Journal of the American Chemical Society
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9:1 dr and 98% ee.
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To demonstrate the stereodivergence of this allylation
reaction further, the diastereomers of 3ca, 3da, 3ka, 3ag,
3ai and 3al were prepared by conducting the reactions
with the corresponding azaaryl nucleophiles and the car-
bonates in the presence of ent-[Ir] instead of [Ir] under
otherwise identical conditions (Table 4). The correspond-
ing products (4ca, 4da, 4ka, 4ag, 4ai, 4al) were obtained
from these reactions in yields, diastereo- and enantioselec-
tivity that are comparable to those of the reactions that
form their diastereomers.
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In summary, we have developed a combination of cata-
lysts that enable stereodivergent allylic substitution reac-
tions with azaaryl acetamides and acetates. This combina-
tion of catalysts comprises a chiral metallacyclic iridium
complex and a chiral bisphosphine-ligated copper(I) com-
plex. The phosphoramidite binds Ir tightly through a stable
Ir–C bond, which prevents potential crossover of two lig-
ands on two metal centers. The copper(I) complex acts as a
Lewis acid to activate the azaaryl carboxylic acid deriva-
tives by coordinating to the imine moieties (C=N) embed-
ded in the azaaryl rings and the suitably positioned car-
bonyl groups, and this binding mode of the chiral complex
controls the geometry and facial selectivity of the Cu(I)
enolates in the allylation reactions. Azaaryl substrates that
bear pyridyl, benzoxazolyl, benzothiazolyl, pyrazinyl,
quinolinyl and isoquinolinyl moieties all underwent this
reaction, delivering the products containing two adjacent
tertiary stereocenters in high yields with excellent dia-
stereo- and enantioselectivity. Starting from the same set
of substrates, simple variation of the enantiomers of the
two catalysts allow the synthesis of all four possible ste-
reoisomers of the products individually. Studies to under-
stand the origin of stereoselectivity of the Cu(I) enolates in
the allylation reactions are ongoing in our laboratories.
ASSOCIATED CONTENT
Supporting Information.
The Supporting Information is available free of charge on
the ACS Publications website.
Experimental procedures and spectra (PDF)
Crystallographic data for 3ca (CIF)
Crystallographic data for 4ca (CIF)
AUTHOR INFORMATION
Corresponding Author
*jhartwig@berkeley.edu
ORCID
John F. Hartwig: 0000-0002-4157-468X
Corresponding Author
The authors declare no competing financial interest.
ACKNOWLEDGMENT
We thank the NIH-NIGMS (GM-55382) for financial sup-
port and Xiaokun Pei for assistance with X-ray crystallo-
graphic analysis. P.B. thanks the German National Academ-
ic Foundation (Studienstiftung) for support.
(7) For selected recent publications: (a) Kumagai, N.; Kanai, M.;
Sasai, H. ACS Catal. 2016, 6, 4699; (b) Liu, Z.; Takeuchi, T.; Pluta,
R.; Arteaga, F.; Kumagai, N.; Shibasaki, M. Org. Lett. 2017, 19, 710;
(c) Sun, B.; Balaji, P. V.; Kumagai, N.; Shibasaki, M. J. Am. Chem. Soc.
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