Anti-Selective Asymmetric Henry Reaction Catalyzed by a Heterobimetallic Cu-Sm-Aminophenol Sulfonamide Complex

Article abstract of DOI:10.1021/acs.orglett.6b00432

A novel heterobimetallic Cu/Sm/aminophenol sulfonamide complex has been developed by a convenient one-pot method for the anti-selective asymmetric Henry reaction. The corresponding anti-β-nitro alcohols are obtained in up to 99% yield, >30:1 dr, and 98% ee. The results of control experiments and ESI-MS analysis of the complex indicate that the monomeric bimetallic Cu/Sm/1 complex would be the active species.

Full text of DOI:10.1021/acs.orglett.6b00432

Letter
pubs.acs.org/OrgLett
anti-Selective Asymmetric Henry Reaction Catalyzed by a
Heterobimetallic Cu−Sm−Aminophenol Sulfonamide Complex
†
†
†
‡
,†
Yang Li, Ping Deng, Youmao Zeng, Yan Xiong, and Hui Zhou*
†School of Pharmaceutical Science, Chongqing Research Center for Pharmaceutical Engineering, Chongqing Key Laboratory of
Biochemistry and Molecular Pharmacology, Chongqing Medical University, Chongqing 400016, China
‡School of Chemistry and Chemical Engineering, Chongqing University, Chongqing 400030, China
*
S Supporting Information
ABSTRACT: A novel heterobimetallic Cu/Sm/aminophenol sulfonamide complex has been developed by a convenient one-pot
method for the anti-selective asymmetric Henry reaction. The corresponding anti-β-nitro alcohols are obtained in up to 99%
yield, >30:1 dr, and 98% ee. The results of control experiments and ESI-MS analysis of the complex indicate that the monomeric
bimetallic Cu/Sm/1 complex would be the active species.
ptically active β-nitro alcohols are key intermediates
The initial results of metal screening are summarized in Table 1.
O
and building blocks for the synthesis of bioactive natural
The combination of Cu(OAc) and Sm(O-iPr) with 1 afforded
2
3
1
products and pharmaceutical agents. The catalytic asymmetric
Henry reaction is a useful, atom-economical, step-economical,
carbon−carbon bond-forming reaction that affords enantiomeri-
the corresponding product 4aa in 90% yield with 14:1 anti/syn
and 93% ee (entry 1, Table 1). Neither Cu(OAc) nor Sm(O-iPr)
2
3
alone gave good results (entries 2−5, Table 1).
The 1:1:1 ratio of Cu(OAc) /Sm(O-iPr) /1 was also critical
for good selectivity (entry 1 vs entries 6 and 7, Table 1). In the
current catalytic system, Cu(OAc) and Sm(O-iPr) , as well as
2
cally enriched β-nitro alcohols. Since the pioneering application
2
3
3
,4
of Shibasaki’s heterometallic catalyst in the Henry reaction,
increasing efforts have been directed toward developing novel
catalytic systems. A series of metal complexes, especially
dinuclear metal complexes (such as Shibasaki’s heterobimetallic
2
3
the 1:1:1 ratio of Cu/Sm/1, were essential for good reactivity and
selectivity.
4
g,h
6c,d
6e,m−o
Cu/Sm,
Pd/La,
and Nd/Na
complexes, Trost’s
To gain some insight into the complex, ESI-MS (electrospray
4l,o
7
dinuclear Zn complex, Hong’s self-assembled dinuclear Co
ionization mass spectroscopy) studies were carried out. The
5
m
5n
complex, and Savoia’s dinuclear Cu complex for Henry reac-
tion or related aza-Henry reaction), as well as organocatalysts5,
were developed for the catalytic asymmetric Henry reaction.
However, diastereo- and enantioselective Henry reactions
between aldehydes and nitroethane or other nitroalkanes are
spectrum of the 1:1:1 Cu/Sm/1 mixture with the additive
iPr NEt displayed ions at m/z 1131.43 and 1279.42, which
2
corresponded to Cu /1 and Cu/Sm/1. As the corresponding
2
complexes between Cu(OAc) and 1 could not catalyze this
2
reaction even in the presence of 30 mol % of iPr NEt (entries 2
2
6
and 3, Table 1), we speculated that the 1:1:1 Cu/Sm/1 complex
more challenging for low reactivity and poor selectivity. Although
8
,9
(
Scheme 1) would be the active species.
great progress has been achieved, developing new catalysts for the
diastereoselective and enantioselective Henry reaction of
aldehydes with nitroethane is still necessary. Herein, we report a
novel heterobimetallic Cu/Sm/1 complex (Scheme 1) generated
in one pot for the anti-selective Henry reaction.
It is worth mentioning that the addition order of Cu(OAc)2
and Sm(O-iPr) could hardly affect the ee values of the anti-
3
product (entries 1, 8, and 9, Table 1), whereas an inferior yield
and dr were observed when reversing the addition order of
Cu(OAc) and Sm(O-iPr) (entry 9 vs entries 1 and 8, Table 1).
We recently reported an asymmetric Henry reaction with
nitromethane as a donor promoted by a dinuclear nickel com-
2
3
We speculated that the resulting active species by the stepwise
method and the one-pot method were the same. So we chose the
5
o
plex. This catalytic system was not suitable for nitroethane or
other nitroalkanes. Therefore, a series of aminophenol sulfo-
namide ligands derived from chiral diamine were screened for
this conversion, and we found that 1 was a promising candidate.
Received: February 14, 2016
©
XXXX American Chemical Society
A
DOI: 10.1021/acs.orglett.6b00432
Org. Lett. XXXX, XXX, XXX−XXX

Organic Letters
Letter
Scheme 1. Aminophenol Sulfonamide Ligand 1 and the Proposed Structure of the Heterobimetallic Cu/Sm/1 Complex
Table 1. Screening of Metal Saltsa,b
c
d
e
entry
M1
M2
yield (%)
90
anti/syn
ee (%) (anti)
1
2
3
4
5
6
7
Cu(OAc) (10 mol %)
Sm(O-iPr) (10 mol %)
14:1
93
2
3
f
Cu(OAc) (10 mol %)
none
none
none
none
nr
2
f
Cu(OAc) (20 mol %)
nr
2
Sm(O-iPr) (10 mol %)
23
89
90
56
90
80
2:1
2:1
0
0
3
Sm(O-iPr) (20 mol %)
3
Cu(OAc) (10 mol %)
Sm(O-iPr) (20 mol %)
6:1
87
91
93
94
2
3
Cu(OAc) (20 mol %)
Sm(O-iPr) (10 mol %)
11:1
14:1
11:1
2
3
g
8
Cu(OAc) (10 mol %)
Sm(O-iPr) (10 mol %)
2
3
9
Sm(O-iPr) (10 mol %)
Cu(OAc) (10 mol %)
3
2
a
Reactions were carried out on a 0.2 mmol scale (benzaldehyde) with nitroethane (0.2 mL) in THF (0.9 mL) in the presence of 1 (10 mol %), M1
b
(
3
x mol %), and M2 (y mol %) at −30 °C for 90 h. Unless otherwise noted, the catalyst was prepared as follows: 1 and M1 were stirred in THF at
5 °C for 1 h to generate the precatalyst; M2 was added to the precatalyst in THF, and stirring was continued for another 1 h to generate the
c
d
e
catalyst. For details, see Supporting Information. Isolated yield. Determined by chiral HPLC analysis (Chiralpak AD-H). Determined by chiral
HPLC analysis (Chiralpak AD-H) for the anti-product. No reaction. 1, M1, and M2 were added in one pot.
f
g
a
Table 2. anti-Selective Henry Reactions with Various Aldehydes and Nitroalkanes
b
c
d
entry
R
2
R′
CH3
3
product
time (h)
yield (%)
anti/syn
ee (%)
1
2
3
4
5
6
7
8
9
Ph
2-NO C H
4
2a
2b
2c
2d
2e
2f
3a
3a
3a
3a
3a
3a
3a
3a
3a
3a
3a
3a
3a
3a
3a
3b
4aa
4ba
4ca
4da
4ea
4fa
90
121
87
90
99
99
99
68
98
77
96
99
97
68
93
99
78
54
56
14:1
>30:1
11:1
14:1
16:1
24:1
12:1
20:1
24:1
>30:1
11:1
24:1
14:1
16:1
3:1
93
96
92
92
89
96
94
94
94
98
92
88
92
95
85
86
CH3
CH3
CH3
CH3
CH3
CH3
CH3
CH3
CH3
CH3
CH3
CH3
CH3
CH3
2
6
4-F CC H
4
3
6
4-FC H
140
115
115
115
162
116
112
162
162
162
162
168
168
6
4
2-MeC H
6
4
3-MeC H
6
4
4
4-MeC H
2g
2h
2i
4ga
4ha
4ia
6
2-furyl
5-Br-2-furyl
PhCHCH
4-MeOC H
1
0
2j
4ja
e
1
1
2
3
4
2k
2l
4ka
4la
6
4
e
e
e
f
1
1
1
1
1-naphthyl
2-naphthyl
2-thienyl
n-hexyl
Ph
2m
2n
2o
2a
4ma
4na
4oa
4ab
5
e
16
CH CH
20:1
3
2
a
Unless otherwise noted, all reactions were carried out on a 0.2 mmol scale of aldehyde with nitroalkane (0.2 mL) in THF (0.9 mL) in the presence
b
c
1
of 10 mol % of Cu/Sm/1 generated in one pot and 30 mol % of iPr NEt at −30 °C. Isolated yield. Determined by H NMR spectroscopy analysis.
2
d
e
f
Determined by chiral HPLC analysis for the anti-product. 40 mol % of iPr NEt was used. 50 mol % of iPr NEt was used.
2
2
B
DOI: 10.1021/acs.orglett.6b00432
Org. Lett. XXXX, XXX, XXX−XXX

Organic Letters
Letter
one-pot method to prepare the heterometallic catalyst, which
would greatly facilitate the operation.
(3) (a) Sasai, H.; Suzuki, T.; Arai, S.; Arai, T.; Shibasaki, M. J. Am.
Chem. Soc. 1992, 114, 4418−4420. (b) Sasai, H.; Tokunaga, T.;
Watanabe, S.; Suzuki, T.; Itoh, N.; Shibasaki, M. J. Org. Chem. 1995, 60,
Next, the substrate scope of the reaction was evaluated, and the
results are summarized in Table 2. Aryl aldehydes with either an
electron-donating substituent or an electron-withdrawing
substituent, as well as heteroaryl aldehydes, afforded the products
in high yield, anti-selectivity, and ee (entries 2−9, Table 2).
The α,β-unsaturated aldehyde 2j gave product 4ja with excel-
lent yield, dr, and ee (entry 10, Table 2). For the less reactive
7
(
388−7389.
4) For selected literature on multimetallic catalysts, see: (a) Shibasaki,
M.; Sasai, H.; Arai, T. Angew. Chem., Int. Ed. Engl. 1997, 36, 1236−1256.
(b) Shibasaki, M.; Yoshikawa, N. Chem. Rev. 2002, 102, 2187−2210.
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(d) Shibasaki, M.; Kanai, M.; Matsunaga, S.; Kumagai, N. Acc. Chem. Res.
2
009, 42, 1117−1127. (e) Matsunaga, S.; Shibasaki, M. Synthesis 2013,
aldehydes 2k−o, more iPr NEt was required for good conversion
45, 421−437. (f) Matsunaga, S.; Shibasaki, M. Chem. Commun. 2014, 50,
1044−1057. (g) Handa, S.; Gnanadesikan, V.; Matsunaga, S.; Shibasaki,
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2
(
entries 11−15, Table 2). The aliphatic aldehyde 2o afforded
product 2oa in high ee, albeit with moderate yield and anti-
selectivity (entry 15, Table 2). Besides, 1-nitropropane was also
employed as the nucleophile to react with benzaldehyde. The
corresponding product 4ab was obtained with 20:1 anti/syn and
2
2
1
2
010, 132, 4925−4934. (i) Trost, B. M.; Bartlett, M. J. Acc. Chem. Res.
015, 48, 688−701. (j) Trost, B. M.; Ito, H. J. Am. Chem. Soc. 2000, 122,
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001, 123, 3367−3368. (l) Trost, B. M.; Yeh, V. S. C. Angew. Chem., Int.
8
6% ee (entry 16, Table 2).
In summary, a highly efficient anti-selective catalytic asym-
Ed. 2002, 41, 861−863. (m) Trost, B. M.; Weiss, A. H.; Von Wangelin,
A. J. J. Am. Chem. Soc. 2006, 128, 8−9. (n) Trost, B. M.;
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metric Henry reaction has been developed by using a novel
heterometallic Cu/Sm/1 complex generated in one pot. Various
anti-β-nitro alcohols were obtained in moderate to excellent
yields with high to excellent enantioselectivities and moderate to
excellent diastereoselectivities. Further investigations are under-
2
778−2779. (o) Trost, B. M.; Lupton, D. W. Org. Lett. 2007, 9, 2023−
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refs therein.
10
way in our laboratory for the detailed mechanism and the
application of the desired catalyst to other reactions.
(5) For selected examples of the catalytic asymmetric Henry reaction
between nitromethane and carbonyl compounds, see: (a) Corey, E. J.;
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ASSOCIATED CONTENT
Supporting Information
■
*
S
The Supporting Information is available free of charge on the
ACS Publications website at DOI: 10.1021/acs.orglett.6b00432.
2
222−2223. (d) Evans, D. A.; Seidel, D.; Rueping, M.; Lam, H. W.;
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procedure, and NMR, MS, and HPLC spectra (PDF)
(
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AUTHOR INFORMATION
Corresponding Author
■
*
E-mail: hzhou@cqmu.edu.cn.
Notes
The authors declare no competing financial interest.
2
007, 72, 9323−9328. (k) Ma, K. Y.; You, J. S. Chem. - Eur. J. 2007, 13,
1
863−1871. (l) Bandini, M.; Piccinelli, F.; Tommasi, S.; Umani-Ronchi,
ACKNOWLEDGMENTS
A.; Ventrici, C. Chem. Commun. 2007, 616−618. (m) Park, J.; Lang, K.;
Abboud, K. A.; Hong, S. J. Am. Chem. Soc. 2008, 130, 16484−16485.
■
We are grateful for the generous financial support by the National
Natural Science Foundation of China (20902114, 21372265),
Fundamental and Advanced Research Projects of Chongqing
City (No. cstc2013jcyjA10144), and Scientific and Technological
Research Program of Chongqing Municipal Education Commis-
sion (KJ120307 and KJ1500221).
(n) Gualandi, A.; Cerisoli, L.; Stoeckli-Evans, H.; Savoia, D. J. Org. Chem.
2
011, 76, 3399−3408. (o) Liu, Y.; Deng, P.; Li, X.; Xiong, Y.; Zhou, H.
Synlett 2014, 25, 1735−1738. (p) Tanaka, K.; Iwashita, T.; Yoshida, E.;
Ishikawa, T.; Otuka, S.; Urbanczyk-Lipkowska, Z.; Takahashi, H. Chem.
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(
D
DOI: 10.1021/acs.orglett.6b00432
Org. Lett. XXXX, XXX, XXX−XXX