Mixtures of configurationally stable and fluxional atropisomeric monodentate P ligands in asymmetric Rh-catalyzed olefin hydrogenation

Article abstract of DOI:10.1002/anie.200462612

(Chemical Equation Presented) Mixed (pre)catalysts such as 1 arise when [Rh(cod)₂]BF₄ is combined with a 1:1 mixture of a BINOL-derived monodentate phosphonite or phosphite ligand and a configurationally fluxional atropisomeric phosp

Full text of DOI:10.1002/anie.200462612

Angewandte
Chemie
Combinatorial Catalysis
Mixtures of Configurationally Stable and
Fluxional Atropisomeric Monodentate P Ligands
in Asymmetric Rh-Catalyzed Olefin
Hydrogenation**
Manfred T. Reetz* and Xiaoguang Li
Several years ago it was reported that monodentate phos-
phites,[1] phosphonites,[2] and phosphoramidites[3] derived
from 2,2’-dihydroxy-1,1’-binaphthyl (BINOL) are efficient
ligands in various Rh-catalyzed asymmetric olefin-hydro-
genation reactions (90–99% ee). These observations were
surprising, because it had been accepted that chelating
bidentate P ligands are generally necessary for high levels
of enantioselectivity, probably due to restricted rotation in the
Rh complexes. Examples of other types of monodentate P
ligands are also known.[4] Preliminary mechanistic results
show that two monodentate phosphites (or phosphonites) are
bonded to Rh in the transition state of hydrogenation[5] when
the precatalyst is [Rh(cod)(1)2]BF4 (cod = cycloocta-1,5-
diene). Based on these results we subsequently demonstrated
that the use of a mixture of two different monodentate P
ligands constitutes a new and efficient approach to combina-
torial asymmetric transition-metal catalysis.[6] Once a library
[*] Prof. Dr. M. T. Reetz, Dr. X. Li
Max-Planck-Institut fꢀr Kohlenforschung
Kaiser-Wilhelm-Platz 1, 45470 Mꢀlheim/Ruhr (Germany)
Fax: (+49)208-306-2985
E-mail: reetz@mpi-muelheim.mpg.de
[**] Generous support by the Fonds der Chemischen Industrie is
gratefully acknowledged.
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DOI: 10.1002/anie.200462612
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Table 1: Rh-catalyzed hydrogenation of olefin 3a.[a] (R)-BINOL deriva-
tives led to (S)-4a.
of cheap ligands has been prepared, mixtures result in high
catalyst diversity and new ligands are not needed. Although
each system actually contains three (pre)catalysts in an (as
yet) unpredictable ratio, namely the two homocombinations
[Rh(cod)LaLa]BF4 and [Rh(cod)LbLb]BF4, as well as the
heterocombination [Rh(cod)LaLb]BF4, enantioselectivities of
95–99% ee are often possible, even though the respective
homocombinations in pure form result in lower enantiose-
lectivities. Mixtures of BINOL-derived P ligands in combi-
nation with a phosphinine (phosphabenzene) or triphenyl-
phosphine cause reversal of enantioselectivity in a few cases.[7]
Entry
Ligand
Conv. [%]
ee [%]
Homocombinations
1
2
1a
1b
95
83
75
45
Heterocombinations
3
4
5
6
7
1a/6
1a/7
1a/8
1a/9
1a/10
1a/11
1a/2a
1a/2b
1a/2c
1a/2d
1b/5
1b/6
1b/7
1b/8
1b/9
1b/10
1b/11
1b/2a
1b/2b
1b/2c
1b/2d
51
92
100
96
100
84
83
92
57
97
46
67
98
99
100
89
50
14
30
30
81
79
73
67
83
65
51
17
5
84
16
45
88
98
98
7
8
9
10
11
12
13
14
15
16
17
18
19
20
21
22
23
91
We now show that mixtures of appropriate chiral BINOL-
derived phosphonites such as (R)-1b in combination with
certain achiral P ligands or configurationally fluxional atrop-
isomeric phosphites 2 derived from the corresponding achiral
biphenols are also excellent ligand systems.
100
100
10
99
94
[a] Conditions: 60 bar H2, CH2Cl2, RT, 20 h, Rh/3a=1:50; La/Lb =1:1;
Rh/total ligands=1:2).
phonite (R)-1b alone leads to only 45% ee (S) (entry 2),
whereas the heterocombination of (R)-1b and achiral 11
results in 88% ee (S) (entry 19). Selectivities higher than
those obtained with the homocombinations were also
observed for several other heterocombinations (entries 7, 8,
11, 16). Dramatic effects emerged when heterocombinations
of phosphonite (R)-1b and configurationally labile atropiso-
meric phosphites 2a, 2b, and 2d were used; these systems
lead to enantioselectivities of 98% ee (S), 98% ee (S), and
94% ee (S), respectively (entries 20, 21, 23).
A preliminary NMR study of the precatalyst system
derived from (R)-1b and 2a indicates the existence of a
mixture of the two expected homocombinations [Rh-
(cod)((R)-1b)2]BF4 and [Rh(cod)(2a)2]BF4 in addition to
the heterocombination [Rh(cod)(R)-1b(2a)]BF4 in a ratio of
about 1:1:16 (plus a small amount of unidentified species).
However, the situation is in fact more complicated, because
those complexes containing the configurationally labile
atropisomeric 2a actually exist as fluxional diastereomers.
Thus, the major component in the above mixture exists as a
pair of diastereomers in equilibrium [Eq. (2)]. They inter-
convert so rapidly even at low temperatures that their relative
amounts cannot be measured by NMR spectroscopy. In the
extreme case only one diastereomeric form is present, but this
is rather unlikely.
Our model reaction was the Rh-catalyzed hydrogenation
of b-acylamino acrylate 3a with formation of the b-amino acid
derivative 4a [Eq. (1)][8] In addition to 2, the achiral
phosphines PMe3 (5), PiPr3 (6), and PPh3 (7) as well as the
achiral phosphites P(OMe)3 (8), P(OiPr3)3 (9), P(OCH2tBu)3
(10), and P(OPh)3 (11) were used in combination with (R)-1b
(or (R)-1a). In all cases [Rh(cod)2]BF4 was treated with a 1:1
mixture of the two monodentate P ligands (Rh/ligands = 1:2)
prior to hydrogenation under standard conditions.[8]
½RhðcodÞ ðRÞ-1 b ðRÞ-2 aꢀBF4 Ð ½RhðcodÞ ðRÞ-1 b ðSÞ-2 aꢀBF4
ð2Þ
Some remarkable results are listed in Table 1. In partic-
ular, the homocombination comprising the tert-butylphos-
We postulate that diastereomer [Rh(cod)(R)-1b(R)-
2a]BF4 constitutes the matched case; cooperativity leads to
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a higher hydrogenation rate and to enhanced enantioselec-
tivity. To lend support to this hypothesis, we prepared and
tested separately the structurally related heterocombinations
composed of two BINOL-derived building blocks, namely
[Rh(R)-1b(R)-1a]BF4 and [Rh(R)-1b(S)-1a]BF4, which are
configurationally stable diastereomeric complexes. We have
already shown that the former precatalyst leads to 99% ee
(S),[8] and we now note that the latter is considerably less
effective (40% ee (S); 84% yield). Of course, it must be
remembered that these catalysts cannot be prepared in pure
form; in other words, in each case it is the mixture of the two
respective homocombinations and the heterocombination
that defines the catalytic profile and thus determines the
observed enantioselectivity.
[1] a) M. T. Reetz, G. Mehler, Angew. Chem. 2000, 112, 4047 – 4049;
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2001.
[2] a) M. T. Reetz, T. Sell, Tetrahedron Lett. 2000, 41, 6333 – 6336;
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[3] M. van den Berg, A. J. Minnaard, E. P. Schudde, J. van Esch,
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Chi, X. Zhang, Tetrahedron Lett. 2002, 43, 4849 – 4852; e) W.
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The result of our combinatorial search[9] suggested that
the heterocombination of 1b and 2a may be the optimal
ligand system for Rh-catalyzed hydrogenations of b-acyl-
amino acrylates in general. Therefore this combination was
tested in the hydrogenation of the other substrates 3b–e
under standard conditions. Indeed, excellent results were
obtained: 3b (96% ee (S); 90% yield), 3c (95% ee (S); 90%
yield), 3d (97% ee (S); 94% yield;), 3e (84% ee (R); 69%
yield).
Finally, we performed the hydrogenation of itaconic acid
diester 12 (Rh/12 = 1:1000; Rh/ligand = 1:2; 1.3 bar H2; RT;
20 h) using the homocombination (R)-1b, which resulted in
only 77% ee (R) [80% yield, Eq. (3)). For this reason we
turned to the corresponding mixtures: The combinations (R)-
1b/2a and (R)-1b/11 gave essentially identical enantioselec-
tivities (94% ee (R)) and quantitative yield.
[5] A. Meiswinkel, Dissertation, Ruhr-Universitꢁt Bochum, Ger-
many, 2003.
[6] a) M. T. Reetz, T. Sell, A. Meiswinkel, G. Mehler, Angew. Chem.
2003, 115, 814 – 817; Angew. Chem. Int. Ed. 2003, 42, 790 – 793;
b) M. T. Reetz, Chim. Oggi 2003, 21, 5 – 8; see also: c) D. Peꢂa,
A. J. Minnaard, J. A. F. Boogers, A. H. M. de Vries, J. G. de V-
ries, B. L. Feringa, Org. Biomol. Chem. 2003, 1, 1087 – 1089.
[7] M. T. Reetz, G. Mehler, Tetrahedron Lett. 2003, 44, 4593 – 4596.
[8] M. T. Reetz, X. Li, Tetrahedron 2004, 60, 9709 – 9714 and
literature cited therein concerning previous work on the hydro-
genation of 3.
[9] The data shown here constitutes only about half of the total
combinatorial search. Combinations of phosphonite 1 (X = CH3)
with 2 or 5–11 do not result in positive effects.
In summary, we have shown for the first time that in Rh-
catalyzed olefin-hydrogenation, mixtures comprising
a
BINOL-derived P ligand in combination with an achiral P
compound, or a BINOL-derived P ligand in combination with
a chiral but configurationally fluxional biphenol-derived
phosphite can result in high enantioselectivity. The latter
system is most effective and involves two rapidly intercon-
verting diastereomers; the presumably more reactive R/R
combination shows higher activity and enantioselectivity than
the diastereomeric R/S form. Apart from the theoretical
interest, the present results are of practical importance
because half of the ligand system is derived from cheap
achiral compounds such as biphenol.[10] It remains to be seen
if this combinatorial approach can be extended to other
reactions and ligand types.[11,12]
[10] We have previously shown that certain diphosphites composed
of a chiral backbone diol and fluxional atropisomeric biphenol
derivatives provide selectivities of up to 99% ee in olefin
hydrogenation; three rapidly interconverting diastereomers are
involved: a) M. T. Reetz, T. Neugebauer, Angew. Chem. 1999,
111, 134 – 137; Angew. Chem. Int. Ed. 1999, 38, 179 – 181;
b) D. G. Blackmond, T. Rosner, T. Neugebauer, M. T. Reetz,
Angew. Chem. 1999, 111, 2333 – 2335; Angew. Chem. Int. Ed.
1999, 38, 2196 – 2199; for related effects see: c) K. Mikami, T.
Korenaga, M. Terada, T. Ohkuma, T. Pham, R. Noyori, Angew.
Chem. 1999, 111, 517 – 519; Angew. Chem. Int. Ed. 1999, 38, 495 –
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Rev. 2003, 103, 3345 – 3367; f) P. J. Walsh, A. E. Lurain, J.
Balsells, Chem. Rev. 2003, 103, 3297 – 3344; g) K. Mikami, M.
Yamanaka, Chem. Rev. 2003, 103, 3369 – 3400; h) M. Diꢃguez, O.
Pꢄmies, A. Ruiz, S. Castillꢅn, C. Claver, Chem. Eur. J. 2001, 7,
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Angew. Chem. 2002, 114, 4714 – 4717; Angew. Chem. Int. Ed.
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Received: November 15, 2004
Published online: April 12, 2005
Keywords: asymmetric catalysis · combinatorial catalysis ·
hydrogenation · P ligands · rhodium
.
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Communications
Kameda, K. Maruoka, Angew. Chem. 2002, 114, 1621 – 1624;
Angew. Chem. Int. Ed. 2002, 41, 1551 – 1554; l) C. Monti, C.
Gennari, U. Piarulli, Tetrahedron Lett. 2004, 45, 6859 – 6862;
m) H. Horibe, K. Kazuta, M. Kotoku, K. Kondo, H. Okuno, Y.
Murakami, T. Aoyama, Synlett 2003, 2047 – 2051; n) K. Tissot-
Croset, D. Polet, A. Alexakis, Angew. Chem. 2004, 116, 2480 –
2482; Angew. Chem. Int. Ed. 2004, 43, 2426 – 2428, and
references therein.
[11] Along these lines the use of mixtures of BINOL-derived
phosphoramidites 1 (X = NR2) and fluxional atropisomeric
phosphoramidites (which we have prepared from biphenol and
amines such as dimethylamine and piperidine) offers interesting
perspectives.
[12] For more work on combinatorial catalysis see: M. T. Reetz, X.
Li, Angew. Chem. 2005, 117, 3022–3024; Angew. Chem. Int. Ed.
2005, 44, 2962–2964.
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