Chiral Monophosphites and Monophosphonites as Ligands in Asymmetric Transition Metal Catalysis

Article abstract of DOI:10.1023/A:1025545831942

Chiral monophosphites and monophosphonites derived from BINOL are more effective ligands in enantioselective rhodium-catalyzed hydrogenation of olefins, as compared to bidentate bis-phosphites. An appreciable increase in enantioselectivity is attained with the use of mixtures of two different monodentate phosphites and phosphonites in rhodium-catalyzed hydrogentation.

Full text of DOI:10.1023/A:1025545831942

Russian Journal of Organic Chemistry, Vol. 39, No. 3, 2003, pp. 392 396. From Zhurnal Organicheskoi Khimii, Vol. 39, No. 3, 2003, pp. 422 426.
Original English Text Copyright 2003 by Reetz.
Dedicated to Full Member of the Russian Academy of Sciences
I.P. Beletskaya on Her Jubilee
Chiral Monophosphites and Monophosphonites as Ligands
in Asymmetric Transition Metal Catalysis*
M. T. Reetz
Max-Planck-Institut fur Kohlenforschung, Kaiser-Wilhelm-Platz 1, D-45470, Mulheim/Ruhr, Germany
Received November 30, 2002
Abstract Chiral monophosphites and monophosphonites derived from BINOL are more effective ligands
in enantioselective rhodium-catalyzed hydrogenation of olefins, as compared to bidentate bis-phosphites.
An appreciable increase in enantioselectivity is attained with the use of mixtures of two different monodentate
phosphites and phosphonites in rhodium-catalyzed hydrogentation.
Asymmetric transition metal catalysis is of con-
siderable academic and industrial interest [1], as
evidenced by the award of the Nobel Prize for
Chemistry 2001 to K.B. Sharpless [2], R. Noyori [3],
and W.S. Knowles [4]. Many practical, mechanistic,
and theoretical advances have been made. One of the
long-standing dogmas of asymmetric hydrogenation
is the postulate that chelating bidentate ligands (such
as chiral diphosphines) are necessary in order to
achieve high levels of enantioselectivity (ee > 90%)
[1, 3, 4].
are better and even cheaper ligands for Rh-catalyzed
hydrogenation [6]. Simple alcohols II were used as
building blocks in the modular synthesis of a number
of chiral monophosphites. Scheme 1 shows only a few
selected examples, as well as the result of using these
simple ligands in the Rh-catalyzed hydrogenation of
itaconic acid ester (IV). In the original publication
[6], a ligand-to-Rh ratio of only 1:1 was used, but in
fact 2:1 is more efficient (the ee values differ only
slightly). As can be seen, the ee values range between
35% and 97.8%, depending upon the nature of alcohol
II which is used in the synthesis of the ligand.
As a part of our study of chiral BINOL-derived
bidentate bis-phosphites [5], we made an unexpected
discovery, namely that analogous monophosphites III
Moreover, a variety of 2-acetamido acrylic acid
esters were hydrogenated in a similar way with high
Scheme 1.
III, R = Me (ee 83.4%) (a), Et (93.4%) (b), cyclo-C6H11 (96.8%) (c), t-Bu (91.4%) (d), Ph (97.8%) (e), 2,6-Me2C6H3 (35.0%) (f),
i-Pr (97.0%) (g), 9-fluorenyl (96.0%) (h).
____________
*
The original article was submitted in English.
1070-4280/03/3903-0392$25.00 2003 MAIK Nauka/Interperiodica

CHIRAL MONOPHOSPHITES AND MONOPHOSPHONITES AS LIGANDS
393
degree of enantioselectivity, as in the case of the
parent substrate shown in Scheme 2 [6]. Rhodium-to-
substrate ratios of 1:1000 and even 1:5000 can be
used in these reactions at room temperature (hydrogen
pressure 1.3 atm). The conversion is usually complete.
BINOL-derived monophosphonites XI are also
interesting ligands, although they are generally less
efficient (they exhibit higher activity but ensure
slightly lower enantioselectivity).
These developments show that the long-standing
dogma [1, 3, 4] that chelating (bidentate) ligands are
necessary in order to observe high enantioselectivities
in hydrogenation no longer pertains. However, the
source of high enantioselectivity has not yet been
fully illuminated. We have examined the NMR spectra
of precatalysts Rh(L2*(COD)BF4 and have proven that
two chiral monophosphites (L*) are bonded to
rhodium. Moreover, strong nonlinear effects are ob-
served (see figure), suggesting that two monophos-
phites are attached to the metal in the transition state
of hydrogenation and/or in a preequilibrium step [12].
Preliminary kinetic studies showed the following
order in the rate of Rh-catalyzed hydrogenation:
monophosphonites > monophosphites > monophos-
phoramidites. In the case of monophosphites turnover
numbers of 200000 have been achieved.
Scheme 2.
Ligand IIIa, ee 76.6%; IIIb, 83.6%; IIIc, 94.6%; IIId,
95.4%; IIIe, 78.6%; IIIf, 32.4%; IIIg, 94.4%; IIIh, 92.4%.
These mechanistic advances show that probably
two phosphites are bonded to rhodium (as do NMR
experiments), but they do not explain the source of
enantioselectivity on a molecular basis. Thus, further
studies are necessary before final conclusions can be
reached. We have not been able to obtain adequate
crystals of relevant Rh complexes. However, the
X-ray crystal structure of the first metal complex of
a BINOL-derived phosphorous acid ester was recently
analyzed in our laboratories [13]. It is a Pt complex
in which the acidic OH functions are H-bonded to
triethylamine. The structure has cis arrangement of
the two chiral ligands (Scheme 3). It is currently
unclear to what extent rotation about the Pt P bond
is reduced or inhibited in complexes of this type,
which may bear some resemblance to Rh complexes
Finally, industrially important chiral amines IX
can also be prepared with high enantioselectivity from
N-acyl enamines VIII [7]. The optimized ee values
range from 90% to 98%, depending on the nature of
the alcohol component in the chiral monophosphite.
These results demonstrate once more the power of
the modular nature of these readily accessible ligands.
Moreover, the ligands are cheap (only 2% of the cost
of BINAP), which makes them very attractive for
industrial applications [8].
R = aryl; R = H, Me.
Independently, Feringa and co-workers have shown
that phosphoramidite X is also an excellent ligand in
Rh-catalyzed hydrogenation of olefins [9]. Moreover,
Pringle [10] and we [11] have reported that analogous
Nonlinear effects in the Rh-catalyzed hydrogenation of
itaconic acid ester IV using monophosphite IIIg derived
from BINOL and 2-propanol [12].
XI, R = Me (a), Et (b), cyclo-C6H11 (c), t-Bu (d), Ph (e), Cl (f).
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 39 No. 3 2003

394
REETZ
Scheme 3.
used in hydrogenation. If restricted rotation around
the P metal bonds pertains, then the two mono-P-
units simulate a chelating bidentate ligand system,
a phenomenon which would explain high enantio-
selectivity in Rh-catalyzed hydrogenation.
chosen as test reaction [14]. Initially, the Rh:La :Lb
ratio was kept constant at 1:1:1. Although not all of
the theoretically possible combinations of La/Lb were
tested, the results summarized in table uncover some
remarkable trends, which need to be compared to the
most enantioselective homo-combinations.
Most recently, we have made an unusual discovery
concerning the use of mixtures of two different
BINOL-derived monophosphites III, two different
monophosphonites XI, or a mixture of III and XI
[14]. It involves a new concept in the area of com-
binatorial enantioselective transition metal catalysis.
The basic idea concerns the use of mixtures of chiral
monodentate ligands. The method is relevant when-
ever in the transition state of the reaction at least
two monodentate ligands (L) are coordinated to the
metal (M) of the active catalyst MLx. For example, in
the case of a mixture of two such ligands La and Lb,
three different catalysts exist in equilibrium with one
another, namely two homo-combinations MLaLa and
MLbLb, as well as hetero-combination MLaLb. Many
examples of homo-combinations are known in the
literature, as in the chemistry described above. In
contrast, nothing has been published concerning the
use of hetero-combinations MLaLb as catalysts. Since
rapid ligand exchange is likely to occur in most
systems, preparation of MLaLb in pure form in solu-
tion is not expected to be possible. However, a mix-
ture of all three catalysts may well lead to enhanced
enantioselectivity provided that MLaLb is more active
and more selective than either of traditional catalysts
MLaLa or MLbLb. It can also be expected that the
relative amounts of the ligands La and Lb used may
influence the stereochemical outcome.
The results show that certain ligand combinations
La/Lb lead to notably high enantioselectivities. In
the case of two different phosphonites (see table,
nos. 15 19), the enantioselectivity is nearly complete
(ee = 98%), when one component bears a small sub-
stituent R at the phosphorus atom (e.g., methyl group,
as in XIa) and the other is bulky (nos. 16 and 17).
The results show significant improvements relative to
the corresponding homo-combinations which lead to
ee values of only 92 94% (nos. 1, 3, 4). Acceptable
ee values are obtained in the phosphite series (nos.
21 36), but in most cases improvements upon using
hetero-combinations are limited. The greatest effect
is observed in going from homo-combinations IIIa
(ee = 76.6%) and IIIf (ee = 32.4%) to the hetero-
combination based on the same ligands, IIIa/IIIf
(ee = 84.6%) (no. 25). In contrast, the use of proper
combinations of phosphonites XI and phosphites III
gives pronounced enhancements in enantioselectivity,
especially if a bulky phosphonite (e.g., XIc or XId)
is combined with the least sterically demanding phos-
phite IIIa (nos. 40 and 42), as in the case of XII:
The Rh-catalyzed hydrogenation of acetamido-
acrylic acid ester VI in methylene chloride was
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 39 No. 3 2003

CHIRAL MONOPHOSPHITES AND MONOPHOSPHONITES AS LIGANDS
395
Rhodium-catalyzed hydrogenation of methyl 2-acetylamino-2-propenoate (VI) [14]a
Run no.
Ligands
ee, % (configuration)
Run no.
Ligands
ee, % (configuration)
Homo-combinations
1
2
3
4
(R)-XIa/(R)-XIa
(R)-XIb/(R)-XIb
(R)-XIc/(R)-XIc
(R)-XId/(R)-XId
(R)-XIe/(R)-XIe
(R)-XIf/(R)-XIf
(S)-IIIa/(S)-IIIa
91.8 (S)
8
9
(S)-IIIb/(S)-IIIb
(S)-IIIc/(S)-IIIc
(S)-IIId/(S)-IIId
(S)-IIIe/(S)-IIIe
(S)-IIIf/(S)-IIIf
(S)-IIId/(S)-IIId
(S)-IIIh/(S)-IIIh
83.6 (R)
94.6 (S)
95.4 (R)
78.6 (R)
32.4 (R)
94.4 (R)
92.4 (R)
94.4 (S)
92.0 (S)
93.3 (S)
72.8 (S)
7.4 (S)
10
11c
12d
13
14
5
6b
7
76.6 (R)
Hetero-combinations
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
(R)-XIa/(R)-XIb
(R)-XIa/(R)-XIc
(R)-XIa/(R)-XId
(R)-XIc/(R)-XId
(R)-XId/(R)-XIe
(R)-XId/(R)-XIf
(R)-IIIa/(R)-IIIb
(R)-IIIa/(R)-IIIc
(R)-IIIa/(R)-IIId
(R)-IIIa/(R)-IIIe
(R)-IIIa/(R)-IIIf
(R)-IIIa/(R)-IIId
(R)-IIIb/(R)-IIIc
(R)-IIIb/(R)-IIId
(R)-IIIb/(R)-IIIe
(R)-IIIb/(R)-IIIf
92.6 (S)
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
(R)-IIId/(R)-IIIc
(R)-IIId/(R)-IIIe
(R)-IIIe/(R)-IIIc
(R)-IIId/(R)-IIIc
(R)-IIId/(R)-IIId
(R)-IIId/(R)-IIIe
(R)-XIa/(R)-IIIa
(R)-XIa/(R)-IIIc
(R)-XIa/(R)-IIId
(R)-XIc/(R)-IIIa
(R)-XIc/(R)-IIId
(R)-XId/(R)-IIIa
(R)-XId/(R)-IIIc
(R)-XId/(R)-IIIh
(R)-XIc/(R)-IIIh
94.2 (S)
92.2 (S)
73.6 (S)
94.6 (S)
94.8 (S)
91.2 (S)
81.9 (S)
94.4 (S)
93.0 (S)
96.4 (S)
91.8 (S)
98.0 (S)
94.6 (S)
97.2 (S)
95.6 (S)
97.9 (S)
97.8 (S)
94.1 (S)
75.8 (S)
Racemate
80.0 (S)
76.6 (S)
89.0 (S)
77.4 (S)
84.6 (S)
87.2 (S)
79.0 (S)
91.2 (S)
80.8 (S)
90.0 (S)
a
Rh-to-substrate ratio 1:1000; Rh-to-P ratio 1:2; solvent CH2Cl2; hydrogen pressure 1.3 bar; temperature 20 C; reaction time 20 h;
conversion 100%.
Conversion 1%.
Conversion 93%.
Conversion 62%.
b
c
d
Similar results were observed in the hydrogenation
We expect that other reaction types are also amenable
to this type of combinatorial optimization. Moreover,
mixtures of achiral mono-P-ligands in achiral trans-
formations may also be worthy of study.
of substituted derivatives of VI, itaconic acid dimethyl
ester (IV), and N-acyl enamines VIII [14]. Thus,
a new principle has been established in combinatorial
asymmetric catalysis [15].
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monophosphites and monophosphonites, especially
those derived from readily available BINOL, are
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