Asymmetric cyanohydrin formation from aldehydes catalyzed by manganese Schiff base complexes

Article abstract of DOI:10.1016/j.tetasy.2010.01.009

The catalyst generated in situ from Mn(OAc)₂ and a chiral Schiff base ligand exhibited excellent catalytic abilities in asymmetric cyanohydrin formation from aldehydes with sodium cyanide in up to 99% enantioselectivity and good yield.

Full text of DOI:10.1016/j.tetasy.2010.01.009

Tetrahedron: Asymmetry 21 (2010) 187–190
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Tetrahedron: Asymmetry
journal homepage: www.elsevier.com/locate/tetasy
Asymmetric cyanohydrin formation from aldehydes catalyzed by manganese
Schiff base complexes
Yanyang Qu , Linhai Jing , Zhiqing Wu , Di Wu a,b, Xiangge Zhou a,b,
a
a
a
*
a
Institute of Homogeneous Catalysis, College of Chemistry, Sichuan University, Chengdu 610064, China
State Key Laboratory of Coordination Chemistry, Nanjing University, Nanjing 210093, China
b
a r t i c l e i n f o
a b s t r a c t
Article history:
Received 23 November 2009
Accepted 15 January 2010
The catalyst generated in situ from Mn(OAc)2 and a chiral Schiff base ligand exhibited excellent catalytic
abilities in asymmetric cyanohydrin formation from aldehydes with sodium cyanide in up to 99% enanti-
oselectivity and good yield.
Ó 2010 Elsevier Ltd. All rights reserved.
1
. Introduction
The cyanohydrin formationreaction isone ofthe fundamentalcar-
hyde was selected as the model substrate by using manganese(II)
acetate and ligand 1 as the catalyst, and the results are listed in
Table 1.
In order to investigate this water-soluble catalytic system, the
1
bon–carbon bond-forming reactions in organic chemistry. Optical
cyanohydrins can usuallybeused asversatile synthonsto forma wide
reaction was first carried out in water. However, regardless of
the addition of phase transfer catalyst (PTC) or not, low ee
values (<6%) together with low yields were obtained (Table 1,
entries 1–4). Thus, other solvents including some mixed solvents
were used in catalysis, and methanol was shown to be the most
favourable one with up to 97% ee (Table 1, entries 5–16). The dos-
age of catalyst was also examined, and the results indicated any
more than 0.2 mol % of catalyst was not necessary with quite stable
enantioselectivities around 96% (Table 1, entries 17–19). Further-
more, the ee values were only slightly affected by the reaction time
(entries 11 and 12).
variety of important chiral compounds such as
a
-amino acids,
-hydroxy
ketones. In the last few decades, a range of catalysts has been devel-
a-hy-
droxy carboxylic acids, b-amino alcohols, vicinal diols and
a
2
3
4
oped for this reaction including enzymes, cyclic dipeptides, chiral
Lewis acids/bases and chiral transition metal complexes. For exam-
ple, catalytic systems generated from titanium(IV), aluminium(III),
5
,6
7
8
9
10
vanadium(V), some lanthanide metal salts and chiral ligands have
been successfully applied in the asymmetric trimethylsilylcyanation
of aldehydes with good results. Enzymes and peptides have also been
successfully used in the catalytic addition of HCN to aldehydes with
high enantiomeric excesses.11 However, difficulties in handling the
expense of trimethylsilyl cyanide and the volatility of hydrogen
cyanide together with strict reaction conditions severely limit their
applications. Efforts to employ other catalysts and utilize inexpensive
and easily manipulated cyanide sources under mild reaction condi-
tions would still be worthy of study in the asymmetric synthesis of
cyanohydrins, and there have been recently reported examples using
In order to study the actual catalytic species formed during the
reaction, the complex formed by Mn(OAc)
lated and proven to be a Mn(III) species as reported.
2
and ligand 1 was iso-
18a
It was also
used as catalyst with 65% yield and 97% ee, which was almost the
same as the in situ-generated catalyst (entry 11). Thus, the isola-
1
2–15
sodium cyanide in the catalytic cyanation of aldehydes.
As a
continuation of our recent work in catalytic reactions by water-solu-
ble salen complexes, we herein report asymmetric cyanohydrin
formation from aldehydes with sodium cyanide catalyzed by
in situ-generated sulfonato manganese salen complexes under mild
reaction conditions.
N
N
R2
R2
OH HO
2
. Results and discussion
R1
R1
Schiff base ligands 1–3 shown in Figure 1 were prepared and
used in this work. To optimize the reaction conditions, benzalde-
1
2
L1 = R = H, R = -SO3Na
1
2
L2 = R = t-Bu, R = SO3Na
1
2
L3 = R = R = t-Bu
*
Corresponding author. Tel./fax: +86 28 85412026.
E-mail address: zhouxiangge@scu.edu.cn (X. Zhou).
Figure 1. Ligands 1–3 evaluated in this study.
0
957-4166/$ - see front matter Ó 2010 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetasy.2010.01.009

1
88
Y. Qu et al. / Tetrahedron: Asymmetry 21 (2010) 187–190
Table 1
by manganese(II) acetate and ligand 2 was proven to be superior
than others.
Finally, the substrates were expanded to a range of aldehydes
2
by using catalyst in situ formed from ligand 2 and Mn(OAc) under
Screening the reaction conditions of cyanohydrin formation from benzaldehyde with
sodium cyanidea
O
OH
Mn(OAc)2-Ligand 1
the optimized reaction conditions. The results are listed in Table 3.
In general, the catalyst formed in situ from manganese(II) acetate
and ligand 2 exhibited good to excellent catalytic abilities for the
cyanohydrination of benzaldehyde and analogues. The positions of
the substituents seemed to have a greater influence on the results
than the electronic effects. For example, both 4-methylbenzalde-
hyde and 4-nitrobenzaldehyde afforded 97% and 93% ees, respec-
tively (Table 3, entries 1 and 6), while 2-nitrobenzaldehyde
afforded only 66% ee (Table 3, entry 8). The highest enantioselectiv-
ities of 99% was obtained by using 4-chlorobenzaldehyde and
+
NaCN
CN
Solvent, rt
Entry
Catalyst (%)
PTC (%)
Solvent b
Yield (%)
eec (%)
1
2
3
4
5
6
7
8
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
—
10
20
50
—
—
—
—
—
—
—
—
—
—
—
—
—
—
—
H
H
H
H
H
H
H
H
H
2
2
2
2
2
2
2
2
2
O
O
O
O
10
12
24
47
12
31
40
35
17
62
67
20
30
12
38
65
62
52
60
5
5
4
6
O/CH
O/CH
O/THF
O/DMF
O/CH
3
CN
Cl
10
14
5
2
2
a-naphthaldehyde (Table 3, entries 3 and 11). However, aliphatic
aldehydeswere notsuitablefor this catalyticsystemwith lowee val-
ues (Table 3, entries 12 and 13).
3
1
1
0
3
OH
56
96
97
52
20
18
16
96
96
52
76
1
CH
CH
3
OH
OH
d
1
2
3
1
3
4
5
6
7
8
EtOH
i-PrOH
t-BuOH
3
. Conclusions
1
1
1
1
1
1
In conclusion, we have demonstrated the catalyst formed in situ
n-BuOH
0.5
0.2
0.1
0.2
CH
3
CH
3
CH
3
CH
3
OH
OH
OH
OH
by manganese(II) acetate and sulfonato-salen ligand 2 to be highly
efficient catalyst for the asymmetric addition of sodium cyanide to
aldehydes. Excellent chiral induction (up to 99% ee) was achieved
by using only 0.2 mol % of catalyst. In addition, the present proce-
dure for the cyanohydrination reaction has several other advanta-
ges including air-tolerance, mild reaction conditions and high
stereochemical control with a relatively wide range of substrates.
A mechanistic study is now currently underway.
9
e
2
0
a
The reactions were conducted with benzaldehyde (1 mmol) and NaCN
1.5 mmol) in 3 mL solvent at room temperature for 24 h. PTC: tetrabutylammo-
nium bromide.
(
b
The mixed solvent was composed of two different solvents in a volume ratio of
1
:1.
c
Determined by chiral GC after derivatization with acetic acid anhydride, abso-
lute configuration was (R) by comparison of the reported specific rotation (see Ref.
1
6).
4. Experimental section
d
The reaction time is 48 h.
Under inert gas N instead of opening to air.
2
e
Caution: Many of the following experimental procedures in-
volve the use of sodium cyanide, which is highly toxic and should
only be handled in a well-ventilated fume-cupboard and in compli-
ance with all relevant safety protocols.
tion of the complex for catalysis was not necessary. Catalysis under
inert gas instead of air was also carried out with lower enantiose-
lectivity of 76% (entry 20).
Under the optimized reaction conditions, two other modified li-
gands together with some other transition metal salts were tested
in this reaction, and the results are summarized in Table 2.
Chiral ligands 1, 2 and 3 were prepared as previously de-
1
8,19
scribed.
Aliphatic and aromatic aldehydes were purified by
usual methods. Optical rotations were measured in an WZZ-2B
automatic polarimeter (readability ±0.001). Chromatography was
carried out by using silica gel (300–400 mesh). All solvents were
used as commercially available.
Table 2
Screening ligands and metal salts in the cyanohydrin formation from benzaldehyde
with sodium cyanidea
4.1. Typical procedure for cyanohydrin formation from
aldehyde
Entry
Ligand
Metallic salt
Yield (%)
eeb (%)
1
2
3
4
5
L
L
L
L
L
1
1
1
2
3
Mn(OAc)
FeCl
VOSO
Mn(OAc)
Mn(OAc)
2
62
15
22
68
21
96
85
90
98
83
To a solution of the salen ligand (1.2 mg, 0.002 mmol) and
Mn(OAc) (0.5 mg, 0.002 mmol) in methanol (3 mL) was added
2
3
4
the aldehyde (1 mmol). The mixture was stirred at room tempera-
ture for 30 min. Next, NaCN (73.5 mg, 1.5 mmol) was added and
the mixture was stirred at the same temperature for 24 h. The sol-
vent was then evaporated. The product was purified by flash chro-
matography (hexane/ethyl acetate, 9:1) to give pure cyanohydrin.
The enantiomeric excess of the product was determined by chiral
HPLC or GC after conversion to the corresponding acetates by reac-
2
2
a
The reactions were conducted with 1 mmol of benzaldehyde and 1.5 mmol of
NaCN in the presence of ligand (0.2 mol %) and metallic salt (0.2 mol %) in 3 mL
methanol at room temperature for 24 h.
Determined by chiral GC after derivatization with acetic acid anhydride, the
absolute configuration was assigned by comparison with the literature data and
b
was found to be (R) (see Ref. 16).
tion with 2 equiv of acetic acid anhydride and pyridine in CH
2 2
Cl
(
5 mL) at room temperature for 12 h.
As shown in Table 2, both the ligand structure and the central
metal exhibited important effects on the catalysis. The sulfo group
which was para to the hydroxyl group of the phenyl ring seemed to
exert a major role during the catalysis especially on the chemical
yields (Table 2, entries 4 and 5). Meanwhile, the R1 group had few-
er effects on the results (Table 2, entries 1 and 4). Other metals
including Fe(III) and V(IV) were also tested with good ee values
but low yields (Table 2, entries 2 and 3). Thus, the catalyst formed
4.2. Preparation of sulfonato-salen ligands
Ligands 1–3 were prepared as previously described:18,19 diso-
dium salicylaldehyde 5-sulfonates (20 mmol) were reacted with
(R,R)-1,2-cyclohexenediamine (1.14 g, 10 mmol), respectively, in
methanol (25 mL) at 70 °C for 2 h. The reaction mixture was then
cooled to 0 °C to afford a yellow precipitate; after filtration and

Y. Qu et al. / Tetrahedron: Asymmetry 21 (2010) 187–190
189
Table 3
Asymmetric addition of sodium cyanide to various aldehydes catalyzed by ligand 2 and Mn(OAc)
a
2
Entry
Substrate
Product
Yield (%)
67
eeb (%) (config)
OH
H3C
CHO
1
CN
97 (R)
H3C
OH
H3CO
CHO
2
3
4
5
CN
45
68
55
65
91 (R)
>99 (R)
98 (R)
83 (R)
H CO
3
OH
Cl
Br
F
CHO
CN
CN
Cl
Br
F
OH
CHO
OH
CHO
CN
OH
O N
CHO
2
6
7
8
CN
60
54
42
93 (R)
89 (R)
66 (R)
O N
2
O
H
OH
CN
H3CO
H3CO
O
OH
H
CN
NO2
O
NO2
OH
9
H
CN
44
69
81 (R)
95 (R)
Cl
O
Cl
OH
1
0
1
H
H
CN
CN
N
O
N
HO
1
56
>99 (R)
H
CN
1
2
3
35
68
38 (R)
12 (R)
O
H
OH
CN
O
OH
1
a
The reactions were carried out by using aldehyde (1 mmol) and NaCN (1.5 mmol) in the presence of ligand (0.2 mol %) and manganese acetate (0.2 mol %) in 3 mL
methanol at room temperature for 24 h.
b
Determined by chiral HPLC on a Chiralcel OD column or GC after derivatization with acetic acid anhydride, absolute configuration was assigned by comparison of the sign
1
6,17,20–24
of the specific rotation with that of the literature (see Refs.
).

1
90
Y. Qu et al. / Tetrahedron: Asymmetry 21 (2010) 187–190
washing by cold methanol, yellow solids L
yields ranging from 85% to 92%.
1
–L
3
were obtained in
8. (a) Kim, S. S.; Song, D. H. Eur. J. Org. Chem. 2005, 1777–1780; (b) Zhou, Z. H.;
Zeng, Z. B.; Zhou, G. F.; Tang, C. C. Eur. J. Org. Chem. 2008, 1615–1618.
9.
(a) Belokon, Y. N.; North, M.; Parsons, T. Org. Lett. 2000, 2, 1617–1619; (b)
Belokon, Y. N.; Maleev, V. I.; North, M.; Usanov, D. L. Chem. Commun. 2006,
4614–4616.
Acknowledgements
1
0. (a) Vale, G. A.; Faustino, W. M.; Mezenes, P. H. Chem. Commun. 2006, 3340–
342; (b) Yabu, K.; Masumoto, S.; Yamasaki, S.; Hamashima, Y.; Kanai, M.; Du,
W.; Curran, D. P.; Shibasaki, M. J. Am. Chem. Soc. 2001, 123, 9908–9909.
3
This project was supported by grants from the Natural Science
Foundation of China (Nos. 20672075, 20771076, 20901052) and
Sichuan Provincial Foundation (08ZQ026-041).
11. Griengle, H.; Hickel, A.; Johnson, D. V.; Kratky, C.; Schmidt, M.; Schwab, H.
Chem. Commun. 1997, 1933–1939.
12. Belokon, Y. N.; Gutnov, A. V.; Moskalenko, M. A.; Yashkina, L. V.; Lesovoy, D. E.;
Ikonnikov, N. S.; Larichev, V. S.; North, M. Chem. Commun. 2002, 244–245.
13. For a preliminary report of some of this work see: Belokon, Y. N.; Carta, P.;
References
North, M. Lett. Org. Chem 2004, 1, 81–83.
1
4. Belokon, Y. N.; Carta, P.; Gutnov, A. V.; Maleev, V.; Moskalenko, M. A.; Yashkina,
L. V.; Ikonnikov, N. S.; Voskoboev, N. V.; Khrustalev, V. N.; North, M. Helv. Chim.
Acta 2002, 85, 3301–3312.
5. Belokon, Y. N.; Blacker, A. J.; Clutterbuck, L. A.; Hogg, D.; North, M.; Reeve, C.
Eur. J. Org. Chem. 2006, 4609–4617.
1
.
For general reviews of cyanohydrin synthesis, see: (a) Gregory, R. J. H. Chem.
Rev. 1999, 99, 3649–3682; (b) North, M. Tetrahedron: Asymmetry 2003, 14, 147–
1
76; (c) Brunel, J. M.; Holmes, I. P. Angew. Chem., Int. Ed. 2004, 43, 2752–2778.
1
2
.
(a) Griengl, H.; Hickel, A.; Johnson, D. V.; Kratky, C.; Schmidt, M.; Schwab, H.
Chem. Commun. 1997, 1933–1940; (b) Tanaka, K.; Mori, A.; Inoue, S. J. Org.
Chem. 1990, 55, 181–185.
1
6. Ognyaanov, V. I.; Datcheva, V. K.; Kyler, K. S. J. Am. Chem. Soc. 1991, 113, 6992–
6996.
3
.
.
Han, S.; Chen, P.; Lin, G.; Huang, H.; Li, Z. Tetrahedron: Asymmetry 2001, 12,
1
7. Yang, W. B.; Fang, J. M. J. Org. Chem. 1998, 63, 1356–1359.
8
43–846.
1
8. (a) Bhattacharjee, S.; Dines, T. J.; Anderson, J. A. J. Catal. 2004, 225, 398–407; (b)
Choudary, B. M.; Ramani, T.; Mahesuaran, H.; Pra-shant, L.; Ranganath, K. V. S.;
Vijaykumar, K. Adv. Synth. Catal. 2006, 348, 493–498; (c) Tan, R.; Yin, D. H.; Yu,
N. Y.; Tao, L.; Fu, Z. H.; Yin, D. L. J. Mol. Catal. A: Chem. 2006, 259, 125–132.
9. (a) Larrow, J. F.; Jacobsen, E. N. J. Org. Chem. 1994, 59, 1939–1942; (b)
Darensbourg, D. J.; Mackiewicz, R. M.; Rodgers, J. L.; Fang, C. C.; Billodeaux, D.
R.; Reibenspies, J. H. Inorg. Chem. 2004, 43, 6024–6034.
4
(a) Bolm, C.; Muller, P. Tetrahedron Lett. 1995, 36, 1625–1628; (b) Belokon, Y.;
Flego, M.; Ikonnikov, N.; Moscalenko, M.; North, M.; Orizu, C.; Tararov, V.;
Tasinazzo, M. J. Chem. Soc., Perkin Trans. 1 1997, 1293–1295; (c) Tararov, V. I.;
Hibbs, D. E.; Hursthouse, M. B.; Ikonnikov, N. S.; Malik, K. M. A.; North, M.;
Orizu, C.; Belokon, Y. N. Chem. Commun. 1998, 387–388; (d) Iovel, I.; Popelis, Y.;
Fleisher, M.; Lukevics, E. Tetrahedron: Asymmetry 1997, 8, 1279–1285.
(a) Tian, S. K.; Deng, L. J. Am. Chem. Soc. 2001, 123, 6195–6196; (b) Tian, S. K.;
Hong, R.; Deng, L. J. Am. Chem. Soc. 2003, 125, 9900–9901; (c) Tian, S. K.; Chen,
Y.; Hang, J.; Tang, L.; Mcdaid, P.; Deng, L. Acc. Chem. Res. 2004, 37, 621–631; (d)
North, M.; Usanov, D. L.; Young, C. Chem. Rev. 2008, 108, 5146–5226.
1
5
.
2
2
0. Zeng, B. Q.; Zhou, X.; Liu, X. H.; Feng, X. M. Tetrahedron 2007, 63, 5129–5136.
1. Matthews, B. R.; Jackson, W. R.; Jayatilake, G. S.; Wilshire, C.; Jacobs, H. A. Aust.
J. Chem. 1988, 41, 1697–1709.
2. Khan, N. H.; Agrawal, S.; Kureshy, R. I.; Abdi, S. H. R.; Mayani, V. J.; Jasra, R. V.
Tetrahedron: Asymmetry 2006, 17, 2659–2666.
3. Deardorff, D. R.; Taniguchi, C. M.; Nelson, A. C.; Pace, A. P.; Kim, A. J.; Pace, A. K.;
Jones, R. A.; Tafti, S. A.; Nguyen, C.; O’Connor, C.; Tang, J.; Chen, J. Tetrahedron:
Asymmetry 2005, 16, 1655–1661.
2
6
7
.
.
Li, Y.; He, B.; Qin, B.; Feng, X.; Zhang, G. J. Org. Chem. 2004, 69, 7910–7913.
(a) Hamashima, Y.; Kanai, M.; Shibasaki, M. J. Am. Chem. Soc. 2000, 122, 7412–
2
7
413; (b) Liang, S.; Bu, X. R. J. Org. Chem. 2002, 67, 2702–2704; (c) Chen, F. X.;
Feng, X. M.; Qin, B.; Zhang, G. L.; Jiang, Y. Z. Org. Lett. 2003, 5, 949–952; (d) He,
B.; Chen, F. X.; Li, Y.; Feng, X. M.; Zhang, G. L. Eur. J. Org. Chem. 2004, 4657–
2
4. Hayashi, M.; Miyamoto, Y.; Inoue, T.; Oguni, N. J. Org. Chem. 1993, 58, 1515–
4
1
666; (e) Jiang, Y.; Gong, L.; Feng, X.; Hu, W.; Pan, W.; Li, Z.; Mi, A. Tetrahedron
997, 53, 14327–14338.
1522.