4382
J. P. Henschke et al. / Tetrahedron Letters 44 (2003) 4379–4383
Table 1. Hydrogenation of acetophenone
Entry
Phosphine
Amine
S/C
5,000
5,000
5,000
5,000
5,000
15,000
Time (h)
Conv.d (%)
Eed (%)
1a
2a
3b
4b
5c
6c
(R)-9b
(R)-9b
(R)-9b
(S)-9b
(R)-9b
(R)-9b
(R,R)-2
(S,S)-2
(R,R)-2
(S,S)-2
(R)-3
5
5
3
3
1
2
>99
89
>99
>99
>99
>99
99 (S)
54 (S)
99 (S)
99 (R)
98 (S)
98 (S)
(R)-3
a Reactions were run at room temperature under 5 bar H2 in 50 mL magnetically stirred Parr pressure vessels.
b Reactions run at 30°C under 10 bar H2 in an overhead stirred Argonaut Endeavour multi-well pressure vessel.
c Reactions at 30°C under 10 bar H2 in 50 mL magnetically stirred Parr pressure vessels.
d Determined by chiral GC analysis (column: Chirasil DEX-CB).
phines. Such ligands play a fundamental role in what is,
at present, the most efficient and cost-effective technol-
ogy for the asymmetric reduction of a wide variety of
ketones. The ruthenium catalysts containing the new
ligand Xyl-TetraPHEMP perform in this catalysis pro-
tocol according to our best expectations. The develop-
ment of a new family of ligands based on the synthetic
strategy outlined herein will contribute to expanding
the array of tools available for asymmetric catalysis.
7. (a) Burk, M. J.; Hems, W.; Herzberg, D.; Malan, C.;
Zanotti-Gerosa, A. Org. Lett. 2000, 2, 4173–4176; (b)
Chaplin, D.; Harrison, P.; Henschke, J. P.; Lennon, I. C.;
Meek, G.; Moran, P.; Pilkington, C.; Ramsden, J. A.;
Watkins, S.; Zanotti-Gerosa, A. Org. Process Res. Dev.
2003, 7, 89–94.
8. (a) Burk, M. J.; Malan, C. PCT WO/0194359 A, 2001;
Chem. Abstr. 2001, 136, 37771; (b) Henschke, J. P.; Burk,
M. J.; Malan, C.; Herzberg, D.; Peterson, J.; Wildsmith,
A.; Cobley, C.; Casy, G. Adv. Synth. Catal. 2003, 345,
300–307.
Acknowledgements
9. Wu, J.; Chen, H.; Kwok, W.; Guo, R.; Zhou, Z.; Yeung,
C.; Chan, A. S. C J. Org. Chem. 2002, 67, 7908–7910.
10. (a) Trabesinger, G.; Albinati, A.; Feiken, N.; Kunz, R.;
Pregosin, P. S.; Tschoerner, M. J. Am. Chem. Soc. 1997,
119, 6315–6323; (b) Selvakumar, K.; Valentini, M.;
Pregosin, P. S.; Albinati, A.; Eisentra¨ger, F.
Organometallics 2000, 19, 1299–1307.
We are grateful to Dr. Christophe Malan for prelimi-
nary discussions and Natasha Cheeseman for the initial
development of analytical assays.
11. (a) Cai, D.; Payack, J. F.; Bender, D. R.; Hughes, D. L.;
Verhoeven, T. R.; Reider, P. J. J. Org. Chem. 1994, 59,
7180–7181; (b) Ager, D. J.; East, M. B.; Eisenstadt, A.;
Laneman, S. A. Chem. Commun. 1997, 2359–2360; (c)
Sayo, N.; Zhang. X.; Ohmoto, T.; Yoshida, A.;
Yokozawa, T. US Patent 5,693,868, 1997; Chem. Abstr.
1997, 127, 50792; (d) Zhang, X.; Sayo. N. US Patent
5,992,918, 1999; Chem. Abstr. 1998, 129, 16234.
12. It is worth noting that in the synthesis of H8-BINAP,
which also possesses an electron rich backbone, the phos-
phine groups cannot be introduced in one step from the
corresponding triflate, unlike the parent ligand BINAP,11
but rather, they must be introduced in a stepwise fashion.
See: Kumobayashi, H.; Miura, T.; Sayo, N.; Saito, T.;
Zhang, X. Synlett 2001, 1055–1064.
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