Mechanism of hydride transfer reaction from β-substituted carbanions to a carbocation

Article abstract of DOI:10.1246/cl.140385

Mechanism of hydride transfer reactions to form olefins is still a conundrum. Here, we propose an electron transfer (ET) followed by hydrogen atom transfer (HT) as the most likely mechanism for hydride transfer reactions from the hydride adducts of olefins (G-XH-) to a carbocation (T+) in acetonitrile. This is confirmed by the analysis of the energetics of each mechanistic step, estimated from ΔHH - (the hydride affinity) and redox potentials of the related species, and activation energetics calculated from rate constants of the hydride transfer from G-XH- to T+.

Full text of DOI:10.1246/cl.140385

Received: April 15, 2014 | Accepted: April 18, 2014 | Web Released: April 24, 2014
CL-140385
Mechanism of Hydride Transfer Reaction from β-Substituted Carbanions to a Carbocation
Fengrui Liu,* Shengyi Yan, and Xiaoqing Zhu*
State Key Laboratory of Elemento-Organic Chemistry, Department of Chemistry,
Nankai University, Tianjin 300071, P. R. China
(E-mail: zhenghang@mail.nankai.edu.cn)
Mechanism of hydride transfer reactions to form olefins is
still a conundrum. Here, we propose an electron transfer (ET)
followed by hydrogen atom transfer (HT) as the most likely
mechanism for hydride transfer reactions from the hydride
conventional synthetic strategies.17 The molar enthalpy changes
(¦Hrxn) of the hydride transfer reactions, standard one-electron
oxidation potentials, and standard one-electron reduction poten-
tials of the corresponding species, and the reaction rate constants
of the hydride transfer reactions in acetonitrile17 were deter-
mined. The detailed results are summarized in Table 1 and
Table 2.
¹
adducts of olefins (G-XH ) to a carbocation (T+) in acetonitrile.
This is confirmed by the analysis of the energetics of each
¹
mechanistic step, estimated from ¦HH (the hydride affinity)
and redox potentials of the related species, and activation
energetics calculated from rate constants of the hydride transfer
To elucidate the most likely mechanism of hydride transfer
¹
from G-XH to T+ in acetonitrile, the thermodynamic analysis
¹
from G-XH to T+.
Table 1. Molar enthalpy changes and redox potentials of the
related species in acetonitrile at 298 K (Scheme 2)
Olefin is a very important organic unsaturated compound,1
especially polar olefins.2-9 Olefins can be reduced by hydride
donors such as NADH, NaBH4, and LiAlH4. Because the
hydride anion can be split into two electrons and one hydrogen
atomic nucleus (or proton), these hydride transfer reactions
exhibit a variety of possible mechanisms. The achievements of
the related study focused on two aspects: (1) Thermodynamics.
This aspect is mainly concerned with the examining of
thermodynamic parameters (hydride affinity, hydrogen atom
affinity, and so on) of typical compounds such as olefins,10
aldehydes, ketones,11 and imines12 in CH3CN. (2) Kinetics.
On the basis of thermodynamics, a classical but new kinetic
equation to estimate activation energies has been developed.13
Furthermore, using the thermodynamic analysis combining the
kinetics to elucidate the hydride transfer reaction mechanism
has been successfully applied in the systems of caffeine14 and
vitamin C,15 which are bioactive. However, the hydride transfer
reaction mechanism of carbanions to form olefins has not been
studied yet. This is mainly because the kinetic data for the
simple hydride transfer are not available, affected by the
adduction16 between the carbanion and the hydride acceptor.
Through our tireless efforts, we found the proper acceptor
and successfully examined the kinetics of the simple hydride
transfer. Here, we report the hydride transfer reaction mecha-
nism of carbanions to form olefins (Scheme 1) using the
thermodynamic analysis combining the kinetics.
Eox(ZH)b/V
Ered(Z+)b/V
a
¦Hrxn
Species
¹1
/kcal mol
CV OSWV
CV OSWV
¹
G-XH
p-CH3O
p-CH3
p-H
p-Br
p-NO2
¹31.3
¹31.1
¹30.7
¹29.9
¹28.9
¹0.231 ¹0.261 ¹1.510 ¹1.481
¹0.223 ¹0.253 ¹1.471 ¹1.445
¹0.210 ¹0.240 ¹1.412 ¹1.382
¹0.191 ¹0.221 ¹1.321 ¹1.296
¹0.146 ¹0.176 ¹1.126 ¹1.097
TH
1.139
1.105 ¹0.627 ¹0.630
aObtained from the reaction heats by switching the sign.
bReproducible to 5 mV or better.
¹
Table 2. Rate constants of the hydride transfer from G-XH
to T+ in acetonitrile at 298 K together with the corresponding
activation energetics and KIE (Scheme 2)
¦Gb
/kcal mol
¹
a
c
G-XH
10¹2 © kobs
10¹2 © k(D)
KIEd
¹1
p-CH3O
p-CH3
p-H
p-Br
p-NO2
1.16
0.89
0.77
0.39
0.17
¹1
16.00
16.16
16.25
16.65
17.15
1.01
0.77
0.69
0.36
0.16
1.3
1.4
1.3
1.2
1.1
aThe unit is M¹1 s and the experimental error is within 5%.
bObtained from Eyring equation and the uncertainty is smaller
than 0.05 kcal mol¹1. cOne of the two H atoms was changed by
The substituted 5-benzyl-1,3-dimethyl-2,4,6-trioxohexahy-
¹
dropyrimidin-5-ide (G-XH ) and tris(4-methoxyphenyl)meth-
¹
ylium perchlorate (T+ClO4 ) were synthesized according to
the D atoms; the unit is M¹1 s and the experimental error is
¹1
d
within 5%. Obtained from KIE = kobs/(2k(D) ¹ kobs).
Scheme 1.
Scheme 2.
Chem. Lett. 2014, 43, 1125–1127 | doi:10.1246/cl.140385
© 2014 The Chemical Society of Japan | 1125

Scheme 3.
Table 3. Energetics of each mechanistic step of the hydride
¹
transfer reactions from G-XH to T+ shown in Scheme 3
Figure 1. Comparison of state energy changes for the three
¹1 a
¹
possible initial steps of the hydride transfer from H-XH to T+
(kcal mol
)
and the activation energy of the hydride transfer in acetonitrile.
¦H (or ¦G)
step a step b step c step d step e step f
Groups
Because the state energy change of step a is a quite large
negative value and that of step b is a positive value, it seems to
be that the one-step hydride transfer (step a) should be the most
likely process. However, the mass of an electron is much smaller
than that of the hydrogen atomic nucleus (proton), and the
electron transfer should be more favorable than the proton
transfer, which can receive the strong support from the Franck-
Condon principle.19 This is also to say that the mechanism is due
to the energetic of the initial electron transfer rather than that of
the overall hydride transfer, which was already verified and
accepted by most chemists.20 In addition, summarizing the
existing experimental facts, Cheng suggested that the one-step
hydride transfer mechanism is impossible when the energetic
p-CH3O ¹31.3
8.5
8.7
9.0
9.5
10.5
28.4
27.8
26.7
25.5
22.0
59.7
58.9
57.4
55.4
50.9
¹39.8 ¹59.7
¹39.8 ¹58.9
¹39.7 ¹57.4
¹39.4 ¹55.4
¹39.4 ¹50.9
p-CH3
p-H
p-Br
¹31.1
¹30.7
¹29.9
¹28.9
p-NO2
aThe state energy changes are scaled by using enthalpy
changes for steps c-e and by using free energy changes for
steps b and f.
platform12 on the possible mechanisms was first constructed
(Scheme 3), and the change of the standard state energy of each
reaction step (Table 3)18 can be estimated according to eqs 4-9,
of which eqs 6-9 were derived from three suitable thermody-
namic cycles according to Hess’ law.17
of the initial electron transfer is much smaller than 23.1
¹1 21
kcal mol
.
Therefore, on the basis of these theoretical
foundations and empirical rules, the only possible initial step
for the overall hydride transfer, whose initial electron transfer
energetic is much smaller than 23.1 kcal mol¹1, is the electron
transfer. Similarly, the quite large value of the state energy
changes for step d (PT) as well as the comparison of the state
energy changes for step d and the activation energies of the
hydride transfer reactions also ruled proton transfer out as the
second step of the overall hydride transfer. Therefore, the only
possible second step for the overall hydride transfer from
ꢀH ðstep aÞ ¼ ꢀHrxn
(4)
ð5Þ
ð6Þ
ꢀG ðstep bÞ ¼ ꢀF½EredðTþÞ ꢀ EoxðG-XHꢀÞꢁ
ꢀH ðstep cÞ ¼ ꢀHrxn ꢀ F½EredðG-XÞ ꢀ EoxðTHÞꢁ
ꢀH ðstep dÞ ¼ ꢀHrxn ꢀ F½EredðG-XÞ ꢀ EoxðTHÞꢁ
þ F½EredðTþÞ ꢀ EoxðG-XHÞꢁ
ð7Þ
ꢀH ðstep eÞ ¼ ꢀHrxn þ F½EredðTþÞ ꢀ EoxðG-XHÞꢁ ð8Þ
ꢀG ðstep fÞ ¼ F½EredðG-XÞ ꢀ EoxðTHÞꢁ
ð9Þ
¹
G-XH to T+ is the hydrogen atom transfer.
From Table 3, it is clear that for the five hydride transfer
reactions, the state energy change of step c (28.4-22.0
kcal mol¹1) is a quite large positive value. Therefore, it is
reasonable that the process of hydrogen atom transfer (step c)
can be ruled out as the initial step.
This was also confirmed by the comparison of the state
energy changes of the three possible initial steps and the
activation energies (Figure 1). Because the activation energies of
the reactions are much smaller than the corresponding standard
state energy changes of the initial hydrogen transfer, but larger
than those of the concerted hydride transfer (step a) or the
electron transfer (step b), the initial hydrogen atom transfer as
the isolated reaction step is impossible according to one of the
most fundamental reaction laws that the activation energy is
always larger than or at least equal to the corresponding standard
state energy change for any elementary reaction.
In fact, this multistep (e-H) mechanism could be further
verified by the value of KIE (about 1, in Table 2) when H and D
atoms were used as the isotopic atoms. This means that the rate-
determining step does not involve the transfer of the H nucleus.
Thus, it can be concluded that step a, step c, or step d is
impossible as the rate-determining step.
On the basis of the above, the only possible mechanism is
the electron transfer followed by the hydrogen atom transfer.
References and Notes
1
T. W. G. Solomons, C. B. Fryhle, Organic Chemistry, 8th
ed., Wiley, New York, 2004, pp. 287-370.
2
M. C. Haibach, S. Kundu, M. Brookhart, A. S. Goldman,
Acc. Chem. Res. 2012, 45, 947.
3
4
H. V. R. Dias, C. J. Lovely, Chem. Rev. 2008, 108, 3223.
O. Robles, S. O. Serna-Saldívar, J. A. Gutiérrez-Uribe, D.
1126 | Chem. Lett. 2014, 43, 1125–1127 | doi:10.1246/cl.140385
© 2014 The Chemical Society of Japan

Romo, Org. Lett. 2012, 14, 1394.
2012, 77, 6520.
5
K. Dhara, G. C. Midya, J. Dash, J. Org. Chem. 2012, 77,
8071.
15 X.-Q. Zhu, Y.-Y. Mu, X.-T. Li, J. Phys. Chem. B 2011, 115,
14794.
6
7
8
G. Zeni, R. C. Larock, Chem. Rev. 2004, 104, 2285.
Y.-X. Lu, Z. Guan, J. Am. Chem. Soc. 2012, 134, 14226.
Y.-T. Hong, A. Barchuk, M. J. Krische, Angew. Chem., Int.
Ed. 2006, 45, 6885.
M. K. Haldar, M. D. Scott, N. Sule, D. K. Srivastava, S.
Mallik, Bioorg. Med. Chem. Lett. 2008, 18, 2373.
16 Y. Lu, F. Qu, B. Moore, D. Endicott, W. Kuester, J. Org.
Chem. 2008, 73, 4763.
17 The details are listed in the Supporting Information.
Supporting Information is available electronically on J-
STAGE.
18 It should be pointed out herein that we used the term ¦GeT
to replace ¦HeT for the electron-transfer processes. The
validation of using ¦GeT instead of ¦HeT for electron-
transfer processes is that ¦SeT are negligible, which has been
verified by Arnett’s work. See: E. M. Arnett, K. Amarnath,
N. G. Harvey, J.-P. Cheng, J. Am. Chem. Soc. 1990, 112,
344.
9
10 a) X.-Q. Zhu, M. Zhang, Q.-Y. Liu, X.-X. Wang, J.-Y.
Zhang, J.-P. Cheng, Angew. Chem., Int. Ed. 2006, 45, 3954.
b) X.-Q. Zhu, H. Liang, Y. Zhu, J.-P. Cheng, J. Org. Chem.
2008, 73, 8403. c) Y. Cao, S.-C. Zhang, M. Zhang, G.-B.
Shen, X.-Q. Zhu, J. Org. Chem. 2013, 78, 7154.
11 X.-Q. Zhu, X. Chen, L.-R. Mei, Org. Lett. 2011, 13, 2456.
12 X.-Q. Zhu, Q.-Y. Liu, Q. Chen, L.-R. Mei, J. Org. Chem.
2010, 75, 789.
19 A. S. Coolidge, H. M. James, R. D. Present, J. Chem. Phys.
1936, 4, 193.
13 X.-Q. Zhu, F.-H. Deng, J.-D. Yang, X.-T. Li, Q. Chen, N.-P.
Lei, F.-K. Meng, X.-P. Zhao, S.-H. Han, E.-J. Hao, Y.-Y. Mu,
Org. Biomol. Chem. 2013, 11, 6071.
20 S. Fukuzumi, S. Koumitsu, K. Hironaka, T. Tanaka, J. Am.
Chem. Soc. 1987, 109, 305, and references therein.
21 J.-P. Cheng, Y. Lu, X. Zhu, L. Mu, J. Org. Chem. 1998, 63,
6108.
14 X. Han, W. Hao, X.-Q. Zhu, V. D. Parker, J. Org. Chem.
Chem. Lett. 2014, 43, 1125–1127 | doi:10.1246/cl.140385
© 2014 The Chemical Society of Japan | 1127