A Disulfonimide Catalyst for Highly Enantioselective Mukaiyama-Mannich Reaction

Article abstract of DOI:10.1021/acs.orglett.6b02262

A new BINOL-derived chiral disulfonimide has been developed by introducing 4-methyl-3,5-dinitrophenyl substituents at its 3- and 3′-positions. This chiral disulfonimide catalyst displays high catalytic efficacy toward the asymmetric Mukaiyama-Mannich reac

Full text of DOI:10.1021/acs.orglett.6b02262

Letter
pubs.acs.org/OrgLett
A Disulfonimide Catalyst for Highly Enantioselective Mukaiyama−
Mannich Reaction
Fengtao Zhou* and Hisashi Yamamoto*,†
,†,‡
†
Molecular Catalyst Research Center, Chubu University, 1200 Matsumoto-cho, Kasugai, Aichi 487-8501, Japan
‡
Department of Applied Chemistry, School of Science, Northwestern Polytechnical University, Xi’an 710072, China
*
S Supporting Information
ABSTRACT: A new BINOL-derived chiral disulfonimide has
been developed by introducing 4-methyl-3,5-dinitrophenyl
substituents at its 3- and 3′-positions. This chiral disulfonimide
catalyst displays high catalytic efficacy toward the asymmetric
Mukaiyama−Mannich reaction of imines with ketene silyl
acetals leading to β-amino acid esters in good yields (up to
9
9%) with high diastereoselectivities (syn/anti up to 97:3) and
enantioselectivities (up to 98% ee). The long-standing problem
of the chiral phosphoric acid-catalyzed asymmetric Mukaiyama−Mannich reaction that requires a 2-hydroxyphenyl moiety was
solved by this disulfonimide catalyst.
1
19c
great breakthrough reported by Akiyama’s group and
enantioselective sulfoxidation,
cyclization,
asymmetric Prins cyclization,
asymmetric carbonyl−ene
19e
2
19d
A
Terada’s group in 2004 demonstrated that chiral
asymmetric oxa-Pictet−Spengler reaction,
19f,g 19h
binaphthol-derived phosphoric acids are efficient and highly
enantioselective catalysts for addition reactions to imines.
During the past decade, the field of asymmetric Brønsted acid
catalysis has attracted great attention from the synthetic
chemical community. One of the significant tasks in that field
is the design and synthesis of new Brønsted acid catalyst
scaffolds to overcome certain limitations in this area, such as
and so on. The design of
new disulfonimide catalysts that have a sterically highly
demanding chiral microenvironment similar to List’s imidodi-
phosphoric acid catalysts was highly desirable to allow some
challenging substrates to proceed in an enantioselective fashion
(Scheme 1).
On the other hand, the key to the successful application of
chiral phosphoric acids in asymmetric catalysis is their
bifunctional nature. Because of the presence of both a Brønsted
acidic site and a Lewis basic site on phosphoric acid catalysts,
render themselves to have a possibility of the formation of dual
activation via hydrogen-bonding interactions with substrates
3
low reactivity and the limitation of the scope of substrates. For
4
example, in 2006 our group developed a more acidic N-triflyl
phosphoramide catalyst for asymmetric Diels−Alder reactions.
In 2008, a chiral BINOL-disulfonic acid was reported as a
strong chiral Brønsted acid for direct asymmetric Mannich-type
reaction by Ishihara’s group. In the same year, List’s group
reported a sulfonic acid as strong Brønsted acid for Hosomi−
Sakurai reactions. In 2009, List’s group and Giernoth’s group
reported a new type of chiral disulfonimide derived from a
binaphthyl skeleton. Chiral disulfonimide catalysts have
recently been recognized as powerful silicon-based Lewis acid
catalysts as well as chiral Brønsted acid catalysts for asymmetric
5
6
3
such as imines. For example, chiral phosphoric acid-catalyzed
Mukaiyama−Mannich reactions require a 2-hydroxyphenyl
moiety of the aldimine for the formation of the tight cyclic
transition state between the phosphoric acid and aldimine.
However, very simple imines containing no 2-hydroxyphenyl
moiety are very challenging substrates, and only moderate
enantioselectivity has been achieved (39% ee), as reported by
7
8
1
20
7
Akiyama (Scheme 2). Our group developed a Brønsted acid-
assisted chiral Brønsted (chiral BBA) acid catalyst for
asymmetric Mukaiyama−Mannich reactions with imines
containing no 2-hydroxyphenyl moiety, and moderate
enantioselectivity was achieved (69% ee). Recently, our group
Mukaiyama aldol reactions, vinylogous and bisvinylogous
9
10
11
variants, hetero-Diels−Alder reactions, methallylations,
12
Mukaiyama−Mannich reactions, vinylogous Mukaiyama−
13
14
Mannich reactions, asymmetric Torgov cyclization, Abra-
1
5
16
17,18
mov reactions, reduction reactions and so on.
However,
21
developed a powerful BINOL-derived chiral phosphoric acid
catalyst for highly enantioselective (up to >99% ee) and
diastereoselective (syn/anti up to >99:1) asymmetric Mukaiya-
ma−Mannich reactions. However, simple imines containing no
some simple substrates that do not have sterically demanding
groups or bulky substituents are still not suitable for
enantioselective transformations. This might be because current
catalysts cannot provide a very compact chiral microenviron-
ment to achieve a high level of enantioinduction. Recently,
List’s group developed a new class of imidodiphosphoric acid
catalysts with a confined active site that have proven to be
1
9
2
-hydroxyphenyl moiety are still not suitable substrates for this
Received: August 16, 2016
19a,b
highly efficient catalysts for asymmetric acetalization,
©
XXXX American Chemical Society
A
DOI: 10.1021/acs.orglett.6b02262
Org. Lett. XXXX, XXX, XXX−XXX

Organic Letters
Letter
Scheme 1. New Catalyst Design
Scheme 4. Scope of the Disulfonimide-Catalyzed
Enantioselective Mannich-Type Reaction
a
Scheme 2. Chiral Acid Catalysts for Mukaiyama−Mannich
Reactions
a
Reaction conditions: All reactions were performed at −78 °C for 24 h
under nitrogen with 1 (0.1 mmol, 1.0 equiv), 2 (0.3 mmol, 3.0 equiv),
and catalyst 4c (0.005 mmol, 5 mol %) in toluene (1 mL). Product ee
values were determined by HPLC on a chiral stationary phase.
Scheme 3. Optimization of the Mannich Reaction with
a
Various Chiral Catalysts
as List’s imidodiphosphoric acid catalysts in order to address
the limitation of chiral phosphoric acids that requires double
activations to achieve high enantioselectivity. We envisage that
such a chiral disulfonimide will enable imines containing no 2-
hydroxyphenyl moiety to proceed smoothly via single-site
interactions. Meanwhile, this chiral disulfonimide provides a
constrained chiral microenvironment and allows the simple
substrate to have a strong steric interaction with the catalyst to
achieve a high level of enantiocontrol. In this context, we
disclose an efficient chiral disulfonimide catalyst based on a
binaphthyl skeleton for symmetric Mukaiyama−Mannich
reactions, and the corresponding products were obtained in
good yields with excellent enantioselectivities (up to 98% ee)
and good diastereoselectivities (up to 97:3 syn/anti).
a
Reaction conditions: All reactions were performed at −78 °C for 24 h
We initially investigated the acid-catalyzed Mukaiyama−
Mannich reaction of imine 1a with ketene silyl acetals 2 and
tested catalysts 4a−d. The results are shown in Scheme 3. In
under nitrogen with 1 (0.1 mmol, 1.0 equiv), 2 (0.3 mmol, 3.0 equiv),
and catalyst 4 (0.005 mmol, 5 mol %) in toluene (1 mL), unless
otherwise noted. Product ee values were determined by HPLC on a
chiral stationary phase. Catalyst loading 2.5 mol %. Catalyst loading
1
20
b
c
our previous work, the N-triflyl phosphoramide catalyst 4a
was an efficient catalyst for this model reaction and gave good
enantioselectivity (96% yield, 94% ee). We turned to designing
a new class of disulfonimide catalysts to improve enantiose-
lectivity further. We envisaged that the introduction of a nitro
group serving as electron-withdrawing substituent on the
catalysts would enhance their acidity. To our delight, catalyst
4b bearing the 3,5-dinitro-4-methylphenyl group led to a
smooth Mukaiyama−Mannich reaction, giving 3a in excellent
d
.0 mol %. At −90 °C for 48 h.
catalyst; only moderate enantioselectivity was obtained (80%
ee). Inspired by the successful applications of chiral
disulfonimide catalysts and imidodiphosphoric acid catalysts
in asymmetric organocatalysis, we now have designed a new
type of chiral disulfonimide catalyst that has a similar active site
17
19
B
DOI: 10.1021/acs.orglett.6b02262
Org. Lett. XXXX, XXX, XXX−XXX

Organic Letters
Letter
Scheme 5. Scope of the Disulfonimide-Catalyzed
Diasteroselective and Enantioselective Mannich-Type
Reaction
anti up to 97:3) and excellent enantioselectivities (up to 95%
ee). The absolute configuration of the major isomer of 6e was
determined to be (2S,3R) by X-ray analysis.
a
22
In summary, we have successfully developed a powerful
BINOL-derived chiral disulfonimide catalyst bearing 4-methyl-
3
,5-dinitrophenyl substituents. The utility of this chiral
disulfonimide catalyst was demonstrated by an asymmetric
Mukaiyama−Mannich reaction of imines with ketene silyl
acetals to afford β-amino acid esters in good yields with
excellent diastereo- and enantioselectivities. In particular, this
disulfonimide catalyst overcomes the long-standing limitation
of the chiral phosphoric acid-catalyzed asymmetric Mukaiya-
ma−Mannich reaction, namely, the requirement of the 2-
hydroxyphenyl moiety. Further exploration of the application of
this disulfonimide catalyst is underway in our laboratory.
ASSOCIATED CONTENT
Supporting Information
■
*
S
The Supporting Information is available free of charge on the
ACS Publications website at DOI: 10.1021/acs.or-
glett.6b02262.
Experimental details, characterization data for all
a
Reaction conditions: All reactions were performed at −78 °C for 24 h
1
13
compounds, and copies of HPLC data and H and
C
under nitrogen with 1 (0.1 mmol, 1.0 equiv), 5 (0.3 mmol, 3.0 equiv),
and catalyst 4c (0.005 mmol, 5 mol %) in toluene (1 mL). Product ee
values were determined by HPLC on a chiral stationary phase. The
NMR spectra (PDF)
Crystallographic data for 6e (CIF)
Crystallographic data for 6e (CIF)
1
diastereoselectivity ratios were determined by H NMR analysis.
yield with moderate enantioselectivity (97% yield, 77% ee).
Furthermore, catalyst 4c bearing a methoxy group resulted in a
higher enantioselectivity (95% yield, 96% ee) compared with
catalyst 4a. Catalyst 4d bearing a benzyl group gave the
corresponding product in good yields but with a slightly lower
enantioselectivity (93% ee). Next, the catalyst loading and
reaction temperature were investigated. It is noteworthy that
the enantioselectivity dropped sharply when the catalyst
loading was decreased to 1.0 mol %. A slightly lower
enantioselectivity (89% ee) was observed at lower temperature
AUTHOR INFORMATION
Corresponding Authors
■
*
*
E-mail: hyamamoto@isc.chubu.ac.jp.
E-mail: fengtaozhou@nwpu.edu.cn.
Notes
The authors declare no competing financial interest.
ACKNOWLEDGMENTS
■
This work was supported by ACT-C, JST. The authors thank
Dr. Y. Shimoda in our lab at Chubu University for his helpful
discussions.
(
−90 °C).
With the optimized reaction conditions in hand, the scope of
the disulfonimide 4c-catalyzed Mukaiyama−Mannich reaction
was explored, and the results are shown in Scheme 4. Aldimines
derived from aromatic aldehydes bearing either an electron-
withdrawing group (e.g., Br, Cl) or an electron-donating group
DEDICATION
■
This work is dedicated to Professor Dieter Enders on the
occasion of his 70th birthday.
(
e.g., OMe, Me) work very well, furnishing the corresponding
products 3a−g in good yields with excellent enantioselectivities
up to 98% ee). Furthermore, reactions with aldimines derived
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D
DOI: 10.1021/acs.orglett.6b02262
Org. Lett. XXXX, XXX, XXX−XXX