Direct measurement of the thermodynamics of vinylarene hydroamination

Article abstract of DOI:10.1021/ja062773e

The thermodynamics for intermolecular hydroamination of vinylarenes with arylamines have been measured directly by conducting the addition processes, as well as cleavage of the addition products, under conditions in which amine, vinylarene, and phenethylamine are all present. The reaction of N-methylaniline with styrene is exothermic by about 10 kcal/mol but nearly thermoneutral in free energy. The free energies for additions of various primary arylamines to styrene and for additions of primary arylamines to indene, dihydronaphthalene, and two vinylarenes range from 1.3 to -3.5 kcal/mol (K = 0.16-155 M^-1). The steric properties of the nucleophile significantly influenced the equilibrium constant for addition, but the electronic properties of the nucleophile had a minor effect on this equilibrium constant. These measurements have led to the first successful intermolecular addition of aniline to indene and 1,2-dihydronaphthalene and shed light on factors requiring consideration when choosing substrates and reaction conditions for this transformation. Copyright

Full text of DOI:10.1021/ja062773e

Published on Web 06/22/2006
Direct Measurement of the Thermodynamics of Vinylarene Hydroamination
Adam M. Johns, Norio Sakai, Andre´ Ridder, and John F. Hartwig*
Department of Chemistry, Yale UniVersity, Post Office Box 208107, New HaVen, Connecticut 06520-8107
Received April 20, 2006; E-mail: john.hartwig@yale.edu
Table 1. Thermodynamics of Hydroamination
The addition of amines to olefins catalyzed by transition metals
has been a long-term target for catalysis,1,2 and efforts to develop
catalysts for this reaction have intensified in recent years.3,4,5
Reviews have stated that the hydroamination of olefins is thermo-
dynamically favored,2 but experimental equilibrium constants,
enthalpies, and entropies for olefin hydroamination in solution are
lacking.
The enthalpy for additions of amines to olefins has generally
been predicted from bond dissociation energies of only model
substrates, such as ethylene and ammonia, and the entropy for this
reaction in solution has been estimated from typical differences in
translational entropy upon formation of a 1:1 adduct or ∆S values
in the gas phase.6 Because the thermodynamics for hydroamination
are close to thermoneutral, precise measurements of the thermo-
dynamic parameters for the reactions between amines and olefins
of varied structures are needed to establish benchmark values that
can be used to predict which types of hydroaminations will be
favorable and which will be unfavorable. To fill this void of basic
information on olefin hydroamination, we report direct measure-
ments of the equilibrium constants for addition of aromatic amines
with varied steric and electronic properties to several types of vinyl-
arenes. An appreciation of the thermodynamic constraints of this
process has allowed us to observe the first intermolecular additions
of amines to internal olefins that lack the high ring strain of
norbornene.7
a Catalyst composition: (A) Forward: 2 mol % tBuXantphosPd(OTf)2.
Backward: 2 mol % CpPd(η3-allyl)/tBuXantphos/HOTf. (B) Forward: 10
mol % Pd(TFA)2/DPPF/HOTf. Backward: 10 mol % CpPd(η3-allyl)/DPPF/
HOTf. (C) Forward: 5 mol % Pd(TFA)2/DPPF/HOTf. Backward: 5 mol
% CpPd(η3-allyl)/DPPF/HOTf.
We began our assessment of the thermodynamics of hydroami-
nation by studying the addition of N-methylaniline to styrene.
Preliminary results showed that a series of catalysts formed the
addition product in similar yields and that the major material in
solution, other than the addition product, was the starting olefin
and the aromatic amine. These observations suggested that this
hydroamination might be controlled by thermodynamics rather than
reaction rate and catalyst stability.
Figure 1. van’t Hoff plot of eq 1.
To determine the enthalpic and entropic contribution to this
equilibrium constant, we measured this equilibrium constant at
different temperatures. A van’t Hoff plot of these data showed that
the enthalpy for addition was -10.0 ( 0.8 kcal/mol and that the
entropy was -27 ( 4 eu (Figure 1). Thus, the hydroamination is
favored enthalpically, but this favorable enthalpy is counterbalanced
by a nearly equal T∆S term.
To determine the thermodynamics for this process, we conducted
the addition of N-methylaniline to styrene, as well as the cleavage
of the N-methyl-N-(1-phenylethyl)aniline, to form free styrene and
N-methylaniline (eq 1). The use of the wide-bite angle bisphosphine
Xantphos and a Pd0 precatalyst for the retrohydroamination4 allowed
us to conduct the reaction in both directions with acceptable rates
and minimal catalyst decomposition. The addition of N-methyl-
aniline to styrene and the cleavage of N-methyl-N-(1-phenylethyl)-
aniline at the same starting concentrations formed equivalent
amounts of reaction components. The equilibrium constant for the
addition process was found to be K ) 1.5 ( 0.1 M-1 at 80 °C and
K ) 0.52 ( 0.05 M-1 at 110 °C. This value is shown as entry 1 of
Table 1.
Considering that several review articles2 state that the unfavorable
entropy of the intermolecular addition makes it necessary to conduct
the reaction at low temperatures, a comment about the effect of
temperature on equilibrium is warranted. The temperature depen-
dence of an equilibrium constant and, therefore, the conversion
results from ∆H. Le Chaˆtelier’s principle implies that the equilib-
rium constant for an exothermic reaction will be larger at lower
temperatures than at higher temperatures.
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10.1021/ja062773e CCC: $33.50 © 2006 American Chemical Society

C O M M U N I C A T I O N S
Additional equilibrium constants for additions of amines to
vinylarenes are shown in Table 1. Because the palladium-catalyzed
additions of electron-rich anilines occur in higher yields than
additions of electron-poor anilines4,5 and additions to more electron-
poor vinylarenes occur in higher yields than additions to more
electron-rich vinylarenes,5 we sought to determine if the higher
yields for these classes of substrates resulted from thermodynamic
or purely kinetic factors. Thus, we measured the equilibrium con-
stants for the addition of 4-methoxy-N-methylaniline to styrene
(Table 1, entry 2) and for the addition of N-methylaniline to 2-vinyl-
naphthalene (entry 3). The equilibrium constants for these additions
(2.4 ( 0.1 M-1, and 1.30 ( 0.01 M-1) are similar to the equilibrium
constant for the addition of N-methylaniline to styrene (1.5 ( 0.1
M-1) in entry 1. Therefore, the electronic effect on this reaction is
almost purely a result of kinetic, not thermodynamic, factors.
In contrast, steric properties of the amine significantly affected
the equilibrium constant. The addition of aniline to styrene occurred
at a higher conversion than the addition of N-methylaniline under
equilibrium conditions. By conducting the forward and reverse of
the addition of m-anisidine8 to styrene (Table 1, entry 4), the
equilibrium constant for the addition process was found to be 155
( 1 M-1. This value is substantially larger than the value for the
addition of N-methylaniline.
(eq 2). As shown in eq 3, increasing the ratio of styrene to
N-methylaniline to 10:1 (4.4 and 0.44 M, respectively) allowed the
reaction to form the addition product in 87% yield. Unfortunately,
the equilibrium for addition to 1,2-dihydronaphthalene was too
unfavorable to obtain high yields.
In conclusion, we have shown the importance of considering
the thermodynamics for additions of amines to olefins when
targeting catalytic hydroamination processes. We have shown that
the reactions are exothermic but nearly ergoneutral. Clearly an
intramolecular reaction will not be constrained by as large a negative
entropy, but an intramolecular reaction that generates a strained
ring system is likely to experience similar and counterbalancing
enthalpies from ring strain. At the same time, consideration that
the reaction yield is controlled in large part by thermodynamics
allows one to conduct reactions under conditions in which the
addition processes do occur in high yields.
Acknowledgment. We thank the NIH (GM-55382) for support
of this work. N.S. thanks Tokyo University of Science (TUS) for
support of his stay.
Supporting Information Available: Spectroscopic and analytical
data of new compounds and experimental procedures. This material is
available free of charge via the Internet at http://pubs.acs.org.
Because disubstituted olefins are more stable than monosubsti-
tuted olefins,9 we also assessed the thermodynamics for the addition
of m-anisidine to indene and 1,2-dihydronaphthalene. No metal-
catalyzed additions of amines to these olefins have been reported.7f
In the presence of a combination of Pd(TFA)2 (TFA ) trifluoro-
acetate), 1,1′-bis-(diphenylphosphino)ferrocene, and triflic acid, the
addition of aniline occurred to each of these olefins to generate
equilibrium mixtures of reactants and products.
The addition of aniline to indene at a concentration of aniline of
about 2 M with 4 equiv of indene formed the Markovnikov addition
product in 50% yield, as determined by GC. The bulk of the
remaining material was the starting indene and arylamine. Reaction
of N-(3-methoxyphenyl)-2,3-dihydro-1H-inden-1-amine with the
same catalyst generated free indene and m-anisidine. From the ratio
of indene, m-anisidine, and the addition product generated from
both the forward and reverse reactions (Table 1, entry 5), an
equilibrium constant of 0.69 ( 0.05 M-1 was calculated.
Likewise, the addition of aniline to 1,2-dihydronaphthalene
occurred in yields that were limited by thermodynamics. The
reaction of 1 M olefin with 1 M aniline generated the addition
product in 8% yield. Again, cleavage of the addition product
generated free olefin and free amine. From the ratio of 1,2-
dihydronaphthalene, m-anisidine, and the addition product generated
from reactions run in the forward and reverse directions, (Table 1,
entry 6), an equilibrium constant of 0.16 ( 0.04 M-1 was calculated.
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