substrate. A three-dimensional (3D) repre-
sentation of the transition state leading to
the major enantiomer, which was optimized
without artificial force at the GFN2-xTB level
of theory and further refined by the M06-L
density functional including D3 empirical
dispersion correction (SDD for Ir, 6-31G),
is shown in Fig. 4A. The space-filling repre-
sentation is given in Fig. 4B. An accessible
surfaceisformedasadeepcavitycreatedby
the modular catalyst that presents the urea
hydrogen-bonding site at the outer rim with
the Ir atom at the bottom of the groove. One
of the naphthalene rings ofLhasp/pinter-
actions not only with the pyridine moiety
but also with theortho-phenylene linker of
RL, forming a well-defined multicomponent
catalyst assembly (see fig. S12 for a plot of
noncovalent interactions and movies S1 and
S2 for overall views of the calculated transi-
tion state).
The amide substrate, which adopts a nor-
mal extended conformation, is bound in the
cavity not only through hydrogen bonding
with the urea moiety, but also through other
noncovalent interactions with the inner sur-
face of the cavity (Fig. 4). The urea donates
two N–H bonds to the amide carbonyl group,
resulting in bidentate hydrogen bonding. The
noncovalent interactions donated by the cat-
alyst surface include two C(sp^3 )–H···O inter-
actions ( 19 , 29 ): one between theb-C–Hbond
and O^1 of the phosphite ligandL*,andthe
other between the C–Hbondoftheterminal
Me group and O^4 of the B^1 pin ligand. In ad-
dition, London dispersion interactions seem
to contribute to the substrate binding in the
catalytic cavity. The 3D representations high-
light that whereas the pro-R-g-C–Hbondof
the substrate is activated by the Ir atom, the
terminal methyl substituent at the stereogenic
center is situated at the topmost vicinity of the
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ACKNOWLEDGMENTS
Funding:This work was supported by JSPS KAKENHI grant no.
JP15H05801 in Precisely Designed Catalysts with Customized
Scaffolding and JSPS KAKENHI grant no. JP18H03906 in Grant-in-
Aid for Scientific Research (A) to M. Sawamura, by JSPS KAKENHI
grant no. 20K15269 in Grant-in-Aid for Early Career Scientists
to R.L.R., and by the Uehara Memorial Foundation to T.I.Author
contributions:M. Sawamura, T.I., and R.L.R. conceived and
designed the experiments. R.L.R. and M. Sato performed the
experiments along with the preparation of the supplementary
materials. K.S. and S.M. performed the quantum chemical
calculations. M. Sawamura supervised the entire project. All
authors discussed the results and helped in writing the manuscript.
Competing interests:M.S., R.L.R., T.I., and S.M. are inventors
of patent application JP, 2020-133238 submitted by Hokkaido
University that covers urea-pyridine–type monodentate ligands,
borylation catalysts, and methods for preparation of organoboron
compounds using the catalysts. The authors declare no other
competing interests.Data and materials availability:
Characterization data for all compounds in this study, along
with details of the calculations and optimization of transition
states, are available in the supplementary materials.SUPPLEMENTARY MATERIALS
science.sciencemag.org/content/369/6506/970/suppl/DC1
Materials and Methods
Figs. S1 to S12
Tables S1 to S4
HPLC Data
NMR Spectra
Movies S1 and S2
References ( 30 – 70 )16 May 2020; accepted 29 June 2020
10.1126/science.abc8320Reyeset al.,Science 369 , 970–974 (2020) 21 August 2020 5of5
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