J. E. D. Martins et al. / Tetrahedron Letters 50 (2009) 688–692
691
Table 4
Supplementary data
Reductions of ketones 28–48 using IrCl3/chiral diaminesa
Entry
Ketone
Ligand
N-R
Conv (%)
ee (%)
General experimental details, ligands and alcohols not de-
scribed above, and 1H and 13C NMR of all new compounds. Supple-
mentary data associated with this article can be found, in the
1
2
3
4
5
6
7
8
9
28
28
28
29
29
30
30
31
31
32
32
33
33
33
33
34
34
35
36
37
37
38
39
39
40
41
42
43
44
45
45
46
46
47
47
48
18
19
20
18
20
18
20
18
20
18
20
17
18
19
20
17
20
20
20
17
20
20
16
18
20
20
20
20
20
17
20
17
20
17
20
20
(CH2)3Ph
(CH2)2Ph
n-Pr
(CH2)3Ph
n-Pr
(CH2)3Ph
n-Pr
(CH2)3Ph
n-Pr
(CH2)3Ph
n-Pr
Et
(CH2)3Ph
(CH2)2Ph
n-Pr
Et
n-Pr
n-Pr
n-Pr
Et
n-Pr
n-Pr
CH2Ph
(CH2)3Ph
n-Pr
n-Pr
n-Pr
n-Pr
n-Pr
Et
n-Pr
Et
n-Pr
Et
n-Pr
100
100
100
100
100
100
100
92
98
100
99
100
100
100
100
100
100
97
63 (S)
63 (S)
66 (S)
61 (S)
68 (S)
83 (S)
84 (S)
64 (S)
72 (S)
58 (S)
59 (S)
69 (S)
68 (S)
69 (S)
71 (S)
60 (S)
66 (S)
69 (S)
73 (S)
68 (S)
73 (S)
83 (S)
30 (S)
59 (S)
66 (S)
53 (S)
76 (S)
27 (S)
74 (S)
54 (S)
66 (S)
40 (S)
51 (S)
64 (S)
76 (S)
17 (S)
References and notes
1. (a) Noyori, R. Adv. Synth. Catal. 2003, 345, 15–32; (b) Noyori, R.; Sandoval, C. A.;
Muniz, K.; Ohkuma, T. Philos. Trans. R. Soc. A 2005, 363, 901–912; (c) Hedberg, C.
In Modern Reduction Methods; Andersson, P. G., Munslow, I. J., Eds.; Wiley-VCH,
2008. Chapter 5; (d) Noyori, R.; Kitamura, M.; Ohkuma, T. Proc. Natl. Acad. Sci.
2004, 101, 5356–5362; (e) Noyori, R.; Ohkuma, T. Angew. Chem., Int. Ed. 2006,
40, 40–73.
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
2. (a) Ohkuma, T.; Sandoval, C. A.; Srinivasan, R.; Lin, Q.; Wei, Y.; Muniz, K.;
Noyori, R. J. Am. Chem. Soc. 2005, 127, 8288–8289; (b) Doucet, H.; Ohkuma, T.;
Murata, K.; Yokozawa, T.; Katayama, E.; England, A. F.; Ikariya, T.; Noyori, R.
Angew. Chem., Int. Ed. 1998, 37, 1703–1707; (c) Ohkuma, T.; Ooka, H.;
Hashiguchi, S.; Ikariya, T.; Noyori, R. J. Am. Chem. Soc. 1995, 117, 2675–2676;
(d) Chen, C.-Y.; Reamer, R. A.; Chilenski, J. R.; McWilliams, C. J. Org. Lett. 2003, 5,
5039–5042; (e) Henschke, J. P.; Burk, M. J.; Malan, C. G.; Herzberg, D.; Peterson,
J. A.; Wildsmith, A. J.; Cobley, C. J.; Casy, G. Adv. Synth. Catal. 2003, 345, 300–
307; (f) Chaplin, D.; Harrison, P.; Henschke, J. P.; Lennon, I. C.; Meek, G.; Moran,
P.; Pilkington, C. J.; Ramsden, J. A.; Watkins, S.; Zanotti-Gerosa, A. Org. Process
Res. Dev. 2003, 7, 89–94; (g) Li, X.; Chen, W.; Hems, W.; King, F.; Xiao, J. Org.
Lett. 2003, 5, 4559–4561; (h) Burk, S.; Francio, G.; Leitner, W. Chem. Commun.
2005, 3062–3460; (i) Xu, Y.; Alcock, N. W.; Clarkson, G. J.; Docherty, G.;
Woodward, G.; Wills, M. Org. Lett. 2004, 6, 4105–4107; (j) Xie, J.-H.; Zhou, Z.-T.;
Kong, W.-L.; Zhou, Q.-L. J. Am. Chem. Soc. 2007, 129, 1868–1869; (k) Arai, N.;
Ooka, H.; Azuma, K.; Yabuuchi, T.; Kurono, N.; Inoue, T.; Ohkuma, T. Org. Lett.
2007, 9, 939–941; (l) Mikami, K.; Wakabayashi, K.; Aikawa, K. Org. Lett. 2006, 8,
1517–1519; (m) Hu, A.; Ngo, H. L.; Lin, W. Org. Lett. 2004, 6, 2937–2940; (n)
Arai, N.; Suzuki, K.; Sugizaki, S.; Sorimachi, H.; Ohkuma, T. Angew. Chem., Int. Ed.
2008, 47, 1770–1773.
3. (a) Rautenstrauch, V.; Hoang-Cong, X.; Churland, R.; Abdur-Rashid, K.; Morris,
R. H. Chem. Eur. J. 2003, 9, 4954–4967; (b) Gao, J.-X.; Ikariya, T.; Noyori, R.
Organometallics 1996, 15, 1087–1089; (c) Gao, J.-X.; Zhang, H.; Yi, X.-D.; Xu,
P.-P.; Tang, C.-L.; Wan, H.-L.; Tsai, K.-R.; Ikariya, T. Chirality 2000, 12, 383–
388; (d) Laue, S.; Greiner, L.; Woltinger, J.; Liese, A. Adv. Synth. Catal. 2001,
343, 711–720; (e) Naud, F.; Spindler, F.; Rueggeberg, C. J.; Schmidt, A. T.;
Blaser, H.-U. Org. Process Res. Dev. 2007, 11, 519–523; (f) Zhu, S.-F.; Xie, J.-B.;
Zhang, Y.-Z.; Li, S.; Zhou, Q.-L. J. Am. Chem. Soc. 2006, 128, 12886–12891.
4. (a) Li, T.; Churland, R.; Lough, A. J.; Abdur-Rashid, K.; Morris, R. H.
Organometallics 2004, 23, 6239–6247; (b) Hamilton, R. J.; Bergens, S. H. J. Am.
Chem. Soc. 2006, 128, 13700–13701; (c) Clapham, S. E.; Guo, R.; Zimmer-De
Iuliis, M.; Rasool, N.; Lough, A.; Morris, R. H. Organometallics 2006, 25, 5477–
5486.
5. Ito, M.; Hirakawa, M.; Murata, K.; Ikariya, T. Organometallics 2001, 20, 379–381.
6. (a) Ohkuma, T.; Utsumi, N.; Tsutsumi, K.; Murata, K.; Sandoval, C. A.; Noyori, R.
J. Am. Chem. Soc. 2006, 128, 8724–8725; (b) Ohkuma, T.; Tsutsumi, K.; Utsumi,
N.; Arai, N.; Noyori, R.; Murata, K. Org. Lett. 2007, 9, 255–257; (c) Sandoval, C.
A.; Ohkuma, T.; Utsumi, N.; Tsutsumi, K.; Murata, K.; Noyori, R. Chem. Asian J.
2006, 1–2, 102–110; (d) Ohkuma, T.; Utsumi, N.; Watanabe, M.; Tsutsumi, K.;
Arai, N.; Murata, K. Org. Lett. 2007, 9, 2565–2567; (e) Murata, K.; Ikariya, T.;
Noyori, R. J. Org. Chem. 1999, 64, 2186–2187; (f) Thorpe, T.; Blacker, J.; Brown, S.
M.; Bubert, C.; Crosby, J.; Fitzjohn, S.; Muxworthy, J. P.; Williams, J. M. J.
Tetrahedron Lett. 2001, 42, 4041–4043; (g) Heiden, Z. M.; Gorecki, B. J.;
Rauchfuss, T. B. Organometallics 2008, 27, 1542–1549.
7. (a) Hedberg, C.; Kallstrom, K.; Arvidsson, P. I.; Brandt, P.; Andersson, P. G. J. Am.
Chem. Soc. 2005, 127, 15083–15090; (b) Samec, J. S. M.; Bäckvall, J.-E.;
Andersson, P. G.; Brandt, P. Chem. Soc. Rev. 2006, 35, 237–248; (c)
Paptchikhine, A.; Kaellstroem, K.; Andersson, P. G. C.R. Chim. 2007, 10, 213–219.
8. (a) Jones, M. D.; Raja, R.; Thomas, J. M.; Johnson, B. F. G.; Lewis, D. W.; Rouzard,
J.; Harris, K. D. M. Angew. Chem., Int. Ed. 2003, 42, 4231–4326; (b) Raja, R.;
Thomas, J. M.; Jones, M. D.; Johnson, B. F. G.; Vaughan, D. E. W. J. Am. Chem. Soc.
2003, 125, 14982–14983. based on a precedent by de Rege, F. M.; Morita, D. K.;
Ott, K. C.; Tumas, W.; Broene, R. D. Chem. Commun. 2000, 1797–1798.
9. Haung, H.; Okuno, T.; Tsuda, K.; Yoshimura, M.; Kitamura, M. J. Am. Chem. Soc.
2006, 128, 8716–8717.
73
100
100
100
100
100
100
100
100
100
100
100
100
100
100
94
100
100
n-Pr
a
Conditions: 1 mol % catalyst (ligand:Ir(III) 1:1), NaOH: catalyst = 30:1,
[ketone] = 1 M, MeOH, 50 bar hydrogen, 40 °C, 24 h.
The use of the trans-diamine ligand is also important; the cis-
derivative of 18, that is, ligand 54, gave reduction of acetophenone
12 in 73% yield and just 7% ee and reduction of ketone 29 in only
24% yield and 2% ee.
In conclusion, we have demonstrated that the combination of
Ir(III)Cl3 with an alkylated TsDPEN derivative results in the forma-
tion of a competent catalyst for asymmetric ketone hydrogenation.
In the best cases and for certain substrates (e.g., 30, 37, 38), the lev-
els of enantiomeric excess obtained are comparable with those ob-
tained using more complex catalysts. The catalysts benefit from
simplicity of preparation; the ligands are typically prepared in
one step by reductive alkylation of commercially-available TsDPEN
(see Supplementary data). Additionally, the most basic of precious
metal salts is required for the preparation of the catalysts. Our
observations suggest that a 1:1 diamine:Ir(III) complex is formed,
however, we are continuing to work towards gaining an under-
standing of the mechanism and the use of further catalyst
derivatives.
10. (a) Sandoval, C. A.; Ohkuma, T.; Muniz, K.; Noyori, R. J. Am. Chem. Soc. 2003, 125,
13490–13503; (b) Abdur-Rashid, K.; Faatz, M.; Lough, A. J.; Morris, R. H. J. Am.
Chem. Soc. 2001, 123, 7473–7474; (c) Abdur-Rashid, K.; Clapham, S. E.;
Hadzovic, A.; Harvey, J. N.; Lough, A. J.; Morris, R. H. J. Am. Chem. Soc. 2002,
124, 15104–15118; (d) Hartmann, R.; Chen, P. Angew. Chem., Int. Ed. 2001, 40,
3581–3585; (e) Abbel, R.; Abdur-Rashid, K.; Faatz, M.; Hadzovic, A.; Lough, A.
J.; Morris, R. H. J. Am. Chem. Soc. 2005, 127, 1870–1882; (f) Hamilton, R. J.;
Leong, C. G.; Bigam, G.; Miskolzie, M.; Bergens, S. H. J. Am. Chem. Soc. 2005, 127,
4152–4153; (g) Leysson, T.; Peters, D.; Harvey, J. N. Organometallics 2008, 27,
1514–1523.
Acknowledgements
We thank the EPSRC for financial support of DJM (EPSRC Project
Grant No. EP/D031168/1), Coordenação de Aperfeiçoamento de
Pessoal de Ensinol Superior (CAPES, Brazil) for a scholarship to
JEDM. Dr B. Stein and colleagues of the EPSRC National Mass Spec-
troscopic service (Swansea) are thanked for HRMS analysis of cer-
tain compounds. We acknowledge the use of the EPSRC Chemical
Database Service at Daresbury.26
11. Ter Halle, R.; Breheret, A.; Schulz, E.; Pinel, C.; Lemaire, M. Tetrahedron:
Asymmetry 1997, 8, 2101–2108.
12. Wu, X.; Corcoran, C.; Yang, S.; Xiao, J. ChemSusChem 2008, 1, 71–74.