A novel organocatalytic asymmetric transfer hydrogenation of α,β-unsaturated aldehydes

Article abstract of DOI:10.1002/hlca.201300029

α,β-Unsaturated aldehydes reacted with diimide (diazene) in the presence of optically active ammonium salt 1 as a catalyst to give the corresponding saturated aldehydes in excellent yields and up to 98: 2 er. Attractive features of the asymmetric transfer hydrogenation are its high yields, and chemo-, and enantioselectivities.

Full text of DOI:10.1002/hlca.201300029

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Helvetica Chimica Acta – Vol. 96 (2013)
A Novel Organocatalytic Asymmetric Transfer Hydrogenation of a,b-
Unsaturated Aldehydes
by Bao-Hua Zhang, Lan-Xiang Shi*, and Rui-Xia Guo
College of Chemical Engineering, Shijiazhuang University, Shijiazhuang 050035, P. R. China
(phone: þ 86-311-66617320; e-mail: kedashilanxiang@126.com)
a,b-Unsaturated aldehydes reacted with diimide (diazene) in the presence of optically active
ammonium salt 1 as a catalyst to give the corresponding saturated aldehydes in excellent yields and up to
98 :2 er. Attractive features of the asymmetric transfer hydrogenation are its high yields, and chemo-, and
enantioselectivities.
Introduction. – Asymmetric catalytic hydrogenations are used in large-scale
industrial production of pharmaceuticals and fine chemicals. Metal-catalyzed hydro-
genations are the most frequently used catalytic asymmetric processes. But their
disadvantage is the need of complete removal of metal impurities from the reaction
product in order to meet the quality requirements of pharmaceutical intermediates [1].
Organocatalysis is free of metals and, therefore, of increased interest [2]. Here, we
report on a chiral ammonium salt, 1, which effectively catalyze the asymmetric transfer
hydrogenation of a,b-unsaturated aldehydes 2 with diimide (diazene; 3).
Results and Discussion. – We found that treating aromatic, trisubstituted a,b-
unsaturated aldehyde 2 with diimide (3; produced in situ from potassium diazene-1,2-
dicarboxylate (KO2CN¼NCO2K) and glacial AcOH) and a catalytic amount of chiral
ammonium salt 1 in THF at room temperature, the corresponding saturated aldehydes
4 were obtained in high yields and excellent enantioselectivities (Table).
We also investigated the influence of the configuration at the C¼C bond.
Remarkably, when we subjected both the isolated pure (E)- and (Z)-isomers of 3-
NO2 derivative 2c to our reaction conditions, the same (R)-enantiomer of product 4c
was obtained with the same enantiomeric ratio (er) of 98 :2. Similarly, (E)-2c/(Z)-2c
mixtures always gave the same result, and, independent of their exact ratio, all
furnished (R)-4c with er of 98 :2. Thus, our process is enantioconvergent, a highly
desirable yet rare feature of a catalytic asymmetric reaction, where a mixture of
stereoisomers furnishes only one product enantiomer. Carbonyl reduction or aldoliza-
tion products were not detected.
Mechanistically, we assume that the reaction takes place by formation of iminium
ion 5, which presumably isomerizes quickly via dienamine 6 (Scheme). The following
rate-determining hydride transfer from diimide 3 to enal (E)-5 via transition state A
proceeds faster than to (Z)-5 (kE > kZ) and, as a result, saturated aldehyde (R)-4 is
formed predominantly.
ꢀ 2013 Verlag Helvetica Chimica Acta AG, Zꢁrich

Helvetica Chimica Acta – Vol. 96 (2013)
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Table. Organocatalytic Asymmetric Transfer Hydrogenation of a,b-Unsaturated Aldehydes
Entry
R
Product
Yield [%]
er
1
2
3
Ph
4a
4b
4c
79
91
96 : 4
97: 3
98 : 2
98 : 2
98 : 2
97: 3
98 : 2
96 : 4
4-ClꢀC6H4
3-O2NꢀC6H4
85 (from (E)-2c)
80 (from (Z)-2c)
82 (from (E)-2c/(Z)-2c 1 : 1)
89
83
85
4
5
6
4-NCꢀC6H4
4d
4e
4f
4-F3CꢀC6H4
Naphthalen-2-yl
Scheme. Proposed Mechanism of the Organocatalytic Asymmetric Transfer Hydrogenation
Conclusions. – The reaction of a,b-unsaturated aldehydes and diimide (¼diazene)
in the presence of catalytic amounts of (2R,5R)-1 is a highly efficient asymmetric
transfer hydrogenation. Attractive features of the process are high yields, chemo- and
enantioselectivities, and simplicity. Applications in the synthesis of natural products,
pharmaceuticals, and fine chemicals can be envisaged.

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Helvetica Chimica Acta – Vol. 96 (2013)
Experimental Part
General. The starting materials, aldehydes 2a – 2f, and potassium diazene-1,2-dicarboxylate
(KO2CN¼NCO2K) were synthesized as described in [3] and [4], resp. (2R,5R)-2,5-Dibenzylpyrrolidine
was synthesized as described in [5]. Gas chromatography (GC): Agilent 7890A gas chromatograph.
Optical rotations: WZZ-2B digital polarimeter. 1H- and 13C-NMR spectra: Bruker Avance 400
spectrometer. Elemental analyses: Vario EL III instrument.
General Procedure for the Preparation of Chiral Ammonium Salt 1. To a soln. of (2R,5R)-
dibenzylpyrrolidine (251 mg, 1.0 mmol) in Et2O (5 ml) was added glacial AcOH (132 mg, 2.2 mmol) with
stirring. The salt 1 precipitated immediately. It was filtered and washed with Et2O.
Data of 1. 1H-NMR (300 MHz, CDCl3): 1.50 – 2.10 (m, CH2CH2), 2.99 (dd, J ¼ 7, 13, PhCH2), 3.54
(dd, J ¼ 7, 13, PhCH2), 3.80 – 4.10 (m, 2 CH), 7.20 (s, 10 arom. H). MS: 252 ([M þ H]þ), 251 (Mþ), 160
([M ꢀ CH2Ph]þ). Anal. calc for C18H21N · AcOH: C 77.20, H 8.11, N 4.52; found: C 77.12, H 8.03, N 4.50.
General Procedure for the Asymmetric Transfer Hydrogenation. To a stirred solution of a a,b-
unsaturated aldehyde 2 (0.5 mmol) in THF (10 ml) at r.t. were added catalyst 1 (15.5 mg, 0.05 mmol,
10 mol-%), potassium diazene-1,2-dicarboxylate (114 mg, 0.6 mmol) and pyridine (94.8 mg, 1.2 mmol),
and, after 5 min, AcOH (72 mg, 1.2 mmol) was slowly added dropwise. After 48 h, the mixture was
poured into dist. H2O (20 ml) and extracted with CH2Cl2 (2 ꢁ 15 ml). The combined org. layers were
dried (MgSO4), filtered, and concentrated. The product was isolated by flash chromatography (SiO2;
AcOEt/hexane) to give the saturated aldehyde 4. The absolute configuration of (R)-4 was determined by
measurement of their optical rotation and comparison with the literature value [3][6]. Enantiomeric
ratio (er) was determined by chiral-stationary-phase GC analysis.
This study was supported by the Chinaꢀs Hebei Province Science and Technology Support Project
(No.13964002D) and the Shijiazhuang University Project (No. XJPT007).
REFERENCES
[1] C. E. Garrett, K. Prasad, Adv. Synth. Catal. 2004, 346, 889.
[2] P. I. Dalko, L. Moisan, Angew. Chem. 2001, 113, 3840; P. I. Dalko, L. Moisan, Angew. Chem., Int. Ed.
2001, 40, 3726.
`
[3] R. Martꢂn, I. Islas, A. Moyano, M. A. Pericas, A. Riera, Tetrahedron 2001, 57, 6367; M. I. Al-Hassan,
Gazz. Chim. Ital. 1985, 115, 441; M. Akhtar, L. Jallo, A. Johnson, J. Chem. Soc., Chem. Commun.
1982, 44; A. I. Meyers, A. Nabeya, H. W. Adickes, J. M. Fitzpatrick, G. R. Malone, I. R. Politzer, J.
Am. Chem. Soc. 1969, 91, 764.
[4] D. J. Pasto, R. T. Taylor, Organic Reactions, L. A. Paquethe, John Wiley & Sons, New York, 1991,
Vol. 40, p. 91.
[5] M. Nakajima, K. Tomioka, K. Koga, Tetrahedron 1993, 49, 9735.
[6] T. Lee, J. B. Jones, J. Am. Chem. Soc. 1997, 119, 10260.
Received January 15, 2013