groups.) Enzyme inhibitor1rg( 30 ) could be
reduced in quantitative yield and 93:7 e.r.,
illustrating the applicability of the method
for late-stage derivatization. Existing stereo-
genic centers adjacent to the C=N bond ex-
hibit a strong substrate control. For instance,
(R)-1rlpossessing ab-methyl stereogenic cen-
ter yielded cis-isomer (R,R)-2rlin 97:3 d.r. and
93:7 e.r. In contrast,b-ester analog (±)-1rm
gave trans-isomer2rmin 98:2 d.r., likely by
cis-hydrogenation followed by acid-promoted
epimerization of the ester to the thermodynam-
ically more stable product.N-methoxy deriva-
tives of norephedrine2sand estrone2twere
formed in highly diastereoselective fashion, the
former after double hydrogenation of1s.Fi-
nally, a 25-g batch ofE/Z-1rbwas hydrogenated
with a reduced 0.05 mol % catalyst loading
to (R)-2rbin a quantitative manner (turnover
number 4000) in 93:7 e.r., supporting the
scalability of the method. Overall, our find-
ings serve as a blueprint for further asymmetric
transition metal–catalyzed ionic hydrogena-
tions of challenging substrates, and highlight
the yet untapped potential of cyclometalated
chiral Cpxmetal complexes in catalysis.
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ACKNOWLEDGMENTS
We thank R. Scopelliti and F. Fadaei Tirani for x-ray
crystallographic analysis of compoundsIr3b-Iand (S)-2a-H+,
C. J. Cope and S. Masala for technical support, and V. Grushin
and A. Robinson for insightful discussions.Funding:Supported
by Syngenta Crop Protection AG and EPFL.Author
contributions:T.S. conceived the project. N.C. conceived
and supervised the project. J.M.-R. performed the experimental
work. All authors designed the experiments, analyzed the
data, and drafted the manuscript.Competing interests:The
authors have filed a patent application (GB 1818117.2) for
the described iridium-catalyzed asymmetric ionic oxime
hydrogenation.Data and materials availability:
Crystallographic data for compoundsIr3b-Iand (S)-2a-H+
areavailablefreeofchargefromCambridgeCrystallographic
Data Centre under reference numbers CCDC 1973002 and
1973003, respectively. All other characterization data and
detailed experimental procedures are available in the
supplementary materials.
SUPPLEMENTARY MATERIALS
science.sciencemag.org/content/368/6495/1098/suppl/DC1
Materials and Methods
Figs. S1 to S6
HPLC Traces
NMR Spectra
References ( 31 – 54 )
11 February 2020; accepted 17 April 2020
10.1126/science.abb2559
Mas-Rosellóet al.,Science 368 , 1098–1102 (2020) 5 June 2020 5of5
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