C O M M U N I C A T I O N S
Table 1. Comparison of Calcium- and Strontium-Mediated
Intermolecular Hydroamination
3
4
entry
R
amine
time (h)
conv (%)
time (h)
conv (%)
1
2
3
4
5
OMe
Me
H
Cl
Cl
PhCH2NH2
PhCH2NH2
PhCH2NH2
NH(CH2)5
NH(CH2)4
168
60
48
24
2
17
70
92
60
95
144
28
24
17
1
63
84
78
79
65
1
from H NMR monitoring at four different reaction temperatures.
Arrhenius analyses derived from the two sets of kinetic data afforded
activation energies (Ea) of 12.7 and 17.2 kcal mol-1 for the calcium-
and strontium-catalyzed reactions, respectively. Although the increased
rate of hydroamination provided by the strontium amide 4 thus appears
counterintuitive, Eyring analyses of the kinetic data provided a telling
insight into the nature of the catalytic reactions. The values derived
for the activation enthalpies (∆Hq ) 12.2 kcal mol-1 for 3 and 17.0
kcal mol-1 for 4) were comparable to the Ea values. The entropy of
activation (∆Sq) for 3 (-40.1 cal mol-1 K-1), however, was found to
be considerably more negative than that for 4 (-22.0 cal mol-1 K-1),
and thus, ∆Gq values of 24.1 and 23.4 kcal mol-1 were obtained for
the reactions catalyzed by 3 and 4, respectively, at 298 K. Use of the
Figure 2. Electron density difference maps for the alkene insertion (a)
transition state and (b) intermediate for the Mg-mediated cycle. The density
difference is relative to a promolecule composed of spherical atoms; solid
lines indicate areas of buildup in electron density, and dotted lines indicate
areas of depletion. The slice shown was taken in the C1-C2-N3 plane,
and the contour interval is 0.003.
may therefore be viewed as the result of not only the greater polarity
(and consequent superior ability to induce a dipole in the nonpolarized
ethene substrate) of the Ca-N bond but also the greater polarizability
of the Ca2+ cation.
This deduction was reinforced by analogous calculations with M
as either Sr or Ba. Although both computed cycles also indicated rate-
determining alkene insertion (Figure 1), the trend toward reduced
barrier heights with increasing atomic weight did not continue.
Although ∆Gq for insertion when M ) Sr (15.5 kcal mol-1) was
slightly less than that when M ) Ca, a significant increase was
observed for M ) Ba (∆Gq ) 18.6 kcal mol-1). Following our
postulate above, we attribute this latter result to the highly diffuse and
thus weakly polarizing nature of the Ba atom, which is unable to
sufficiently polarize the Ba-N bond or stabilize the charge accruing
on C1 of the ethene CdC unit.
Although synthetic accounts of the more challenging intermolecular
variant of this reactivity by organolanthanide catalysis are limited, vinyl
arene hydroamination has been reported to proceed with good isolated
yields and excellent anti-Markovnikov regioselectivity.2,6 We thus
carried out a preliminary study of intermolecular hydroamination
catalysis of vinyl arenes and conjugated dienes with a variety of
primary, secondary and N-heterocyclic amines. In line with the
expectation provided by the DFT studies, stabilization of the incipient
benzylic charge induced by formation of the proposed four-membered
transition state provided exclusive access to the anti-Markovnikov
products. The reactions were successfully carried out employing the
homoleptic calcium and strontium amides [M{N(SiMe3)2}2]2 [M )
Ca (3), Sr (4)], and typical results are summarized in Table 1.
Analogous reactions with Mg- and Ba-based species were found to
be very slow and are thus not included in further discussion.
In every case, strontium catalyst 4 was found to display a higher
activity than the calcium complex 3, and in general, comparable
conversions were achieved in approximately half the reaction time.
When less-active substrates were applied, the difference was even more
significant (Table 1, entries 1-3).
larger alkaline-earth cation (six-coordinate radii: Ca2+, 114 pm; Sr2+
,
132 pm)3 thus provides a distinct and influential entropic advantage
that is most likely a reflection of the relative “tightness” of the four-
membered insertion transition states required to assemble the substrate
components about the respective group 2 metal centers. Although
exactly analogous data have not been reported for any lanthanocene-
catalyzed system, it is noteworthy that reported ∆Sq values for both
inter- and intramolecular processes are on the order of -26.3 cal mol-1
K-1, and it has been argued that the transition states are thus highly
organized/constrained.2,6 In conjunction with the influence of cation
polarizability inferred from our gas-phase computational study,
therefore, it is apparent that the hydroamination activity of the group
2 elements should not be viewed as simply “lanthanide-mimetic”.
Rather, their larger variations in size, electropositive character, and
charge density may afford even greater scope for tuning and selection
of complementary reactivity within a specific catalytic mechanism.
Supporting Information Available: Full experimental details for the
DFT calculations, catalytic reactions, and kinetic analyses. This material
Acknowledgment. We thank GlaxoSmithKline for the generous
endowment (to A.G.M.B.), the Royal Society for a University Research
Fellowship (to M.S.H.), and GlaxoSmithKline for generous support
of our studies.
References
(1) (a) Crimmin, M. R.; Casely, I. J.; Hill, M. S. J. Am. Chem. Soc. 2005, 127,
2042. (b) Crimmin, M. R.; Arrowsmith, M.; Barrett, A. G. M.; Casely, I. J.;
Hill, M. S.; Procopiou, P. A. J. Am. Chem. Soc. 2009, 131, 9670.
(2) Hong, S.; Marks, T. J. Acc. Chem. Res. 2004, 37, 673.
Further insight into the improved catalytic performance of the
strontium amide was provided by a kinetic analysis of the reaction of
the cyclic secondary amine piperidine with styrene, employing an
excess of styrene to provide a pseudo-first-order reaction. Although
the exact rate law was not determined and substrate inhibition may
play a key role,1b the addition of piperidine to styrene catalyzed by 3
and 4 provided two series of pseudo-first-order rate constants obtained
(3) Shannon, R. D. Acta Crystallogr. 1976, A32, 751.
(4) (a) Barrett, A. G. M.; Crimmin, M. R.; Hill, M. S.; Kociok-Ko¨hn, G.;
Procopiou, P. A. Inorg. Chem. 2008, 47, 7366. (b) Arrowsmith, M.; Hill,
M. S.; Kociok-Ko¨hn, G. Organometallics 2009, 28, 1730.
(5) Datta, S.; Gamer, M. T.; Roesky, P. W. Organometallics 2008, 27, 1207.
(6) (a) Li, Y.; Marks, T. J. Organometallics 1996, 15, 3770. (b) Ryu, J.-S.; Li,
Y.; Marks, T. J. J. Am. Chem. Soc. 2003, 125, 12584.
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