Communications
Asymmetric Catalysis
Consecutive Intermolecular Reductive Amination/Asymmetric
Hydrogenation: Facile Access to Sterically Tunable Chiral Vicinal
Diamines and N-Heterocyclic Carbenes
Abstract: A highly enantioselective iridium- or ruthenium-
catalyzed intermolecular reductive amination/asymmetric
hydrogenation relay with 2-quinoline aldehydes and aromatic
amines has been developed. A broad range of sterically tunable
chiral N,N’-diaryl vicinal diamines were obtained in high yields
(up to 95%) with excellent enantioselectivity (up to > 99% ee).
The resulting chiral diamines could be readily transformed into
sterically hindered chiral N-heterocyclic carbene (NHC)
precursors, which are otherwise difficult to access. The useful-
ness of this synthetic approach was further demonstrated by the
successful application of one of the chiral vicinal diamines and
chiral NHC ligands in a transition-metal-catalyzed asymmetric
Suzuki–Miyaura cross-coupling reaction and asymmetric ring-
opening cross-metathesis, respectively.
Figure 1. Selected examples of chiral 1,2-diamine-based biologically
active compounds and chiral ligands and catalysts. Cy=cyclohexyl,
Ts =p-toluenesulfonyl.
C
hiral vicinal diamines are important structural moieties
N-Heterocyclic carbenes (NHCs) have emerged as
a unique class of ligands and organocatalysts for a huge
number of catalytic transformations over the last two
decades.[1g,8] Among them, imidazolium-derived NHCs, such
as 1,3-bis(2,4,6-trimethylphenyl)imidazol-2-ylidene (IMes),[9]
have been widely used for transition-metal catalysis. How-
ever, only a few chiral variants of IMes have been reported so
far.[10] Such chiral NHCs could be readily accessed through
the direct derivatization of vicinal diamines.[10a–f] However, to
the best of our knowledge, the direct catalytic asymmetric
synthesis of sterically hindered N,N’-diaryl vicinal diamines
has not been achieved.[11,12]
Asymmetric hydrogenation has proven to be one of the
most powerful methods for the preparation of various chiral
amines.[13] However, examples of the direct synthesis of chiral
vicinal diamines by catalytic asymmetric hydrogenation are
extremely rare.[12,14] Previously, we demonstrated that the
cationic ruthenium or iridium complexes of chiral mono-
sulfonated diamines[1e] are excellent catalysts in the asym-
metric hydrogenation of quinoline derivatives and keti-
mines.[15] Later, this catalytic system was successfully applied
to the asymmetric hydrogenation of 2,2’-bisquinoline deriv-
atives, affording direct access to chiral endocyclic vicinal
diamines.[12] However, this method suffered from difficulties
in substrate synthesis and low stereoselectivity for sterically
hindered substrates. More recently, an asymmetric tandem
reaction of quinolinyl- and quinoxalinyl-containing ketones
was realized with this catalytic system, providing access to
chiral benzo-fused N-heterocyclic compounds.[16] Encouraged
by these results, we envisioned that readily available 2-
quinoline aldehydes and aromatic amines could be utilized to
prepare chiral N,N’-diaryl vicinal diamines through a relay
sequence of intermolecular reductive amination and asym-
metric hydrogenation of quinolines (Scheme 1). In this
found in a variety of biologically active natural products and
pharmaceuticals (A1–A4, Figure 1), as well as in chiral
ligands and catalysts for transition-metal-catalyzed asymmet-
ric reactions and organocatalysis (A5–A8, Figure 1).[1]
Accordingly, the development of efficient synthetic routes
to chiral vicinal diamines has attracted great interest over the
past decades. To date, a number of elegant synthetic methods
based on asymmetric catalysis have been reported.[2–7] How-
ever, most of these methods still suffer from narrow substrate
scope, the requirement of electron-withdrawing protecting
groups and subsequent transformation to form the free
amines, and/or the inability to differentiate the two amino
groups in the product. Therefore, it is highly desirable to
develop direct and atom-economical approaches to the
catalytic asymmetric synthesis of unprotected chiral vicinal
diamines with structural diversity from simple starting
materials.
[*] Y. Chen, Y. Pan, Y.-M. He, Prof. Dr. Q.-H. Fan
Beijing National Laboratory for Molecular Sciences
CAS Key Laboratory of Molecular Recognition and Function
Institute of Chemistry, Chinese Academy of Sciences (ICCAS)
University of Chinese Academy of Sciences
Beijing 100190 (P. R. China)
E-mail: heym@iccas.ac.cn
Prof. Dr. Q.-H. Fan
Collaborative Innovation Center of Chemical Science and
Engineering
Tianjin 300072 (P. R. China)
Supporting information and the ORCID identification number(s) for
the author(s) of this article can be found under:
Angew. Chem. Int. Ed. 2019, 58, 1 – 5
ꢀ 2019 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
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