Practical asymmetric henry reaction catalyzed by a chiral diamine-Cu(OAc)2 complex

Article abstract of DOI:10.1021/ol7014362

The chiral diamine ligand 3 was designed and synthesized from (R,R)-1,2-diphenylethylenediamine, (S)-2,2′-dibromomethyl-1,1′- binaphthalene, and o-xylylene dibromide. The resulting 3-Cu(OAc)₂ complex was a highly efficient catalyst for the Henr

Full text of DOI:10.1021/ol7014362

ORGANIC
LETTERS
2007
Vol. 9, No. 18
3595-3597
Practical Asymmetric Henry Reaction
Catalyzed by a Chiral Diamine-Cu(OAc)2
Complex
Takayoshi Arai,* Masahiko Watanabe, and Akira Yanagisawa
Department of Chemistry, Graduate School of Science, Chiba UniVersity,
Inage 263-8522, Japan
tarai@faculty.chiba-u.jp
Received June 19, 2007
ABSTRACT
The chiral diamine ligand 3 was designed and synthesized from (R,R)-1,2-diphenylethylenediamine, (S)-2,2′-dibromomethyl-1,1′-binaphthalene,
and o-xylylene dibromide. The resulting 3-Cu(OAc)2 complex was a highly efficient catalyst for the Henry reaction, giving the various nitroaldols
with over 90% ee (up to >99%). The reaction was performed in n-propyl alcohol at room temperature, and the Henry adducts were produced
in high yield with excellent enantiomeric excess; these attributes are desirable in a catalyst for practical use.
The requirements for a useful chiral catalyst are that it must
provide only the target product, in high yield and excellent
enantiomeric excess, and must have broad general applica-
tion. If the catalyst is to be usefully applied in industry, it is
desirable that the reaction can be carried out without strict
temperature control or special care for air-sensitive reagents.1
From the point of view of protecting the environment, it is
particularly essential to minimize waste in synthetic pro-
cesses.2 These requirements must be taken into account when
researching and developing new chiral ligands.
have been used in various beneficial transformations to
provide chiral â-amino alcohols and R-hydroxy carboxylic
acids. To provide the raw materials for research into these
biologically significant building blocks, attention has recently
been focused on the development of catalytic, asymmetric
versions of the Henry reaction.3 The most impressive work
of heterobimetallic lanthanoid catalysis4a has stimulated the
successful development of various types of asymmetric
catalyst.4 Among them, the Cu-catalyzed Henry reaction
performed at room temperature has received much attention
in recent years.4b,d,j-m
The Henry (nitroaldol) reaction is one of the most atom-
economical carbon-carbon bond-forming reactions in syn-
thetic chemistry. The resulting â-hydroxy nitro compounds
(3) (a) Shibasaki, M.; Gro¨ger, H. In ComprehensiVe Asymmetric Ca-
talysis; Jacobsen, E. N., Pfaltz, A., Yamamoto, H., Eds.; Springer: Berlin,
Germany, 1999; Vol. III, pp 1075-1090. (b) Shibasaki, M.; Go¨ger, H.;
Kanai, M. In ComprehensiVe Asymmetric Catalysis, Supplement 1; Jacobsen,
E. N., Pfaltz, A., Yamamoto, H., Eds.; Springer: Heidelberg, Germany,
2004; pp 131-133. (c) Palomo, C.; Oiarbide, M.; Laso, A. Eur. J. Org.
Chem. 2007, 2561.
(1) Hawkins, J. M.; Watson, T. J. N. Angew. Chem., Int. Ed. 2004, 43,
3224.
(2) Anastas, R. T.; Warner, J. C. Green Chemistry, Theory and Practice;
Oxford University Press: Oxford, UK, 1998.
10.1021/ol7014362 CCC: $37.00
© 2007 American Chemical Society
Published on Web 08/04/2007

Figure 1. Designer chiral diamine 3.
We previously reported a facile enantioselective Henry
reaction catalyzed by a C2-symmetric diamine (1)-Cu(I)
catalyst.5 The reaction of o-nitrobenzaldehyde with ni-
tromethane was catalyzed by 1-CuCl to provide the corre-
sponding adduct in >99% yield with 90% ee (20 h, rt).
However, there are some practical difficulties associated with
the use of 1-CuCl as a catalyst, such as the presence of a
hygroscopic cyclohexyl-1,2-diamine structure in 1. The
second drawback of the previously developed catalyst is the
use of an air-sensitive Cu(I) salt. A Cu(II)-catalyzed Henry
reaction developed by Jørgensen and Evans has apparent
advantages for practical application.4b,d According to the
reaction mechanism proposed by Evans,4d the weakly Lewis
acidic metal complex bearing a moderately basic charged
counteranion would work for the generation of a nitronate
species. We envisioned that the tertiary diamine ligands
having relatively strong basicity and coordination ability
would influence the catalytic activity in the application to
the Cu(OAc)2 catalysis. Here we report a practical and useful
Henry reaction catalyzed by the new chiral diamine-Cu-
(OAc)2 complex.
derived azepine ring, resulting in narrowing of the reaction
sphere of the 2-Cu(OAc)2 catalyst. On the basis of the
structure-activity relationship described above, we designed
the new chiral diamine ligand 3, which incorporates a 1,2-
diphenylethylenediamine structure, for Cu(OAc)2 catalysis
(Figure 1).
In the design of the new ligand, one of the binaphthyl
azepine rings was replaced by a simple isoindoline to obtain
a suitable reaction sphere (Figure 1). Computational calcula-
tions with the Gaussian 03 program are presented in Figure
2.
The current study was started from the use of an analogue
2 containing more manageable 1,2-diphenylethylenediamine;
however, the 2-CuCl-catalyzed reaction of o-nitrobenzalde-
hyde with nitromethane unfortunately gave the desired
product in 98% yield with only 66% ee (24 h, rt); the yield
with a Cu(OAc)2 catalyst was 73%, with 58% ee (30 h, rt).
It was assumed that the phenyl groups of the 1,2-diphenyl-
ethylenediamine caused steric repulsion of the binaphthyl-
Figure 2. 3-Cu(OAc)2 complex (Cu: green; N: blue; O: red; C:
gray; H: white).
Optimization of geometry with the B3LYP/6-31G* method
revealed that the resulting 3-Cu(OAc)2 complex should
possess a constrained reaction sphere, allowing highly
stereocontrolled catalysis by the Cu atom. The new iso-
indoline ring stands perpendicularly to the square-planar
structure of the tetracoordinated Cu(II) complex (see Top
View in Figure 2).
The synthesis of 3 was readily carried out by a method
analogous to the synthesis of 1, using (R,R)-1,2-diphenyl-
ethylenediamine, (S)-2,2′-dibromomethyl-1,1′-binaphthalene,
and o-xylylene dibromide (see the experimental details in
the Supporting Information). Compared with the synthesis
of 1, the method used for 3 allowed a reduction in the
required amount of chiral (S)-2,2′-dibromomethyl-1,1′-bi-
naphthalene, which requires a three-step synthesis from (S)-
binaphthol.
(4) Selected examples of an enantioselective Henry reaction: (a) Sasai,
H.; Suzuki, T.; Arai, S.; Arai, T.; Shibasaki, M. J. Am. Chem. Soc. 1992,
114, 4418. (b) Christensen, C.; Juhl, C.; Jørgensen, K. A. Chem. Commun.
2001, 2222. (c) Trost, B.; Yeh, V. S. C. Angew. Chem., Int. Ed. 2002, 41,
861. (d) Evans, D. A.; Seidel, D.; Rueping, M.; Lam, H. W.; Shaw, J. T.;
Downey, C. W. J. Am. Chem. Soc. 2003, 125, 12692. (e) Kogami, Y.;
Nakajima, T.; Ashizawa, T.; Kezuka, S.; Ikeno, T.; Yamada, T. Chem. Lett.
2004, 33, 614. (f) Palomo, C.; Oiarbide, M.; Laso, A. Angew. Chem., Int.
Ed. 2005, 44, 3881. (g) Choudary, B. M.; Ranganath, K. V. S.; Pal, U.;
Kantam, M. L.; Sreedhar, B. J. Am. Chem. Soc. 2005, 127, 13167. (h)
Marcelli, T.; van der Haas, R. N. S.; van Maarseveen, J. H.; Hiemstra, H.
Angew. Chem., Int. Ed. 2006, 45, 929. (i) Mandal, T.; Samanta, S.; Zhao,
C.-G. Org. Lett. 2007, 9, 943. (j) Xiong, Y.; Wang, F.; Huang, X.; Wen,
Y.; Feng, X. Chem. Eur. J. 2007, 13, 829. (k) Ma, K.; You, J. Chem. Eur.
J. 2007, 13, 1863. (l) Bandini, M.; Piccinelli, F.; Tommasi, S.; Umani-
Ronchi, A.; Ventrici, C. Chem. Commun. 2007, 616. (m) Bandini, M.;
Benaglia, M.; Sinisi, R.; Tommasi, S.; Umani-Ronchi, A. Org. Lett. 2007,
9, 2151. See also refs 5-7.
The newly developed chiral diamine ligand 3 was utilized
in the Cu(OAc)2-catalyzed Henry reaction of o-nitrobenzal-
(5) Arai, T.; Watanabe, M.; Fujiwara, A.; Yokoyama, N.; Yanagisawa,
A. Angew. Chem., Int. Ed. 2006, 45, 5978.
3596
Org. Lett., Vol. 9, No. 18, 2007

dehyde with nitromethane. We were delighted to find that
the presence of 5 mol % of the 3-Cu(OAc)2 complex was
sufficient to provide the adduct in >99% yield with 98% ee
at room temperature (Table 1, entry 1). Because the catalyst
nitronate would cause nucleophilic addition to the activated
aldehyde, giving the (S)-nitroaldol adduct.
The catalyst was also applied to the diastereoselective
Henry reaction.6,7 As shown in Scheme 1, the reaction
Table 1. Enantioselective Henry Reaction
Scheme 1. Diastereoselective Henry Reaction
entry
R
time (h)
yield (%)b
ee (%)
1
2
o-NO2C6H4
p-NO2C6H4
C6H5
o-CH3OC6H4
BnOCH2
C6H5(CH2)2
(CH3)2CH
(CH3)2CHCH2
CH3(CH2)3
CH3(CH2)4
CH3(CH2)7
(CH3)3C
24
24
120
72
48
48
48
48
48
48
48
48
48
>99
>99
94
>99
>99
99
99
>99
95
95
94
92
96
98
93
91
95
95
>99.5
95
94
93
93
3a
4
5
6
7
8
proceeded in syn-selective manner, and both diastereomers
were obtained with excellent enantiomeric excess.
9
This syn-selectivity was in contrast with the results of
Jørgensen’s bis(oxazoline)-Cu(OTf)2-catalyzed anti-selective
Henry reaction with silyl nitronates.7b When the reaction with
1-nitropropane was carried out at 0 °C, enantiomeric excesses
of 99% were achieved for both diastereomers, although a
prolonged reaction time was required. These results indicate
that the face of the carbonyl functionality of aldehydes is
reliably selected by the chiral reaction sphere produced by
3-Cu(OAc)2.
In conclusion, we designed and developed a new chiral
diamine ligand 3. The ligand can be readily prepared by using
a cheap building block, air-stable Cu(OAc)2; the reaction is
performed in n-propyl alcohol at room temperature; and the
resulting Henry adducts are produced in high yield with
excellent enantiomeric excess. All these points contribute
to the practicality and usefulness of this catalytic system.
10
11
12
13
93
93
97
c-C6H11
a The reaction was carried out at 0 °C. b Isolated yield.
was prepared with Cu(OAc)2‚H2O, the reaction is apparently
moisture proof. Interestingly, the corresponding 3-CuCl
catalyst provided the adduct in 31% yield with only 63% ee
(72 h, rt). The broad generality of the 3-Cu(OAc)2-catalyzed
enantioselective Henry reaction is illustrated in Table 1.
The reaction was suitable not only for electron-deficient
substrates (entries 1 and 2), but also for o-methoxybenzal-
dehyde, which was converted to the corresponding adduct
in >99% yield with 95% ee (entry 4). For simple benzal-
dehyde, over 90% ee was obtained when the reaction was
carried out at 0 °C (entry 3). Moreover, aliphatic aldehydes
were smoothly converted to nitroaldols in good yields with
quite high ee (entries 5-13). In particular, the reaction of
hydrocinnamaldehyde provided the adduct quantitatively with
>99.5% ee (entry 6). R-Benzyloxy acetoaldehyde was also
applicable in the current Henry reaction, providing the
corresponding adduct with 95% ee (entry 5). The results in
Table 1 demonstrate the practical utility of the 3-Cu(OAc)2
catalyst.
Acknowledgment. This work was supported by the
Industrial Technology Research Grant Program 2006 from
the New Energy and Industrial Technology Development
Organization (NEDO) of Japan, and a Grant-in Aid for
Scientific Research from the Ministry of Education, Science,
Sports, Culture and Technology of the Japanese Government.
We thank Prof. K. Nagasawa at the Tokyo University of
Agriculture and Technology for providing the analytical data
of the diastereoselective Henry reactions.
In all reactions examined in Table 1, the product was
obtained in the (S)-form, generated by nucleophilic attack
of nitromethane at the re-face of the aldehyde. On the basis
of the Evans’ report, the acetate anion would act as a weak
base to generate a nitronate.4d Then, in the most reactive
transition states, the nitronate stands at the position of the
apical site, and the aldehyde would coordinate to the more
Lewis acidic equatorial site. In the equatorial coordination,
the site adjacent to the isoindoline ring is the most appropriate
for reducing the steric repulsion, and the bulky side chain
of the aldehyde would be released to a vacant space over
the small isoindoline ring. Subsequently, the generated
Supporting Information Available: Experimental pro-
cedure and analytical data for all new compounds. This
material is available free of charge via the Internet at
http://pubs.acs.org.
OL7014362
(6) Syn-selective asymmetric Henry reaction: (a) Sasai, H.; Tokunaga,
T.; Watanabe, S.; Suzuki, T.; Itoh, N.; Shibasaki, M. J. Org. Chem. 1995,
60, 7288. (b) Sohtome, Y.; Hashimoto, Y.; Nagasawa, K. Eur. J. Org. Chem.
2006, 2894.
(7) Anti-selective Henry reaction with silyl nitronates: (a) Ooi, T.; Doda,
K.; Maruoka, K. J. Am. Chem. Soc. 2003, 125, 2054. (b) Risgaard, T.;
Gothelf, K. V.; Jørgensen, K. A. Org. Biomol. Chem. 2003, 1, 153.
Org. Lett., Vol. 9, No. 18, 2007
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