5
388
D. Guijarro et al. / Tetrahedron Letters 50 (2009) 5386–5388
O
S
2010, CSD2007-00006 and CTQ200765218) and the Generalitat
Valenciana (GV/2007/036). O.P. thanks the University of Alicante
for a predoctoral fellowship. We also thank MEDALCHEMY S.L.
for a gift of chemicals.
N
But
i,ii
NH2
R
Ar
R
Ar
1
2
a: Ar = Ph, R = Me
b: Ar = Ph, R = Et
References and notes
1.
(a) Noyori, R.; Hashiguchi, S. Acc. Chem. Res. 1997, 30, 97–102; (b) Palmer, M. J.;
Wills, M. Tetrahedron: Asymmetry 1999, 10, 2045–2061; (c) Wang, C.; Wu, X.;
Xiao, J. Chem. Asian J. 2008, 3, 1750–1770.
c: Ar = 4-MeOC H , R = Me
6
4
d: Ar = 4-O NC H , R = Me
2
6
4
2.
See, for instance: (a) Kobayashi, S.; Ishitani, H. Chem. Rev. 1999, 99, 1069–1094;
Scheme 2. Reagents and conditions: (i) [RuCl
2
2
(p-cymene)] (cat.), (1S,2R)-1-amino-
(
b) Helmchen, G.; Pfaltz, A. Acc. Chem. Res. 2000, 33, 336–345; (c) Kitamura, M.;
i
2
-indanol (cat.), base (cat.), 4 Å molecular sieves (0.5 g), Pr OH, T; (ii) HCl, MeOH.
Noyori, R. Ruthenium Org. Synth. 2004, 3–52; (d) Wills, M. In Modern Reduction
Methods; Andersson, P. G., Munslow, I. J., Eds.; Wiley-VCH: Weinheim, 2008; pp
2
71–296.
t
3. (a) Ellman, J. A.; Owens, T. D.; Tang, T. P. Acc. Chem. Res. 2002, 35, 984–995; (b)
Ellman, J. A. Pure Appl. Chem. 2003, 75, 39–46; (c) Zhou, P.; Chen, B.-C.; Davis, F.
A. Tetrahedron 2004, 60, 8003–8030; (d) Lin, G.-Q.; Xu, M.-H.; Zhong, Y.-W.;
Sun, X.-W. Acc. Chem. Res. 2008, 41, 831–840; (e) Ferreira, F.; Botuha, C.;
Chemla, F.; Pérez-Luna, A. Chem. Soc. Rev. 2009, 38, 1162–1186.
Ru-dimer:L3:Bu OK = 1:2:5 in further experiments. The amount of
the ruthenium complex was also varied to 8 and 3 mol %. The use
of 8 mol % of the catalyst reduced the reaction time to 5 h keeping
the excellent yield and enantioselectivity (Table 2, entry 8). With
4.
See, for instance: (a) Sun, X.; Wang, S.; Sun, S.; Zhu, J.; Deng, J. Synlett 2005,
776–2780; (b) Kosciolowicz, A.; Rozwadowska, M. D. Tetrahedron: Asymmetry
3
mol % of the catalyst, the reaction time was much longer than
2
with 5 mol % of it, which was accompanied by a reduction of the
yield to 84% (Table 2, entry 9).
2006, 17, 1444–1448; (c) Denolf, B.; Mangelinckx, S.; Toernroos, K. W.; De
Kimpe, N. Org. Lett. 2006, 8, 3129–3132.
5
.
(a) Chelucci, G.; Baldino, S.; Chessa, S.; Pinna, G. A.; Soccolini, F. Tetrahedron:
Asymmetry 2006, 17, 3163–3169; (b) Zhao, C.-H.; Liu, L.; Wang, D.; Chen, Y.-J.
Eur. J. Org. Chem. 2006, 2977–2986; (c) Dutheuil, G.; Couve-Bonnaire, S.;
Pannecoucke, X. Angew. Chem., Int. Ed. 2007, 46, 1290–1292; (d) Grajewska, A.;
Rozwadowska, M. D. Tetrahedron: Asymmetry 2007, 18, 557–561; (e) Han, Z.;
Koenig, S. G.; Zhao, H.; Su, X.; Singh, S. P.; Bakale, R. P. Org. Process Res. Dev.
The influence of the temperature was also studied. Increasing the
temperature of the reduction process to 40 °C led to a considerable
reduction in the reaction time to only 2 h, giving a quantitative yield
of amine 2a with a very slight decrease in the ee (Table 2, entry 10).
Another attempt to reduce the amount of catalyst to 3 mol % was
done in a reaction at 40 °C. The reaction time was quite short (4 h),
but again a reduced yield was obtained (Table 2, entry 11).
After performing the optimisation of the reaction conditions,
2007, 11, 726–730; (f) Liu, Z.-J.; Liu, J.-T. Chem. Commun. 2008, 5233–5235.
6. (a) Colyer, J. T.; Andersen, N. G.; Tedrow, J. S.; Soukup, T. S.; Faul, M. M. J. Org.
Chem. 2006, 71, 6859–6862; (b) Denolf, B.; Leemans, E.; De Kimpe, N. J. Org.
Chem. 2007, 72, 3211–3217; (c) Peltier, H. M.; Ellman, J. A. J. Org. Chem. 2005,
7
0, 7342–7345; (d) Tanuwidjaja, J.; Peltier, H. M.; Ellman, J. A. J. Org. Chem.
1
1
some other imines 1b–d were used as substrates (Scheme 2, Table
, entries 12–14). All the reactions were carried out at 40 °C in order
2007, 72, 626–629.
7
.
.
Xiao, X.; Wang, H.; Huang, Z.; Yang, J.; Bian, X.; Qin, Y. Org. Lett. 2006, 8, 139–
2
142.
12
to have short reduction times. Imine 1b, derived from propiophe-
none, gave an excellent yield and enantioselectivity in a reaction
time of 4 h (Table 2, entry 12). The methodology is equally efficient
for the reduction of phenone-derived imines bearing either an elec-
tron-withdrawing or an electron-releasing group on the aromatic
ring. Very high yields and ee’s were obtained irrespective of the elec-
tronic nature of the aromatic ring of the imine (Table 2, entries 13
and 14).
8
(a) Almansa, R.; Guijarro, D.; Yus, M. Tetrahedron: Asymmetry 2008, 19, 603–
606; (b) Almansa, R.; Guijarro, D.; Yus, M. Tetrahedron: Asymmetry 2008, 19,
2484–2491; (c) Almansa, R.; Guijarro, D.; Yus, M. Tetrahedron Lett. 2009, 50,
3198–3201; (d) Almansa, R.; Guijarro, D.; Yus, M. Tetrahedron Lett. 2009, 50,
4188–4190.
9. (a) Almansa, R.; Guijarro, D.; Yus, M. Tetrahedron: Asymmetry 2007, 18, 896–
8
2
99; (b) Almansa, R.; Guijarro, D.; Yus, M. Tetrahedron: Asymmetry 2007, 18,
828–2840; (c) Almansa, R.; Guijarro, D.; Yus, M. Tetrahedron: Asymmetry 2008,
1
9, 1376–1380.
10. The enantiomer of ligand L3 has successfully been applied to the asymmetric
transfer hydrogenation of ketones. See: Wills, M.; Palmer, M.; Smith, A.; Kenny,
J.; Walsgrove, T. Molecules 2000, 5, 4–18.
1. All the imines 1 were prepared according to a literature procedure: Liu, G.;
Cogan, D. A.; Owens, T. D.; Tang, T. P.; Ellman, J. A. J. Org. Chem. 1999, 64, 1278–
1284.
It is worth noting that, in our previous studies, we could not
prepare amine 2a in good yields by addition of a trimethylzincate
to N-(tert-butanesulfinyl)benzaldimine due to the slow transfer
rate of the methyl group.8 Therefore, this transfer hydrogenation
process can be considered as complementary to the addition of
triorganozincates to the sulfinylimines.
1
1
2. Typical experimental procedure (Table 2, entry 10): ligand L3 (14 mg,
0
.09 mmol) was dissolved in benzene (1 mL) and the solvent was
evaporated. This process was repeated two more times, after which [RuCl (p-
cymene)] (28 mg, 0.045 mmol), 4 Å molecular sieves (0.5 g) and anhydrous
2
In conclusion, we have presented here a new and very efficient
procedure to prepare optically pure primary amines through the
highly diastereoselective reduction of N-(tert-butanesulfi-
nyl)imines by a ruthenium-catalysed transfer hydrogenation pro-
cess. The careful removal of all possible moisture allows the
reduction of the imine to proceed very efficiently in short reaction
times. To the best of our knowledge, this is the first time that the
asymmetric transfer hydrogenation of an acyclic imine in isopropa-
2
i
Pr OH (2 mL) were added and the reaction mixture was heated up to 90 °C (oil
bath temperature) for 20 min. During this heating period, the initially orange
reaction mixture turned into a dark red colour. The reaction was then cooled to
i
t
40 °C and a solution of imine 1a (0.9 mmol) in Pr OH (9 mL) and Bu OK
(
i
2.25 mL of a 0.1 M solution in Pr OH, 0.225 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 residue
that was directly submitted to the desulfinylation step, which was carried out
following the procedure previously described by us (see Ref. 8b). The absolute
configuration of the asymmetric carbon atom of the major enantiomer was
determined by comparison of the sign of the specific rotation of the free amine
2a with the reported data. The enantiomeric excess was determined for the
corresponding benzamide by HPLC as previously described by us (see Ref. 8b).
3. Bäckvall has reported the non-stereoselective ruthenium-catalysed transfer
1
3,14
nol using a b-aminoalcohol as chiral ligand has been reported.
Further efforts to extend the substrate scope and to find more syn-
thetic applications of this reduction methodology are currently
underway in our laboratories.
1
2 3
hydrogenation of imines in refluxing isopropanol in the presence of K CO :
Acknowledgements
Wang, G.-Z.; Bäckvall, J.-E. J. Chem. Soc., Chem. Commun. 1992, 980–982.
1
4. Andersson has reported the synthesis of chiral aziridines by a ruthenium-
catalysed asymmetric transfer hydrogenation of strained 2H-azirines in
isopropanol using a b-aminoalcohol as a chiral ligand: Roth, P.; Andersson, P.
G.; Somfai, P. Chem. Commun. 2002, 1752–1753.
This work was generously supported by the Spanish Ministerio
de Educación y Ciencia (MEC; Grant Nos. CONSOLIDER INGENIO