A kinetic study on Rh/binap-catalyzed 1,4-addition of phenylboronic acid to enones: Negative nonlinear effect caused by predominant homochiral dimer contribution

Article abstract of DOI:10.1021/ja060225v

A kinetic study on the Rh/binap-catalyzed 1,4-addition of phenylboronic acid using reaction calorimetry revealed that the catalytically inactive dimeric hydroxorhodium complex [Rh(OH)((R)-binap)]₂ (RR-4) is the resting state. A negative NLE in ee_prod and an amplified reaction rate were predicted and observed in the present reaction system characterized by the preferential formation of homochiral dimer. Copyright

Full text of DOI:10.1021/ja060225v

Published on Web 03/08/2006
A Kinetic Study on Rh/Binap-Catalyzed 1,4-Addition of Phenylboronic Acid to
Enones: Negative Nonlinear Effect Caused by Predominant Homochiral
Dimer Contribution
Asato Kina,† Hiroshi Iwamura,‡ and Tamio Hayashi*,†
Department of Chemistry, Graduate School of Science, Kyoto UniVersity, Sakyo, Kyoto 606-8502, Japan, and
Mitsubishi Pharma Corporation, Kamisu, Ibaraki 314-0255, Japan
Received January 11, 2006; E-mail: thayashi@kuchem.kyoto-u.ac.jp
The 1,4-addition of organometallic reagents to R,â-unsaturated
compounds is a widely used process for carbon-carbon bond
formation.1 Chiral catalytic system for the 1,4-addition of aryl and
alkenylboronic acids has been developed by use of a Rh/binap
catalyst.2,3 Although its catalytic cycle has been proposed on the
basis of NMR studies of the intermediates,4 its kinetic understanding
has not been afforded due to the difficulty of analysis of the
multistep catalytic reaction.5 Recently, Blackmond developed the
methodology of reaction progress kinetic analysis utilizing reaction
calorimetry and provided a powerful tool for kinetic analysis on
complicated catalytic reactions including transition-metal-catalyzed
reactions.6 Here we report a detailed kinetic study of Rh/binap-
catalyzed 1,4-addition of phenylboronic acid to R,â-unsaturated
ketones. An inactive dimeric hydroxorhodium complex is found
to be a dominant species in the catalytic cycle, which was confirmed
by quantitative investigation of the nonlinear effect.
Figure 1. Rate vs [1] and rate/[Rh]t0.5 vs [1] (inset) for the reactions of 1
with 2 in 1,4-dioxane (3.0 mL) and H2O (0.3 mL) in the presence of
[B(OH)3]0 ) 260 mM at 50 °C. The progress of the reaction runs from
right to left in these figures. The data during the first 3 min were omitted
for the clarify. The solid lines represent the kinetic model given in eq 2.
Reaction conditions: (a) [1]0 ) 71.7 mM, [2]0 ) 194 mM, [RR-4] ) 8.00
mM Rh; (b) [1]0 ) 128 mM, [2]0 ) 248 mM, [RR-4] ) 8.00 mM Rh; (c)
[1]0 ) 69.7 mM, [2]0 ) 124 mM, [RR-4] ) 8.00 mM Rh; (d) [1]0 ) 88.7
mM, [2]0 ) 197 mM, [RR-4] ) 8.00 mM Rh; (e) [1]0 ) 66.0 mM, [2]0 )
184 mM, [RR-4] ) 16.0 mM Rh.
Scheme 1
Scheme 2. Reaction Network of Rh/Binap-Catalyzed 1,4-Addition
of Phenylboronic Acid (1) to Methyl Vinyl Ketone (2)
The reactions between phenylboronic acid (PhB(OH)2, 1)7 and
an excess amount of methyl vinyl ketone (MVK, 2)8 in aqueous
1,4-dioxane in the presence of [Rh(OH)((R)-binap)]2 (RR-4) as a
catalyst and boric acid (H3BO3)9 (Scheme 1) were continuously
monitored in a reaction calorimeter (Omnical SuperCRC), and the
kinetic behavior was analyzed by using the method of [“excess”]
relationship and graphical rate equation developed by Black-
mond.10,11 Constant catalyst concentration and steady-state behavior
were confirmed by the results of kinetic profiles for two reactions
at the same [“excess”] overlaid with one another when plotted as
rate versus the concentration of PhB(OH)2 [1] (Figure 1, a and b).
The plot of rate versus [1] is a straight line suggestive of first-
order kinetics, and zero-order kinetics in the concentration of MVK
[2] is confirmed by the reaction employing different [“excess”] (a,
c, and d). It is significant that the reaction rate does not show
proportional increase by the addition of catalyst. Rate divided by
the square root of rhodium concentration (rate/[Rh]total0.5) is plotted
versus PhB(OH)2 concentration [1] to show that the reaction is half-
order in rhodium concentration throughout the entire course of the
reaction (Figure 1, inset, a and e).
forming oxo-π-allylrhodium, and its hydrolysis giving the 1,4-
addition product and hydroxorhodium species. Due to the half-
order kinetics in [Rh]total, this catalytic cycle was modified to involve
an equilibrium between the monomeric species 5 and the dimeric
hydroxorhodium 4, which is characterized by the dimerization
constant Kdimer (Scheme 2).12 The dissociation of the catalytically
inactive dimer 4 forms the active monomeric rhodium 5, which
has a reactive vacant site coordinated weakly with a solvent
molecule. As a kinetic model, we assumed the transmetalation step
characterized by the rate constant k1. The subsequent two steps,
insertion of MVK 2 and hydrolysis forming product 3, were
combined and characterized by the rate constant k2.13 Using the
steady-state treatment for the rhodium species 4, 5, and 6, we wrote
a reaction rate expression (eq 1). The large value for Kdimer, which
is demonstrated by the half-order kinetics in [Rh]total, simplifies eq
1 to eq 2, which is in good agreement with the reaction orders in
substrates and catalyst described above. Excellent fits between
experimental rate data and calculated rate were found when the
Our previous NMR studies have revealed4 that the catalytic cycle
involves transmetalation of phenyl group from boron to hydroxo-
rhodium, addition of the resulting phenylrhodium bond to an enone
† Kyoto University.
‡ Mitsubishi Pharma Corporation.
9
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J. AM. CHEM. SOC. 2006, 128, 3904-3905
10.1021/ja060225v CCC: $33.50 © 2006 American Chemical Society

C O M M U N I C A T I O N S
constant for eq 2 has the value of k1/(2Kdimer
) 0.98).14
)
0.5 ) 12 M-0.5 s-1 (R2
2k1k2[PhB(OH)2(1)][MVK(2)][Rh]total
A + {A2 + 8Kdimer(k2[MVK(2)])2[Rh]total
ν )
0.5
}
A ) k1[PhB(OH)2(1)] + k2 [MVK(2)]
(1)
(2)
k1
0.5
ν )
0.5[PhB(OH)2(1)][Rh]total
(2Kdimer
)
Figure 2. eeprod vs eecat (left) and νee/ν100%ee vs eecat (right). Simulation
(solid lines) and observation (squares) of the nonlinear effect in the reaction
of 1 to 7.
The existence of the dominant dimeric species prompted us to
carry out a quantitative nonlinear effect (NLE) analysis, because
NLE is generally attributed to the formation of diastereomeric
species or higher-order agglomerates.15 31P NMR of the racemic
binap-hydroxorhodium complex (10 mM in 1,4-dioxane/H2O (10/
1) at 29 °C) showed only one doublet at δ 54.9 Hz (JP-Rh ) 185
Hz), which is the same as that of enantiopure binap-hydroxo-
rhodium complex, indicating that the homochiral dimer is over-
whelmingly more stable than the heterochiral dimer. Kitamura and
Noyori described mathematical treatment of NLE in their reports
on asymmetric alkylation of aldehydes with dialkylzinc reagents.16
A negative NLE in eeprod and an amplified reaction rate are expected
in our reaction system characterized by the preferential formation
of homochiral dimer.15,16 Considering that the formation of het-
erochiral dimer RS-9 is negligible, calculation to obtain the
concentrations of monomers [R-5] and [S-5] is very simple, readily
available from the dimerization constant Kdimer obtained for the
homochiral dimer. The equations for eeprod and the reaction rate
(νee) are defined by the concentrations of active monomeric rhodium
complexes [R-5] and [S-5], where ee100%ee (>99% ee) and ν100%ee
are the enantioselectivity and the rate of the reaction by the
enantiopure catalyst, respectively.17
the inactive dimer species RR-4 is the resting state. These results
are consistent with our previous reaction mechanism proposed by
the NMR studies of key intermediates.4
Acknowledgment. This work was partially supported by a
Grant-in-Aid for Scientific Research, the Ministry of Education,
Culture, Sports, Science and Technology, Japan. A.K. thanks the
Japan Society for the Promotion of Science for the award of a
fellowship for graduate students.
Supporting Information Available: Experimental procedures and
detailed kinetic study data. This material is available free of charge
via the Internet at http://pubs.acs.org.
References
(1) A review on 1,4-addition reactions: Perlmutter, P. Conjugate Addition
Reactions in Organic Synthesis; Pergamon Press: Oxford, 1992.
(2) For the first example of Rh-catalyzed asymmetric 1,4-addition of aryl-
and alkenylboronic acids to enones, see: Takaya, Y.; Ogasawara, M.;
Hayashi, T.; Sakai, M.; Miyaura, N. J. Am. Chem. Soc. 1998, 120, 5579.
(3) Reviews: (a) Hayashi, T.; Yamasaki, K. Chem. ReV. 2003, 103, 2829.
(b) Fagnou, K.; Lautens, M. Chem. ReV. 2003, 103, 169. (c) Bolm, C.;
Hildebrand, J. P.; Muniz, K.; Hermanns, N. Angew. Chem., Int. Ed. 2001,
40, 3284. (d) Hayashi, T. Synlett 2001, 879.
(4) Hayashi, T.; Takahashi, M.; Takaya, Y.; Ogasawara, M. J. Am. Chem.
Soc. 2002, 124, 5052.
(5) Helfferich, F. G. Kinetics of Homogeneous Multistep Reactions; Elsevier
Science: Amsterdam, 2001.
νee
[R-5] - [S-5]
[R-5] + [S-5]
[R-5]100%ee
eeprod ) ee
,
)
(3)
100%ee[R-5] + [S-5]
ν100%ee
(6) An expert review: Blackmond, D. G. Angew. Chem., Int. Ed. 2005, 44,
4302.
(7) In the experiments, phenylboroxine ((PhBO)3) was used as a precursor
of phenylboronic acid (1), because the boroxine is easier to be purified.
Arylboroxine and water is in a fast equilibrium with arylboronic acid,
and hence the reaction starting from phenylboronic acid and that starting
from arylboroxine in water should result in the same outcome. Tokunaga,
Y.; Ueno, H.; Shimomura, Y.; Seo, T. Heterocycles 2002, 57, 787.
(8) In the reaction of reactive MVK, hydrolysis of 1 giving benzene as a side
Scheme 3. Nonlinear Effect and Equilibrium Scheme
1
reaction is negligible. H NMR analysis of the reaction mixture showed
<3% formation of benzene.
(9) An excess of boric acid was added to minimize the change of its
concentration throughout the reaction.
(10) The methodology of reaction progress kinetic analysis is described in ref
6 and in the following literature: (a) Rosner, T.; Le Bars, J.; Pfaltz, A.;
Blackmond, D. G. J. Am. Chem. Soc. 2001, 123, 1848. (b) Singh, U. K.;
Strieter, E. R.; Blackmond, D. G.; Buchwald, S. L. J. Am. Soc. Chem.
2002, 124, 14104. (c) Mathew, S. P.; Gunathilagan, S.; Roberts, S. M.;
Blackmond, D. G. Org. Lett. 2005, 7, 4847.
(11) The parameter [“excess”] is defined as the difference in the initial
concentrations of two substrates, [reagent]0 - [substrate]0 to manipulate
the large number of data pairs. The two reactions carried out at the same
[“excess”] reveal unsteady-state influence on kinetic behavior, and the
reactions at the different [“excess”] give sufficient data required for the
determination of kinetic constants within a kinetic model.
A negative NLE was actually observed in Rh/binap-catalyzed
asymmetric addition of PhB(OH)2 (1) to 2-cyclohexenone (7),
giving phenylation product 82-4 ([R] > [S], Scheme 3, and squares
in Figure 2). The dimerization constant was estimated to be Kdimer
) 8 × 102 M-1 by fitting the deviation from the linear relationship
as well as the increase in the reaction rate to eq 3 (solid lines, Figure
2). By substituting this Kdimer value for the slope of eq 2
(k1/(2Kdimer)
0.5 ) 12 M-0.5 s-1), the rate constant for transmetalation
(12) The half-order kinetics in [catalyst] was reported in ref 10a.
(13) We observed that the hydrolysis is much faster than the insertion (ref 4).
(14) Kinetic modeling of the data to fit the proposed rate expression in eq 2
was carried out using the Excel least-squares program.
k1 is readily extracted to be k1 ) 0.5 M-1 s-1. Thus, we finally
obtained kinetic constants for both k1 and Kdimer. Unfortunately, it
is statistically difficult to extract the constant k2 under our
experimental conditions.
In conclusion, our detailed kinetic study and quantitative
simulation of nonlinear effect determined the rate constant for rate-
determining transmetalation and the dimerization constant, revealing
that the reaction mechanism involves the equilibrium between the
catalytically inactive dimeric hydroxorhodium complex [Rh(OH)-
((R)-binap)]2 (RR-4) and the active monomeric species R-4 and that
(15) For the first example, see: (a) Puchot, C.; Samuel, O.; Dunach, E.; Zhao,
S.; Agami, C.; Kagan, H. B. J. Am. Chem. Soc. 1986, 108, 2353. For
reviews, see: (b) Girard, C.; Kagan, H. B. Angew. Chem., Int. Ed. 1998,
37, 2922. (c) Blackmond, D. G. Acc. Chem. Res. 2000, 33, 402.
(16) (a) Kitamura, M.; Okada, S.; Suga, S.; Noyori, R. J. Am. Chem. Soc.
1989, 111, 4028. (b) Kitamura, M.; Suga, S.; Oka, H.; Noyori, R. J. Am.
Chem. Soc. 1998, 120, 9800.
(17) This type of mathematical treatment has been reported in refs 15c and
16b.
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