Asymmetric Transfer Hydrogenation of Sulfinylimines
FULL PAPER
Cierva contract to G.K.) and the Generalitat Valenciana (PROMETEO/
2009/039 and FEDER). O.P. thanks the Spanish Ministerio de Educaciꢃn
for a predoctoral fellowship (grant no. AP-2008–00989). We also thank
MEDALCHEMY S.L. for a gift of chemicals.
Experimental Section
General procedure for the asymmetric transfer hydrogenation of imines
1: A mixture of [{RuCl2(para-cymene)}2] (14 mg, 0.023 mmol), the ligand
L
(4 mg, 0.045 mmol), molecular sieves (4 ꢆ, 0.4 g), and anhydrous
iPrOH (1.3 mL) was heated to 908C (oil bath temperature) for 20 min.
During this heating period, the initially orange reaction mixture turned
dark red in color. The reaction was then cooled to 508C and a solution of
the imine 1 (0.9 mmol) in iPrOH (6.3 mL) and tBuOK (0.1m solution in
iPrOH, 1.13 mL, 0.113 mmol) were successively added. After completion
of the reaction (monitored by TLC), the reaction mixture was passed
through a small column of silica gel, the column was washed with ethyl
acetate and the combined organic phases were evaporated to give a resi-
due that was directly submitted to the desulfinylation step.[51]
Lawrence, Amines: Synthesis, Properties and Applications, Cam-
bridge University Press, Cambridge, 2004; c) T. C. Nugent, M. El-
Shazly, Adv. Synth. Catal. 2010, 352, 753–819.
[2] M. Breuer, K. Ditrich, T. Habicher, B. Hauer, M. Keßeler, R.
[3] J. Jacques, A. Collet, S. H. Wilen, Enantiomers, Racemates and Reso-
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Vilaivan, W. Bhanthumnavin, Y. Sritana-Anant, Curr. Org. Chem.
1205–1227; d) F. Spindler, H.-U. Blaser in Handbook of Homogene-
ous Hydrogenation, Vol. 3 (Eds.: J. G. De Vries, C. J. Elsevier),
Wiley-VCH, Weinheim, 2007, pp. 1193–1214; e) C. Claver, E.
Fernꢂndez in Modern Reduction Methods (Eds.: P. G. Andersson,
I. J. Munslow), Wiley-VCH, Weinheim, 2008, pp. 237–269.
[6] M. Wills in Modern Reduction Methods (Eds.: P. G. Andersson, I. J.
Munslow), Wiley-VCH, Weinheim, 2008, pp. 271–296.
b) S. A. Westcott, R. T. Baker in Modern Reduction Methods (Eds.:
P. G. Andersson, I. J. Munslow), Wiley-VCH, Weinheim, 2008,
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[8] T. Yamada, T. Nagata, K. D. Sugi, K. Yorozu, Y. Ohtsuka, D. Miya-
General procedure for the removal of the sulfinyl group: Isolation of
amines 2: The crude mixture from the transfer hydrogenation reaction
was dissolved in a solution of HCl in methanol (1.5m, 4 mL; prepared by
dropwise addition of SOCl2 to methanol at 08C) and stirred overnight at
room temperature. The solvent was then evaporated off, an aqueous solu-
tion of HCl (2m, 5 mL) was added and the mixture was extracted with
ethyl acetate (3ꢈ5 mL). The organic layers were discarded. The aqueous
layer was basified with a buffer solution of NH3 (1m)/NH4Cl (1m) and
extracted with CH2Cl2 (3ꢈ10 mL). The combined organic layers were
then dried (Na2SO4). After filtration and evaporation of the solvent, pure
amines 2 were obtained in the yields and ee values indicated in Table 2.
The corresponding physical and spectroscopic data for the representative
compound 2n follows:
(R)-1-(4-Nitrophenyl)ethanamine (2n):[52] Yellow oil; Rf =0.20 (ethyl ace-
tate, deactivated silica gel); [a]2D0 = +12.5 (c=1.0 in CHCl3, 98% ee) [lit-
erature [a]2D4 for ent-2n=ꢁ16.0 (c=0.76 in CHCl3, 96% ee)]; 1H NMR
(300 MHz, CDCl3, 258C, TMS): d=8.17 (d, J=8.8 Hz, 2H), 7.54 (d, J=
8.8 Hz, 2H), 4.26 (q, J=6.7 Hz, 1H), 1.64 (brs, 2H), 1.40 ppm (d, J=
6.7 Hz, 3H); 13C NMR (75 MHz, CDCl3, 258C): d=155.1, 146.7, 126.6,
123.6, 50.8, 25.7 ppm; IR (neat): n˜ =1346, 1516, 1597, 3075, 3215,
3370 cmꢁ1; MS (70 eV): m/z (%): 166 (<1) [M+], 151 (100), 105 (30), 104
(13).
[9] O. Riant in Modern Reduction Methods (Eds.: P. G. Andersson, I. J.
Munslow), Wiley-VCH, Weinheim, 2008, pp. 321–337.
(Eds.: P. G. Andersson, I. J. Munslow), Wiley-VCH, Weinheim,
2008, pp. 341–361; c) T. Marcelli, P. Hammar, F. Himo, Chem. Eur.
[12] See, for instance: a) X. Wu, C. Wang, J. Xiao, Platinum Met. Rev.
2010, 54, 3–19; b) X. Wu, J. Xiao in Handbook of Green Chemistry,
Vol. 5 (Eds.: P. T. Anastas, C.-J. Li), Wiley-VCH, Weinheim, 2010,
pp. 105–149.
[13] See, for instance: a) K. B. Hansen, J. R. Chilenski, R. Desmond,
P. N. Devine, E. J. J. Grabowski, R. Heid, M. Kubryk, D. J. Mathre,
Blacker, J. Martin in Asymmetric Catalysis on Industrial Scale (Eds.:
H. U. Blaser, E. Schmidt), Wiley-VCH, Weinheim, 2004, pp. 201–
216; c) J. Whittall in Catalysts for Fine Chemical Synthesis: Regio-
and Stereo-Controlled Oxidations and Reductions, Vol. 5 (Eds.: S. M.
Roberts, J. Whittall), Wiley, New York, 2007, pp. 1–33.
Computational Details: [Ru(para-cymene)(2-amino-2-methylpropan-1-
ol)] was the catalyst, and the N-(tert-butylsulfinyl)ketimine 1a, derived
from acetophenone, was chosen as the substrate for the theoretical calcu-
lations. No simplification was made in any of the reactant molecules se-
lected for the computational study. The geometry optimizations were car-
ried out by DFT calculations with the program package Gaussian 09[53]
and the M06[54] functional. The SDD[55] pseudo-potential was employed
for the ruthenium center, and the standard 6–31GACTHNUTRGNEUNG
(d,p)[56] basis set was
used for the other atoms. Energies were calculated by means of single-
point calculations by using the same SDD pseudo-potential for the metal
center and the extended 6–311+ +GACTHNUTRGENUGN(d,p) basis set for the other atoms.
The effect of the bulk solvent (isopropyl alcohol, IPA) was estimated by
the application of the polarizable continuum model (PCM)[57] as imple-
mented in Gaussian 09 [eACTHNUTRGNEUG(N IPA)=19.264]. All energies given in the text
correspond to those including the effect of the bulk solvent, which was
obtained by adding the contribution of the Gibbs energy of solvation to
the gas-phase total energies. In the case of the transition states, normal
coordinate analysis was used to calculate the imaginary frequencies, and
for each transition structure we calculated the intrinsic reaction coordi-
nate (IRC) routes towards the corresponding minima. If the IRC calcula-
tions failed to reach the energy minima on the potential energy surface,
we performed geometry optimizations from the final phase of the IRC
path.
[15] M. Kitamura, R. Noyori in Ruthenium in Organic Synthesis (Ed.: S.-
I. Murahashi), Wiley-VCH, Weinheim, 2004, pp. 3–52.
nefeld, J. A. Peteers in Handbook of Homogeneous Hydrogenation
(Eds.: J. G. de Vries, C. J. Elsevier), Wiley-VCH, Weinheim, 2007;
Lledꢃs in Advances in Inorganic Chemistry, Vol. 62: Theoretical and
Acknowledgements
This work was generously supported by the Spanish Ministerio de Cien-
cia e Innovaciꢃn (MICINN; grant no. CONSOLIDER INGENIO 2010,
CSD2007–00006, CTQ2007–65218, CTQ2011–23336, and a Juan de la
Chem. Eur. J. 2012, 18, 1969 – 1983
ꢅ 2012 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
1981