Bernsmann et al.
Monodentate phosphonites, phosphites, and phosphor-
amidites have the advantage of being readily accessible,
highly diverse in structure, and extraordinarily inexpen-
sive compared to various bidentate ligands. MonoPhos
(1A), one of the simplest members of the monodentate
phosphoramidite ligand family based on a BINOL back-
bone and first synthesized 10 years ago,21 has proven to
be an excellent ligand in the asymmetric rhodium-cat-
alyzed hydrogenation of dehydroamino acids and esters,
aromatic enamides, and itaconic acid derivatives showing
enantioselectivities comparable to the most successful
bidentate ligands.11
After its disclosure, closely related ligands were re-
ported which with some substrates surpass 1A in enan-
tioselectivity.22 To be synthetically versatile, however, ee’s
of 99% or higher are required, especially when the
products are oils and recrystallization to raise the ee is
prohibited. In addition, several more challenging sub-
strates require further improvement of the MonoPhos
ligand structure. Ideally, for a chiral catalyst tool kit the
ligands should be readily available, yet highly diverse,
allowing the production of a true ligand library.23,24
Herein, we report the synthesis of a focused library of
monodentate phosphoramidites and their application in
the rhodium-catalyzed asymmetric hydrogenation of N-
acyldehydroamino esters, itaconic acid derivatives, and
N-acyl enamides. Two new privileged ligands, PipPhos
FIGURE 1. Examples of effective ligands in asymmetric
hydrogenation of 2-acetamidocinnamic acid or its ester.
(13) For recent examples with other monodentate phosphorus
ligands, see: (a) Huang, H.; Zheng, Z.; Luo, H.; Bai, C.; Hu, X.; Chen,
H. Org. Lett. 2003, 5, 4137. (b) Hua, Z.; Vassar, V. C.; Ojima, I. Org.
Lett. 2003, 5, 3831. (c) Hannen, P.; Militzer, H.-C.; Vogel, E. M.; Rampf,
F. A. Chem. Commun. 2003, 2210. (d) Ostermeier, M.; Brunner, B.;
Korff, C.; Helmchen, G. Eur. J. Org. Chem. 2003, 3453. (e) Junge, K.;
Oehme, G.; Monsees, A.; Riermeier, T.; Dingerdissen, U.; Beller, M.
Tetrahedron Lett. 2002, 43, 4977. (f) Ostermeier, M.; Prieâ, J.;
Helmchen, G. Angew. Chem., Int. Ed. 2002, 41, 612. (g) Guillen, F.;
Rivard, M.; Toffano, M.; Legros, J.-Y.; Daran, J.-C.; Fiaud, J.-C.
Tetrahedron 2002, 58, 5895. (h) Chen, W.; Xiao, J. Tetrahedron Lett.
2001, 42, 8737. (i) Chen, W.; Xiao, J. Tetrahedron Lett. 2001, 42, 2897.
(j) Reetz, M. T.; Mehler, G.; Meiswinkel, A.; Sell, T. Tetrahedron Lett.
2002, 43, 7941. (k) Huang, H.; Zheng, Z.; Luo, H.; Bai, C.; Hu, X.; Chen,
H. J. Org. Chem. 2004, 69, 2355.
(14) (a) Pen˜a, D.; Minnaard, A. J.; De Vries, J. G.; Feringa, B. L. J.
Am. Chem. Soc. 2002, 124, 14552. (b) Jerphagnon, T.; Renaud, J. L.;
Demonchaux, P.; Ferreira, A.; Bruneau, C. Adv. Synth. Catal. 2004,
346, 33. (c) ref 13k.
(15) Reetz, M. T.; Goossen, L. J.; Meiswinkel, A.; Paetzold, J.;
Feldthusen Jensen, J. Org. Lett. 2003, 5, 3099.
(16) Junge, K.; Oehme, G.; Monsees, A.; Riermeier, T.; Dingerdissen,
U.; Beller, M. J. Organomet. Chem. 2003, 675, 91.
ites11 have been successfully applied in the enantiose-
lective rhodium-catalyzed hydrogenation of N-acyl-R-
dehydroamino acids and esters, itaconic acid deriva-
tives,12,13 N-acylenamides,7,13 and recently N-acyl-â-de-
hydroamino esters14 and vinylcarboxylates.15 Further-
more, other monodentate phosphorus ligands such as
aminophosphinites,16 diazaphospholidines,17 secondary
phosphine oxides18 and polymer-supported, heterog-
enized, or dendritic phosphoramidites19 have been de-
veloped and successfully applied in asymmetric hydro-
genations. A recent study showed that a number of
monodentate ligands not only show comparable or higher
enantioselectivities than state-of-the-art bidentate ligands
but also can compete in terms of reaction rates.20
(9) (a) Claver, C.; Fernandez, E.; Gillon, A.; Heslop, K.; Hyett, D.
J.; Martorell, A.; Orpen A. G.; Pringle, P. G. Chem. Commun. 2000,
961. (b) Reetz, M. T.; Sell, T. Tetrahedron Lett. 2000, 41, 6333.
(10) Reetz, M. T.; Mehler, G. Angew. Chem., Int. Ed. 2000, 39, 3889.
(11) Van den Berg, M.; Minnaard, A. J.; Schudde, E. P.; Van Esch,
J.; De Vries, A. H. M.; De Vries, J. G.; Feringa, B. L. J. Am. Chem.
Soc. 2000, 122, 11539.
(17) Reetz, M. T.; Oka, H.; Goddard, R. Synthesis 2003, 1809.
(18) (a) Jiang, X.-b.; Minnaard, A. J.; Hessen, B.; Feringa, B. L.;
Duchateau, A. L. L.; Andrien, J. G. O.; Boogers, J. A. F.; De Vries, J.
G. Org. Lett. 2003, 5, 1503. (b) Jiang, X.-b.; Van den Berg, M.;
Minnaard, A. J.; Feringa, B. L.; De Vries, J. G. Tetrahedron: Asymmetry
2004, 15, 2223. (c) Reetz, M. T.; Sell, T.; Goddard, R. Chimia 2003,
57, 290.
(12) For recent results with phosphoramidites, see: (a) Van den
Berg, M.; Minnaard, A. J.; Haak, R. M.; Leeman, M.; Schudde, E. P.;
Meetsma, A.; Feringa, B. L.; De Vries, A. H. M.; Maljaars, C. E. P.;
Willans, C. E.; Heytt, D.; Boogers, J. A. F.; Henderickx, H. J. W.; De
Vries, J. G. Adv. Synth. Catal. 2003, 345, 308. (b) Jia, X.; Li, X.; Xu,
L.; Shi, Q.; Yao, X.; Chan, A. S. C. J. Org. Chem. 2003, 68, 4539. (c)
Van den Berg, M.; Minnaard, A. J.; De Vries, J. G.; Feringa, B. L. (DSM
N.V.), World Patent WO 02/04466, 2002. (d) Van den Berg, M.; Haak,
R. M.; Minnaard, A. J.; De Vries, A. H. M.; De Vries, J. G.; Feringa, B.
L. Adv. Synth. Catal. 2002, 344, 1003. (e) Zeng, Q.; Liu, H.; Mi, A.;
Jiang, Y.; Li, X.; Choi, M. C. K.; Chan, A. S. C. Tetrahedron 2002, 58,
8799. (f) Zeng, Q.; Liu, H.; Cui, X.; Mi, A.; Jiang, Y.; Li, X.; Choi, M. C.
K.; Chan, A. S. C. Tetrahedron: Asymmetry 2002, 13, 115. (g) Fu, Y.;
Xie, J.-H.; Hu, A.-G.; Zhou, H.; Wang, L.-X.; Zhou, Q.-L. Chem.
Commun. 2002, 480. (h) Li, X.; Jia, X.; Lu, G.; Au-Yeung, T. T.-L.;
Lam, K.-H.; Lo, T. W. H.; Chan, A. S. C. Tetrahedron: Asymmetry 2003,
14, 2687. (i) Jia, X.; Guo, R.; Li, X.; Yao, X.; Chan, A. S. C. Tetrahedron
Lett. 2002, 43, 5541. (j) Hu, A.-G.; Fu, Y.; Xie, J.-H.; Zhou, H.; Wang,
L.-X.; Zhou, Q.-L. Angew. Chem., Int. Ed. 2002, 41, 2348. (k) Wu, S.;
Zhang, W.; Zhang, Z.; Zhang, X. Org. Lett. 2004, 6, 3565.
(19) (a) Doherty, S.; Robins, E. G.; Pa´l, I.; Newman, C. R.; Hardacre,
C.; Rooney, D.; Mooney, D. A. Tetrahedron: Asymmetry 2003, 14, 1517.
(b) Wang, X.; Ding, K. J. Am. Chem. Soc. 2004, 126, 10524. (c) Botman,
P. N. M.; Amore, A.; Van Heerbeek, R.; Back, J. W.; Hiemstra, H.;
Reek, J. N. H.; Van Maarseveen, J. H. Tetrahedron Lett. 2004, 45, 5999.
(20) Pen˜a, D.; Minnaard, A. J.; De Vries, A. H. M.; De Vries, J. G.;
Feringa, B. L. Org. Lett. 2003, 5, 475.
(21) Hulst, R.; De Vries, N. K.; Feringa, B. L. Tetrahedron: Asym-
metry 1994, 5, 699.
(22) Reference 12e,f. Ligand 5A has been reported to lead to
enhanched ee’s in some cases: Reetz, M. T. Chim. Oggi-Chem. Today
2003, 21 (10-11), 5.
(23) De Vries, J. G.; De Vries, A. H. M. Eur. J. Org. Chem. 2003,
799.
(24) (a) Lefort, L.; Boogers, J. A. F.; De Vries, A. H. M.; de Vries, J.
G. Org. Lett. 2004, 6, 1733. (b) Duursma, A.; Lefort, L.; Boogers, J. A.
F.; De Vries, A. H. M.; De Vries, J. G.; Minnaard, A. J.; Feringa, B. L.
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944 J. Org. Chem., Vol. 70, No. 3, 2005