29:1, respectively). A smaller secondary alkyl
group such as isopropyl (1c) or cyclohexyl (1d)
also gave high selectivity (15:1 and 14:1, re-
spectively), whereas substrates bearing small
groups such as ethyl (1e)andmethyl(1f) reacted
with moderatemetaselectivity (7.3:1 and 5.0:1,
respectively). For these substrates, steric con-
trol is strongly indicated because of (i) the lack
of functionality that might electronically inter-
act with the catalyst and (ii) the direct cor-
relation between the substrate size and selectivity
(see also the mechanistic discussion, Fig. 4).
The merits of remote regiocontrol, which does
not lower the activity of the catalyst, are illustrated
by the reaction of sterically demanding 1,3-di-
tert-butylbenzene (1g), which was unreactive
under steric control using bulky ligands ( 13 )
but could be borylated in moderate yield using
our catalyst.
Anilines, compounds of paramount impor-
tance for the chemical industry, can also be
borylated with highmetaselectivity, and the
selectivity was correlated with the size of the
N-substituents. Thus,N,N-disubstituted ani-
lines bearing bulky groups such as isopropyl
(1h), cyclohexyl (1i), or isobutyl (1j) gave the
meta-borylated products with selectivity higher
than 20:1, reaching as high as 45:1 for1j.N,N-
Dibutylaniline (1k) also reacted with high se-
lectivity (18:1). The reaction of less sterically
congested anilines such asN-phenylpyrrolidine
(1l) andN,N-dimethylaniline (1m) proceeded
with moderate selectivity (13:1 and 11:1, respec-tively). A diarylamine protected with a silyl
group (1n) reacted with high yield and high
metaselectivity (36:1), and selectively at the
less hindered phenyl ring. Electron-rich arenes
such as anilines are typically less reactive under
iridium-catalyzed borylation conditions ( 28 ),
but our roof ligand enabled the reaction of a
stoichiometric amount of these substrates in
good yields. For comparison, using dtbpy as
the ligand under otherwise identical condi-
tions,1kreacted in 5% yield.
Other monosubstituted arenes also reacted
withmetaselectivity. A phenol protected with
an easily removable triisopropylsilyl group (1o)
reacted with high yield and selectivity (21:1),
enabling straightforward access to synthetically
challengingmeta-substituted phenols ( 32 ) (see
also fig. S2). Isopropyl phenyl ether (1p) reactedSCIENCEscience.org 11 FEBRUARY 2022¥VOL 375 ISSUE 6581 659
Fig. 1. Steric control for undirected regioselec-
tive CÐH activation.(A) Strategies for
sterically induced regiocontrol. M, transition metal;
L, ligand. (B) The design of a“steric roof”
ligand for remote regiocontrol. pin, pinacolate.
(C)Meta-selective borylation oftert-butylbenzene
and triisopropyl(phenoxy)silane. R, organic
group; cod, 1,5-cyclooctadiene; dtbpy,
4,4′-di-tert-butyl-2,2′-bipyridine; Me, methyl;
tBu,tert-butyl;iPr, isopropyl.RESEARCH | REPORTS