Binol-derived monodentate phosphites and phosphoramidites with phosphorus stereogenic centers: Novel ligands for transition-metal catalysis

Article abstract of DOI:10.1002/anie.200461624

(Chemical Equation Presented) Buried in the symmetry: Phosphorylation of ortho-substituted binol derivatives leads to monodentate phosphites (X = OR) or phosphoramidites (X = NR₂) having stereogenic centers at phosphorus (see scheme). Such compounds are excellent ligands in rhodium-catalyzed olefin-hydrogenation (95-99% ee) surpassing the C₂-symmetric parent ligands.

Full text of DOI:10.1002/anie.200461624

Communications
Asymmetric Catalysis
Binol-Derived Monodentate Phosphites and
Phosphoramidites with Phosphorus Stereogenic
Centers: Novel Ligands for Transition-Metal
Catalysis**
Manfred T. Reetz,* Jun-An Ma, and Richard Goddard
Recently three groups independently reported that binol-
derived monodentate phosphites 1a,[1] phosphonites 1b,[2] and
phosphoramidites 1c[3] are efficient ligands in rhodium-
catalyzed asymmetric olefin hydrogenation (ee values = 90–
99%; binol = 2,2’-dihydroxy-1,1’-binaphthyl). A preliminary
[*] Prof. Dr. M. T. Reetz, Prof. Dr. J.-A. Ma, Dr. R. Goddard
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
[**] Binol=2,2’-dihydroxy-1,1’-binaphthyl.
412
ꢀ 2005 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
DOI: 10.1002/anie.200461624
Angew. Chem. Int. Ed. 2005, 44, 412 –415

Angewandte
Chemie
mechanistic study by our group shows that
two monodentate phosphorus compounds are
bonded to rhodium in the hydrogenation
transition state. In an extension of this work
we demonstrated that mixtures of two differ-
ent monodentate phosphorus ligands can be
used in a combinatorial approach.[4] Since
binol is one of the cheapest chiral auxiliaries
currently available, chemical modification
resulting in the formation of new modular
ligands appears attractive.
We wondered whether binol derivatives
bearing a single ortho-substituent as in (S)-2
(Scheme 1) can serve as starting materials for
structurally unusual monodentate phospho-
rus ligands. This modification would not only
reduce C2 to C1 symmetry, it would also lead
Scheme 2. Synthesis of phosphoramidites 6 and 7 and phosphite 8. a) 1. RX/base, 2. CH3OH/HCl;
b) P(NMe2)3/toluene, 1108C, 1–2 h; c) 1. PCl3/Et3N, Et2O, ꢀ78!08C, 2. piperidine/Et3N, Et2O, RT,
24 h; d) 1. PCl3/Et3N, Et2O, ꢀ78!08C, 2. iPrOH/Et3N, Et2O, RT, 24 h.
to the creation of a stereogenic center at phosphorus (RP and
SP in diastereomers 3; Scheme 1).[5] Herein we report the
synthesis of this novel class of phosphorus ligands and their
use in rhodium-catalyzed olefin hydrogenation.
then made on the basis of an X-ray structural analysis of the
major diastereomer of 6a, which has the S,SP configuration,[7]
and in other cases by comparison of 31P NMR spectroscopy
data. In the 31P NMR spectrum the signal of the S,Sp ligands
appears at higher d values than that of the S,RP diastereomers,
a conclusion that was corroborated by the X-ray data of
another derivative (see below). Subsequently, the first
rhodium-catalyzed hydrogenations were performed with
olefins 9 and 11 (Scheme 3).
Scheme 1. Formation of diastereomeric ligands with stereogenic phos-
phorus centers.
Starting from the known methoxymethyl (MOM) pro-
tected (S)-binol-derivative 4,[6] compounds 5a–c were readily
prepared which were then treated with P(NMe2)3 in boiling
toluene. This reaction resulted in excellent yields of the
phosphoramidites as diastereomeric mixtures or as pure
compounds: 6a (S,SP:S,RP = 2:1), 6b (S,SP pure), and 6c
(S,SP:S,RP = 10:1; Scheme 2). Reaction of 5a–c with PCl3/
NEt3 at ꢀ788C followed by treatment with piperidine
provided phosphoramidites 7 (Scheme 2), the S,RP com-
pounds being the major diastereomers in these cases. The
formation of the major diastereomers appears to be kineti-
cally controlled under these conditions, because heating
compound 7a at 1108C for 48 h changed the diastereomeric
ratio S,RP:S,SP from 3:1 to 2.3:1. Treatment of compounds 5
with PCl3/NEt3 followed by reaction with an alcohol in the
presence of NEt3 provides the analogous phosphites, for
example phosphite 8 (S,RP:S,SP = 3.8:1; Scheme 2).
Scheme 3. Rhodium-catalyzed hydrogenation of olefins 9 and 11;
cod=cyclooctadiene.
Table 1 reveals that excellent enantioselectivities were
achieved in some but not all cases and that the absolute
configuration of the binol ligand dictates the direction of
enantioselectivity. In the case of the hydrogenation of itaconic
acid dimethyl ester (9) using ligand 6a the configuration at
the phosphorus center also plays a significant role. The pure
S,SP ligand leads to an ee value of 96.3% (S; Table 1, entry 1),
whereas the pure S,RP diastereomer is less efficient (ee =
72.5% S, entry 4). Thus, the S,SP diastereomer represents
the matched case. The mixtures of diastereomeric ligands give
rise to intermediate ee values (entries 2 and 3). These
Some of the diastereomers were separated by crystalliza-
tion, others by HPLC. The configuration assignments were
Angew. Chem. Int. Ed. 2005, 44, 412 –415
www.angewandte.org
ꢀ 2005 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
413

Communications
tion.[7] The precatalyst [Rh(14e)2(cod)]BF4 was also charac-
terized by X-ray crystallography (Figure 1).[9] The metal
cation has an almost ideal twofold axis of symmetry despite
a highly unsymmetrical crystal environment caused by the
Table 1: Rhodium-catalyzed hydrogenation of olefins 9 and 11 by using
ligands 6, 7, and 8.[a]
Entry Olefin Ligand
Major enantiomer ee [%]
of 10 or 12
1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
16
17
18
19
20
9
9
9
9
9
9
9
9
9
9
6a (S,SP pure)
S
S
S
S
S
S
S
S
S
S
R
R
R
R
R
R
R
R
R
R
96.3
93.0
90.5
72.5
95.4
96.1
96.0
96.3
96.8
91.3
99.0
98.7
98.7
97.8
98.3
98.4
>99.0
93.8
98.8
97.0
6a (S,SP:S,RP =2:1)
6a (S,SP:S,RP =1:2.3)
6a (S,RP pure)
6b (S,SP pure)
6c (S,SP:S,RP =10:1)
7a (S,SP:S,RP =1:3)
7b (S,SP:S,RP =1:1.4)
7c (S,SP:S,RP =1:2.2)
8 (S,SP:S,RP =1:3.8)
11 6a (S,SP pure)
11 6a (S,SP:S,RP =2:1)
11 6a (S,SP:S,RP =1:2.3)
11 6a (S,RP pure)
11 6b (S,SP pure)
11 6c (S,SP:S,RP =10:1)
11 7a (S,SP:S,RP =1:3)
11 7b (S,SP:S,RP =1:1.4)
11 7c (S,SP:S,RP =1:2.2)
11 8 (S,SP:S,RP =1:3.8)
Figure 1. Structure of the cation of [Rh{(S,SP)-14e}2(cod)]BF4 showing
the almost exact twofold axis of symmetry passing through the Rh
atom (arrow). Selected interatomic distances [ꢁ], angles, and torsion
angles [8]: Rh-P1 2.277(1), Rh-P2 2.275(1), P1-N1 1.640(2), P2-N2
1.633(3), C39···Rh 3.381(3), C79···Rh 3.377(3), P1-Rh-P2 94.89(2), C39-
N1-P1-Rh 5(1), C79-N2-P2-Rh 3(1).[9]
[a] All reactions in CH2Cl2; Rh:L=1:2; Rh:olefin=1:200; 1.3 bar; 20 h;
100% conversion in all cases.
[BF4]ꢀ ion and CH2Cl2 solute of crystallization. This situation
suggests that crystal-packing effects are not the cause of the
high symmetry. An electron-donating effect of nitrogen onto
phosphorus which is passed onto the positively charged
mixtures constitute a more complex case because, as the
rhodium center is coordinated by two binol ligands, three
catalysts are actually involved, namely Rh(S,SP/S,SP),
Rh(S,RP/S,RP), and Rh(S,SP/S,RP), each is present in a differ-
ent amount and reacts with a different rate. Table 1 shows that
with 9, in five cases the ee values exceed 96%, which is
distinctly better than the 87% ee resulting from the use of the
parent C2-symmetric phosphoramidite 1c (R = CH3).[3a] The
mixture of diastereomeric phosphites 8 leads to a respectable
91.3% ee (entry 10), but at present we do not know how the
pure diastereomers perform. In the hydrogenation of olefin
11, ligand 6a (S,SP pure) also constitutes the matched case, but
the cooperative effect is not as pronounced (entry 11 versus
14).
rhodium center seems to be operating. Another feature is a
+
ꢀ
weak C H···Rh interaction between one of the H atoms of a
methyl group in the planar N(CH3)2 moiety and the metal.[10]
Although the rhodium complexes of the other ligands which
have less-bulky ortho-substituents could not be crystallized to
date, they may have similar structures.
Upon employing the ligands 14 in the rhodium-catalyzed
hydrogenation of olefins 9 and 11, some remarkable obser-
vations were made (Table 2). The methyl derivative 14a
behaves much like the ligands 6, 7, and 8, affecting S selec-
tivity (91% ee, entry 1). In contrast, upon using the phenyl
derivative 14b, we were surprised to observe R selectivity
(entries 2–5). This effect is opposite to what occurs when
using the C2-symmetric parent compounds (S)-1 which also
originates from (S)-binol; all of the parent ligands are known
to be S-selective in the hydrogenation of 9 (1a (R = iPr):
89.2% ee;[1] 1b (X = CH3): 90% ee;[2] 1c (R = CH3):
87% ee).[3a] Reversal of enantioselectivity on using ligand
14b occurs both in the matched case S,RP with 70% ee
(entry 5) and in the non-cooperative combination S,SP
(20.6% ee, entry 2). This result means that breaking the
symmetry of the ligands from C2 to C1 by introduction of an
ortho-phenyl group induces a reversal of enantioselectivity
which is independent of the configuration at the stereogenic
phosphorus center. We also note that mixtures of diaster-
eomers 14b result in distinctly higher enantioselectivities than
the use of the respective pure ligands themselves, ee values up
to 90.3% being achieved (entries 3 and 4). The use of two
diastereomers constitutes a novel extension of our concept of
employing mixtures of two different monodentate ligands[4]
We phosphorylated the known (S)-binol derivatives 13[8]
which resulted in formation of phosphoramidites 14a–e, and
in two cases proceeded with complete diastereoselectivity
(Scheme 4).
The X-ray structural analysis of the triphenylsilyl-deriv-
ative 14e shows the free ligand to have the S,SP configura-
Scheme 4. Synthesis of phosphoramidites 14.
414
ꢀ 2005 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.angewandte.org
Angew. Chem. Int. Ed. 2005, 44, 412 –415

Angewandte
Chemie
b) M. T. Reetz, G. Mehler, Tetrahedron Lett. 2003, 44, 4593 –
Table 2: Rhodium-catalyzed hydrogenation of olefins 9 and 11 using
ligands 14.[a]
4596; c) M. T. Reetz, G. Mehler, A. Meiswinkel, Tetrahedron:
Asymmetry 2004, 15, 2165 – 2167; see also: d) D. Peꢀa, A. J.
Minnaard, J. A. F. Boogers, A. H. M. de Vries, J. G. de Vries,
B. L. Feringa, Org. Biomol. Chem. 2003, 1, 1087 – 1089; e) A.
Duursma, R. Hoen, J. Schuppan, R. Hulst, A. J. Minnaard, B. L.
Feringa, Org. Lett. 2003, 5, 3111 – 3113.
Entry Olefin Ligand
Major enantiomer ee [%]
of 10 or 12
1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
16
9
9
9
9
9
9
9
9
9
9
14a (S,SP:S,RP =7.8:1)
14b (S,SP pure)
14b (S,SP:S,RP =1:1)
14b (S,SP:S,RP =1:6)
14b (S,RP pure)
S
91.0
20.6
90.3
79.6
70.0
23.0
0
R
R
R
R
S
rac
R
R
R
R
S
[5] Recent examples of P ligands with stereogenic centers at
phosphorus for catalysis: a) W. Tang, X. Zhang, Chem. Rev.
2003, 103, 3029 – 3069; b) K. V. L. Crꢁpy, T. Imamoto, Adv.
Synth. Catal. 2003, 345, 79 – 101; c) P.-H. Leung, Acc. Chem. Res.
2004, 37, 169 – 177; d) W. Tang, W. Wang, Y. Chi, X. Zhang,
Angew. Chem. 2003, 115, 3633 – 3635; Angew. Chem. Int. Ed.
2003, 42, 3509 – 3511; e) G. Hoge, J. Am. Chem. Soc. 2003, 125,
10219 – 10227; f) T. Imamoto, V. L. Crꢁpy, K. Katagiri, Tetrahe-
dron: Asymmetry 2004, 15, 2213 – 2218.
[6] S. Matsunaga, J. Das, J. Roels, E. M. Vogl, N. Yamamoto, T. Iida,
K. Yamaguchi, M. Shibasaki, J. Am. Chem. Soc. 2000, 122, 2252 –
2260.
[7] The geometry of the phosphoramidito ligands is almost identical
in the crystal structures of the (S,SP)-3-benzoyloxymethyl-
derivative 6a and the (S,SP)-3-triphenylsilyl-derivative 14e.[9b]
[8] P. J. Cox, W. Wang, V. Snieckus, Tetrahedron Lett. 1992, 33,
2253 – 2256.
14c (S,SP:S,RP =1:1)
14d (S,SP pure)
14d (S,SP pure)[b]
14e (S,SP pure)
31.6
3.4
14e (S,SP pure)[b]
17.0
98.0
33.6
50.6
97.2
87.2
34.0
11 14a (S,SP:S,RP =7.8:1)
11 14b (S,SP pure)
11 14b (S,RP pure)
11 14c (S,SP:S,RP =1:1)
11 14d (S,SP pure)
11 14e (S,SP pure)
R
R
R
R
[a] Same conditions as in Table 1; 100% conversion. [b] In this case a
ligand:Rh ratio of 1:1 was chosen.
[9] a) Crystal
data
for
[{(S,Sp)-14e}2Rh(cod)]+[BF4]ꢀ
·CH2Cl2:[C88H76N2O4P2RhSi2]+[BF4]ꢀ·CH2Cl2, crystals grown
from dichloromethane/ethyl acetate/diethyl ether/pentane,
Mr = 1618.27, crystal size: 0.04 ꢂ 0.08 ꢂ 0.18 mm3; a = 9.9676(1),
b = 24.3928(1), c = 31.6031(2) ꢃ, V= 7683.9(1) ꢃ3, T= 100 K,
and raises fundamental theoretical questions. The fact that
the triphenylsilyl-derivative 14e is a poor ligand for catalysis
can be rationalized on the basis of the crystal structure of
[Rh{(S,SP)-14e}2(cod)]BF4 (Figure 1). The silyl groups are so
bulky that hydrogenation may actually be inhibited; the
rhodium complex with only one phosphoramide ligand may
function as the actual (pre)catalyst.
In summary, we have prepared and characterized a new
class of binol-derived monodentate phosphorus ligands bear-
ing phosphorus stereogenic centers. They are excellent
ligands in rhodium-catalyzed olefin hydrogenation, a result
which raises important mechanistic questions. On the prac-
tical side, this new class of modular phosphorus compounds
enlarges the structural diversity of binol-derived monoden-
tate phosphorus ligands, which means that they are also
candidates for our combinatorial approach using mixtures[4]
of chiral monodentate phosphorus ligands in hydrogenation
and in other transition-metal-catalyzed reactions.
orthorhombic, space group P212121 (No. 19), Z = 4, 1calcd
1.399 gcmꢀ3, F(000) = 3344, Nonius KappaCCD diffractometer,
l(MoKa) = 0.71073 ꢃ, m = 0.429 mmꢀ1
75490 measured and
=
,
18928 independent reflections (Rint = 0.056), 17187 with I >
2s(I), qmax = 28.288, Tmin = 0.968, Tmax = 0.996, direct methods
(SHELXS-97) and least-squares refinement (SHELXL-97) on
F2o, both programs from G. Sheldrick, University of Gꢄttingen,
1997; 964 parameters, Flack parameter ꢀ0.03(1), H atoms riding,
Chebyshev weights, R1 = 0.0392 (I > 2s(I)), wR2 = 0.0898 (all
data), D1max/min = 0.868/ꢀ0.624 eꢃꢀ3. b) CCDC-247341, CCDC-
247342, CCDC-247343 contain the supplementary crystallo-
graphic data for this paper. These data can be obtained free of
charge via www.ccdc.cam.ac.uk/conts/retrieving.html (or from
the Cambridge Crystallographic Data Centre, 12 Union Road,
Cambridge CB21EZ, UK; fax: (+ 44)1223-336-033; or deposit@
ccdc.cam.ac.uk).
[10] Examples of crystal structure of other rhodium phosphoramidite
complexes: a) A.-G. Hu, Y. Fu, J.-H. Xie, H. Zhou, L.-X. Wang,
Q.-L. Zhou, Angew. Chem. 2002, 114, 2454 – 2456; Angew.
Chem. Int. Ed. 2002, 41, 2348 – 2350; b) M. van den Berg, A. J.
Minnaard, R. M. Haak, M. Leeman, E. P. Schudde, A. Meetsma,
B. L. Feringa, A. H. M. de Vries, C. E. P. Maljaars, C. E. Willans,
D. Hyett, J. A. F. Boogers, H. J. W. Henderickx, J. G. de Vries,
Adv. Synth. Catal. 2003, 345, 308 – 323.
Received: August 12, 2004
Keywords: asymmetric catalysis · hydrogenation · P ligands ·
.
phosphites · rhodium
[1] a) M. T. Reetz, G. Mehler, Angew. Chem. 2000, 112, 4047 – 4049;
Angew. Chem. Int. Ed. 2000, 39, 3889 – 3890; b) M. T. Reetz,
Chim. Oggi 2003, 21(10/11), 5 – 8.
[2] a) M. T. Reetz, T. Sell, Tetrahedron Lett. 2000, 41, 6333 – 6336;
b) C. Claver, E. Fernandez, A. Gillon, K. Heslop, D. J. Hyett, A.
Martorell, A. G. Orpen, P. G. Pringle, Chem. Commun. 2000,
961 – 962.
[3] a) M. van den Berg, A. J. Minnaard, E. P. Schudde, J. van Esch,
A. H. M. de Vries, J. G. de Vries, B. L. Feringa, J. Am. Chem.
Soc. 2000, 122, 11539 – 11540; b) D. Peꢀa, A. J. Minnaard,
A. H. M. de Vries, J. G. de Vries, B. L. Feringa, Org. Lett. 2003,
5, 475 – 478.
[4] a) M. T. Reetz, T. Sell, A. Meiswinkel, G. Mehler, Angew. Chem.
2003, 115, 814 – 817; Angew. Chem. Int. Ed. 2003, 42, 790 – 793;
Angew. Chem. Int. Ed. 2005, 44, 412 –415
www.angewandte.org
ꢀ 2005 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
415