Predicting Counterion Effects Using a Gold Affinity Index and a Hydrogen Bonding Basicity Index

Article abstract of DOI:10.1021/acs.orglett.7b02829

We have developed a gold affinity index and hydrogen bonding basicity index for counterions and have used these indexes to forecast their reactivity in cationic gold catalysis.

Full text of DOI:10.1021/acs.orglett.7b02829

Letter
Cite This: Org. Lett. XXXX, XXX, XXX-XXX
pubs.acs.org/OrgLett
Predicting Counterion Effects Using a Gold Affinity Index and a
Hydrogen Bonding Basicity Index
Zhichao Lu, Junbin Han, Otome E. Okoromoba, Naoto Shimizu, Hideki Amii, Clau
́
dio F. Tormena,§
†
†
†
‡
‡
,†
,∥
Gerald B. Hammond,* and Bo Xu*
†
Department of Chemistry, University of Louisville, Louisville, Kentucky 40292, United States
‡
§
∥
Department of Chemistry and Chemical Biology, Graduate School of Engineering, Gunma University, Gunma 376-8515, Japan
Institute of Chemistry, University of Campinas, Campinas 13083-970, Brazil
College of Chemistry, Chemical Engineering and Biotechnology, Donghua University, 2999 North Renmin Lu, Shanghai 201620,
China
*
S Supporting Information
ABSTRACT: We have developed a gold affinity index and hydrogen
bonding basicity index for counterions and have used these indexes
to forecast their reactivity in cationic gold catalysis.
eactions that involve cationic species are among the most
R
important transformations in organic synthesis; counter-
ions often play a significant role in the efficiency of these
reactions. However, the selection of the counterion is, still,
1
mostly empirical. Cationic gold catalysis is a case in point; much
effort has been dedicated to understanding the effects of ligands
1
d,2
in gold catalysis,
but only recently have chemists begun to3
investigate the effects of counterion in gold-catalyzed reactions.
For example, Maier and co-workers studied counterion effects in
gold(I)-catalyzed hydroalkoxylation of alkynes, Echavarren
and co-workers did the same in gold(I)-catalyzed intermolecular
3d
3
e
cycloadditions, whereas Bandini, Macchioni, and co-workers
reported the effects of counterion in gold-catalyzed dearomatiza-
3j
tion of indoles with allenamides. However, a quantitative
analysis of counterion effects in gold catalysis is still elusive. The
selection of counterion is still empirical, and chemists test
different counterions during the process of reaction condition
optimization. We posited that one important barrier for a rational
understanding of counterion effect in cationic gold catalysis or
cationic catalysis in general is the lack of a quantitative
description of relevant physical properties of counterions.
Herein, we report a quantitative treatment of relevant physical
properties of counterions that affect their reactivity in cationic
gold catalysis.
Figure 1. Simplified representation of cationic metal-catalyzed
reactions.
5
exist as an ion pair rather than “free” ions. When the paired
+
−
1
2
cationic metal (M X ) interacts with RC and RC to produce
+
−
TS2, there will be a charge separation between M and X during
the formation of TS2. Thus, compared to the reaction of “free”
+
⧧
⧧
M , additional energy will be needed (ΔG
> ΔG TS1) to
TS2
overcome the Coulombic attraction. Our hypothesis is that in
many cases the counterion acts as a spectator and has limited
influence on the structures of the transition state (Figure 1b), so
the difference between ΔG and ΔG is mainly determined
by the affinity between M and X . Therefore, in general, a
In a simplified representation of cationic metal-catalyzed
+
reactions (Figure 1), a cationic metal catalyst (M ) will somehow
1
2
complex or connect to reactants (RC , RC , etc.) to form the
corresponding transition state (TS1), which in turn, leads to an
intermediate or product. In most theoretical treatments of
cationic gold catalysis, or transition-metal catalysis in general,
⧧
⧧
T2
T1
+
−
+
4
cationic metals are treated as “free” ions (M in Figure 1a). In
Received: September 10, 2017
low dielectric constant solvents, a cationic metal complex will
©
XXXX American Chemical Society
A
DOI: 10.1021/acs.orglett.7b02829
Org. Lett. XXXX, XXX, XXX−XXX

Organic Letters
Letter
catalyst that contains a weakly coordinating counterion (low
+
−
affinity between M and X ) will exhibit high reactivity.
But the above statement does have an exception. The
−
interaction between a pairing counterion (X ) and the
corresponding transition structure (TS2) is a long-range
electrostatic attraction (Figure 1b), which is usually relatively
weak. This long-range electrostatic attraction may exhibit limited
interaction with most atoms or groups, but if the transition-state
δ+
δ+
intermediate contains an active proton (e.g., O−H , N−H ),
which has the smallest mass among all atoms and is usually highly
charged, then a counterion may have significant impact (Figure
Figure 2. Correlation between calculated bonding energy and pKBHX
.
1
c). For example, it may impact the proton-transfer process via
3f
proton shuttling. This long-range interaction between an active
proton and the counterion can be classified as a hydrogen
6
bonding interaction, so the ability of a counterion to mediate the
proton transfer could be quantified by its hydrogen bonding
basicity. In these cases, therefore, counterions possessing high
hydrogen bonding basicity may play an important role in the
transition state.
First, we quantified the hydrogen bonding basicity of
counterions. In 2009, Laurence and co-workers reported a
comprehensive database of hydrogen-bond basicity (measured
7
by pKBHX). The pK of most compounds is in the range of 1−
Figure 3. Correlation between calculated H-bonding energy (ΔE) and
β.
BHX
6
, where a bigger number indicates a higher hydrogen-bond
basicity. In general, bigger and more charge-delocalized anions
show smaller hydrogen bonding basicity (I < Br < Cl <
OAc ). Most compounds in Laurence’s database are neutral
organic compounds, only few ionic compounds were reported.
We could use computational methods to predict the hydrogen
bonding basicity of counterions. Because the measurement of
pKBHX is based on the complexation of a hydrogen bond acceptor
with a substituted phenol, we calculated the H-bonding bonding
energies of phenol with various anions, and found out that these
7
−
−
−
strongest hydrogen bonding acceptor and CTf − is the weakest
3
−
(Table 1). Because different literature reports used different
hydrogen bond parameters, for convenience, we set up a
hydrogen bonding basicity index of counterions (HBI), assigning
−
−
an HBI of 10 to OAc and an HBI of 0 to CTf . In this scale, the
3
−
HBI of strong bases, like OH , will be greater than 10.
7
It should be noted that the hydrogen bonding basicity and
Brønsted basicity of counterions have a very poor correlation
(Figure 4). This means that a strong hydrogen bonding acceptor
is not necessarily a strong Brønsted base.
energies correlated very well with the experimental pK
corresponding n-Bu N salts (Table 1 and Figure 2). Similarly,
of the
BHX
+
7
4
Hunter and co-workers, very recently, developed a new hydrogen
8
bond basicity scale of anions (β) with more anions; our
calculated H-bonding bonding energies also correlated well with
the experimental parameter β (Figure 3). From our calculations,
−
among the more common counterions, acetate (OAc ) is the
Table 1. Hydrogen Bond Basicity Index (HBI) of Counterions
a
H-bonding energy ΔE
X−
OAc−
pKaH
4.7
(kJ/mol)
pKBHX
b
β
c
HBI
149.7
122.1
93.1
115.3
91.1
76.9
83.9
82.2
102.2
78.5
60.6
50.7
5.60
15.0
10
−
TFA
0.2
−2.8
−8
−9
−10
−14
<−10
<−10
<−10
<−10
<−10
7.2
4.3
6.5
4.1
2.6
3.4
3.2
5.2
2.8
1.0
0
−
Figure 4. Lack of correlation between Brønsted basicity (pK ) and
TsO
11.3
12.1
10.6
8.9
aH
−
hydrogen bonding index.
Cl
4.26
2.80
−
Br
I−
−
Then we proceeded to quantify the gold affinity index of
counterions. The affinity of the counterion toward cationic gold
will depend on the size and charge distribution of the counterion.
Unfortunately, comprehensive data about counterions’ gold
affinity is not available; only a limited set is available in the
OTf
9.4
−
PF6
7.0
−
BF4
−
SbF6
−
NTf2
7.3
3d
−
literature. We used our calculated gold-counterion dissociation
CTf3
14
energies to describe their bonding affinity. In our calculations,
−
a
among the more common counterions, iodide (I ) is the
Bonding energies were calculated at B3LYP/6-31g level of theory
b
+
c
strongest counterion and SbF6− is the weakest (Table 2).
without solvent. pKBHX of corresponding n-Bu N salts. Exper-
4
imental H-bonding bond parameter by Hunter and co-workers.
Similarly, as in the previous section, we set up the gold affinity
B
DOI: 10.1021/acs.orglett.7b02829
Org. Lett. XXXX, XXX, XXX−XXX

Organic Letters
Letter
−
Table 2. Gold Affinity Scale of Counterions
low gold affinity (e.g., SbF ) did exhibit fast kinetics. For
6
reactions where there is an active proton involved (e.g.,
cyclization of propargyl amide 3, Table 3b), counterions with
high hydrogen bonding (e.g., OTf ) may assist in the proton
transfer and speed up the reaction.
counterion with very high gold affinity (e.g., OAc ) acted as
inhibitor. It should be noted that counterions are not the only
hydrogen bond acceptors; starting materials and products or
16
−
dissociation energy ΔE
gold affinity index
3a−g,17
a
In both reactions, a
counterion
(kJ/mol)
(GAI)
−
I−
143.8
53.9
67.7
74
10
5.2
6.0
6.3
6.1
3.8
2.9
2.4
0.5
0.2
0
−
−
Cl
Br
18
even water clusters could assist proton transfer.
−
TFA
Our indexes can also be used to rationalize the regioselectivity
results found in the literature. For example, counterions play a
key role in the synthesis of disubstituted pyrrole 6 (Scheme
−
OAc
70.6
28
−
OTs
−
NTf2
10.4
0
19
−
−
1a). A gold catalyst with a OTs counterion promotes a 1,2-H-
OTf
−
BF4
−35.1
−40.5
−44.3
<−45
−
Scheme 1. Literature Examples Where the Effect of
Counterions on Regioselectivity Can Be Rationalized
CTf3
−
SbF6
Al[(CF ) C−
<0
3
3
−
O)]
4
−
BArF4
<−45
<0
a
9
Theoretical calculations using B3LYP hybrid functional and
1
0
11
Lanl2DZ with pseudopotential for Au, an all-electron QZP basis
set for Sb and 6-311++g(d.p) for the remaining atoms. The solvent
effect was included using the SMD model for DCM. All calculations
12
13
were performed using Gaussian09; see the Supporting Information.
−
index of counterions (GAI) by assigning a GAI of 10 to I and a
−
GAI of 0 to SbF . In general, large, negatively charged, and
6
highly delocalized counterions have smaller affinity toward
−
−
−
cationic gold (e.g., SbF , CTf ). But counterions like OAc ,
6
3
which are relatively small and have a more localized charge, form
strong interactions with the cationic gold metal center. These
properties may explain why they are rarely used in gold catalysis.
It also should be noted that the hydrogen bonding basicity and
the gold affinity index of counterions have a very poor correlation
(
Supporting Information).
Our indexes can be used to rationalize the kinetic effects of
counterions in gold-catalyzed reactions. For reactions in which
no active proton is involved (e.g., cycloisomerization of 1,6-
1
5
enyne, Table 3a), gold catalysts containing counterions with
shift (or proton shuttling) product, whereas a gold catalyst with
OTf promotes a 1,2-Ph-shift product. This experimental
−
Table 3. Counterion Effects on the Kinetics
outcome can be easily rationalized using our higher hydrogen
−
−
basicity index (OTs = 4.3 vs OTf = 3.4) since the value for
−
OTf to mediate the proton transfer is much less that than that of
OTs . Similarly, in the regio-divergent behavior of counterions
−
during the gold-promoted synthesis of bromofuran 8 (Scheme
20
−
1
b), a gold catalyst with a OTf counterion promotes the 1,2-
H-shift (or proton shuttling) product, whereas a gold catalyst
with a SbF6− counterion furnishes the 1,2-Br-shift product.
Again, these results can be easily rationalized by the higher
−
−
hydrogen basicity of OTf (HBI = 3.4) vs SbF (HBI = 2.8). As
6
−
a result, OTf shows a stronger ability to mediate the proton
−
transfer compared to SbF .
6
Our model is not just limited to cationic metal catalysis. It
could be applied to cationic catalysis in general. For example, in
21
organo-enamine catalysis, an active proton is often involved
e.g., the enammonium intermediate). By examining the
MacMillan imidazolidinone catalyzed Michael addition (Table
(
22
4
), catalysts with high hydrogen bonding basicity showed
higher reaction rates, as expected. Of course, if the counterion is
too basic (e.g., acetate), the reaction cannot proceed because
both formation of enamine and the regeneration of the secondary
21
amine catalyst need an acidic environment.
C
DOI: 10.1021/acs.orglett.7b02829
Org. Lett. XXXX, XXX, XXX−XXX

Organic Letters
Letter
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index (HBI)
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X−
OTf−
)
rate
(pKaH
−14
−9
3.4
4.1
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Br−
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AUTHOR INFORMATION
Corresponding Authors
■
*
*
2
(
8
́
́
, A. J. Am. Chem. Soc. 2008, 130,
E-mail: gb.hammond@louisville.edu.
E-mail: bo.xu@dhu.edu.cn.
ORCID
̃
̃
Car
2
́
denas, D. J.; Echavarren, A. M. Angew. Chem., Int. Ed. 2004, 43,
402−2406. (b) Cabello, N.; Jimen
́
ez-Nunez, E.; Bunuel, E.; Cardenas,
́
̃
̃
́
Gerald B. Hammond: 0000-0002-9814-5536
Notes
D. J.; Echavarren, A. M. Eur. J. Org. Chem. 2007, 2007, 4217−4223.
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The authors declare no competing financial interest.
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015, 5, 3911−3915. (b) Wang, W.; Kumar, M.; Hammond, G. B.; Xu,
ACKNOWLEDGMENTS
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L.; Biasiolo, L.; Del Zotto, A.; Tarantelli, F.; Zuccaccia, D. ACS Catal.
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We are grateful to the National Science Foundation for financial
support (CHE-1401700). B.X. is grateful to the National Science
Foundation of China (NSFC-21472018). C.F.T. is grateful to
Sao Paulo Research Foundation (FAPESP-2015/08541-6) and
̃
CNPq for fellowships.
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Org. Lett. XXXX, XXX, XXX−XXX