Selecting double bond positions with a single cation-responsive iridium olefin isomerization catalyst

Article abstract of DOI:10.1021/jacs.0c11601

The catalytic transposition of double bonds holds promise as an ideal route to alkenes of value as fragrances, commodity chemicals, and pharmaceuticals; yet, selective access to specific isomers is a challenge, normally requiring independent development of different catalysts for different products. In this work, a single cation-responsive iridium catalyst selectively produces either of two different internal alkene isomers. In the absence of salts, a single positional isomerization of 1-butene derivatives furnishes 2-alkenes with exceptional regioselectivity and stereoselectivity. The same catalyst, in the presence of Na⁺, mediates two positional isomerizations to produce 3-alkenes. The synthesis of new iridium pincer-crown ether catalysts based on an aza-18-crown-6 ether proved instrumental in achieving cation-controlled selectivity. Experimental and computational studies guided the development of a mechanistic model that explains the observed selectivity for various functionalized 1-butenes, providing insight into strategies for catalyst development based on noncovalent modifications.

Full text of DOI:10.1021/jacs.0c11601

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Selecting Double Bond Positions with a Single Cation-Responsive
Iridium Olefin Isomerization Catalyst
Andrew M. Camp, Matthew R. Kita, P. Thomas Blackburn, Henry M. Dodge, Chun-Hsing Chen,
and Alexander J. M. Miller*
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ABSTRACT: The catalytic transposition of double bonds holds promise
as an ideal route to alkenes of value as fragrances, commodity chemicals,
and pharmaceuticals; yet, selective access to specific isomers is a
challenge, normally requiring independent development of different
catalysts for different products. In this work, a single cation-responsive
iridium catalyst selectively produces either of two different internal
alkene isomers. In the absence of salts, a single positional isomerization
of 1-butene derivatives furnishes 2-alkenes with exceptional regioselec-
tivity and stereoselectivity. The same catalyst, in the presence of Na+,
mediates two positional isomerizations to produce 3-alkenes. The
synthesis of new iridium pincer-crown ether catalysts based on an aza-
18-crown-6 ether proved instrumental in achieving cation-controlled
selectivity. Experimental and computational studies guided the develop-
ment of a mechanistic model that explains the observed selectivity for various functionalized 1-butenes, providing insight into
strategies for catalyst development based on noncovalent modifications.
field of alkene hydroformylation, with additives (including
alkali metal cations)26−31 interacting with the catalyst to tune
the aldehyde product regioselectivity between terminal or
secondary positions.32 Finding a single catalyst that can access
two states capable of a dramatic switch in regioselectivity
remains a challenge in hydroformylation.32,33 The challenge
seems even more daunting for olefin isomerization, where two
states must discriminate between sterically similar internal
olefins. We are not aware of any examples of olefin
isomerization catalysts with additive-responsive selectivity.
Herein, we introduce new pincer-crown ether iridium
hydride catalysts featuring hemilabile aza-18-crown-6 ether
receptors that enable olefin isomerization with cation-
programmable regioselectivity. In its native state, the pincer-
crown ether catalyst isomerizes a range of 1-butenes to the 2-
butene regioisomer with high E stereoselectivity (Figure 1C).
In the presence of Na+ salts, however, the same catalyst
produces 3-butenes, exhibiting high degrees of regioselectivity
control between two internal double bond positions.
Experimental and computational studies provide insight into
1. INTRODUCTION
Olefins are essential intermediates and products in the
fragrance, commodity chemicals, and pharmaceutical indus-
tries.1 Positional isomerization of double bonds offers a highly
attractive route to internal olefins, given the wide availability of
terminal olefins and the perfect atom economy of double bond
transposition.2−8 However, preparing specific isomers with
high stereo- and regioselectivity remains a major challenge in
catalyst design.
When the desired olefin is by far the most stable isomer,
classical methods that use strong acid or high temperature
work well.9,10 Isomerization of allylbenzene derivatives is a
prime example, with only two possible products and (E)-β-
methylstyrene strongly thermodynamically favored.4 When
there are many energetically similar possible products of
double bond positional isomerization, conversely, a poorly
selective distribution of alkenes is typically obtained.
Transition metal catalysts with custom-tailored supporting
ligands can facilitate selective isomerization, exemplified by
systems capable of a single transposition converting 1-alkenes
to (E)-2-alkenes11−16 or (Z)-2-alkenes.17−19
Received: November 4, 2020
Published: February 8, 2021
The current paradigm for controlling selectivity is that for
each different product, a new metal/ligand combination is
needed (Figure 1A). An alternative approach uses a single
metal/ligand combination in conjunction with external
additives to control the selectivity (Figure 1B).20−25 Non-
covalent modification has been particularly impactful in the
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(labeled “b”) were compared with unsubstituted variants
(labeled “a”), based on recent studies showing that methoxy
substitution prevents side reactions during catalysis.38,39
A
biphasic synthesis proved essential for removal of chloride,
with treatment of the previously reported aza-18-crown-6-
ether-based chloride complexes 1-18c6a/b40 with NaBArF
4
(ArF = 3,5-bis(trifluoromethyl)phenyl) in 1:1 CH2Cl2:H2O
producing cationic aqua hydride complexes 3-18c6a/b (Figure
2). Heating solid samples of 3-18c6a/b at 145 °C under
vacuum overnight yielded the desired complexes 2-18c6a/b
(Figure 2). The complexes were characterized by multinuclear
NMR spectroscopy, high-resolution mass spectrometry, and
single crystal X-ray crystallography. The purity of the methoxy-
containing complexes was established by NMR spectroscopy
and elemental analysis; the purity of the unsubstituted variants,
which were not used in the following catalysis studies, was
assessed by NMR spectroscopy.
Initial attempts at chloride abstraction from 1-18c6a using
NaBArF (Figure 2) gave a single product, but an X-ray
4
diffraction study of the resultant crystals revealed a Na+ adduct,
[κ4-(18c6NCOPiPr)Ir(H)(Cl)@Na][BArF ] (1-18c6a@Na, Fig-
4
ure 2), with Na+ unexpectedly intercalated by the crown ether
and the (unabstracted) Cl− bridging to the Ir center. Similar
species were proposed as intermediates in on/off rate-
switchable isomerization by the 15-crown-5-based catalyst,34
although these were not structurally characterized.
Figure 1. Product selectivity can be tuned via the traditional approach
involving preparation of several new synthetically modified catalysts
(A) or via an emerging approach based on noncovalent modifications
of a single catalyst system (B).
Both of the pentadentate-bound cationic hydride complexes
2-18c6a/b exhibit dynamic behavior in NMR studies. A single
broad resonance is observed in each 31P{1H} NMR spectrum,
catalyst design principles and thermodynamic landscapes
required to access high selectivity in 1-butene isomerizations.
1
2. RESULTS
and each H NMR spectrum exhibits broadening in many
resonances of the crown ether ring. Dynamic behavior was
seen as low as −70 °C, suggesting crown ether oxygen
hemilability with facile exchange between bound and free
oxygen atoms.
Synthesis of Catalysts Based on Aza-18-crown-6
Ether. Previous studies focused on aza-15-crown-5-ether-
based pincer complexes, which performed a single positional
isomerization of allylbenzene with rate acceleration by Li+ salts
(but without any change in selectivity).34,35 We hypothesized
that iridium complexes containing an aza-18-crown-6 ether
would show higher activity, based on binding affinity studies
showing very strong and selective binding of Na+,36,37 enabling
the transposition of double bonds over multiple positions.
The synthetic route to cationic hydride complexes amenable
to olefin binding is summarized in Figure 2. Complexes with
methoxy groups in the arene backbone of the pincer ligand
Comparative X-ray diffraction (XRD) studies provided
further insight into linkage isomers. The solid-state structure
of 2-18c6a features two crown ether oxygen atoms donating to
the Ir center (Figure 3A), the oxygen closest to the amine
(O1) and its nearest neighbor (O2). Complex 2-18c6b,
however, adopts a different linkage isomer in the solid state,
with the two oxygen atoms proximal to the amine (O1 and
O5) donating to Ir. Distinct linkage isomers were also
observed in the structures of previously reported complexes
2-15c5a and 2-15c5b.39,41 Computational studies are con-
sistent with the linkage isomers being energetically similar
(within 3 kcal/mol), slightly favoring the isomer with amine-
adjacent ethers bound to iridium (Figure S55).
Structural comparisons of the aqua complexes are also
instructive. As shown in Figure 3B, the large macrocycle-
containing complexes 3-18c6a and 3-18c6b feature one crown
ether oxygen (O1) binding to the Ir center in the primary
coordination sphere, while the bound water engages in
hydrogen bonding with two other crown ether oxygen atoms
(O2 and O5). The hydrogen bonding network in the
secondary coordination sphere draws the crown ether
macrocycle around the metal center. The flexibility of the
larger 18-crown-6 macrocycle enables the ring to fully
encapsulate the water ligand, a motif also seen in large
metalla-crown complexes with water ligands.42 The 15-crown-5
macrocycle only interacts with the water ligand from one side.
An important conclusion of the synthetic and structural
studies is that the size of the macrocycle and the presence of a
methoxy group in the pincer backbone induce only subtle
Figure 2. Synthesis of 18-crown-6-based Ir pincer complexes and
molecular structure of 1-18c6a@Na from an X-ray diffraction study
(BArF anion and cocrystallized solvent omitted for clarity, ellipsoids
4
at 50% probability); the hydride was located in the difference map.
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Figure 3. Molecular structures of (A) 2-18c6a/b, previously published 2-15c5a,41 and 2-15c5b; and (B) 3-18c6a/b and 3-15c5a/b from X-ray
diffraction (ellipsoids at 50% probability). BArF − counteranions and cocrystallized solvent are omitted for clarity. See SI for more details.
4
changes in catalyst structure and hemilability dynamics. Thus,
we anticipated that differences in catalytic activity would be
dominated by changes in cation−macrocycle binding affinity.
In light of previous results showing superior performance for 2-
15c5b over 2-15c5a,39 subsequent studies focused on
methoxy-containing catalysts.
Cation-Switchable Regioselectivity in the Isomer-
ization of 4-Phenyl-1-Butene Derivatives. To probe the
ability of 2-18c6b to produce different internal olefins with
different additives, a variety of 4-aryl-1-butenes were treated
with 1 mol % 2-18c6b at 50 °C, with or without NaBArF .
4
Table 1 shows that Na+ controls the regioselectivity and
stereoselectivity of the isomerization product. Regioisomer b is
formed in 84 to 95% yield and 7:1 to 15:1 E:Z selectivity in the
Influence of Macrocycle Size on Cation-Controlled
Olefin Isomerization. To assess the performance of the new
18-crown-6-based catalysts, isomerization of 4-phenyl-1-butene
(4a) to 4-phenyl-2-butene (4b) was monitored at room
temperature by NMR spectroscopy (Figure 4A). For
simplicity, terminal olefins are labeled a, the isomer with the
double bond in the adjacent internal position is labeled b, and
the next internal position is labeled c. In the absence of salt, 1
mol % 2-18c6b catalyzed the isomerization of 4a to 4b with
exceptional 23:1 E:Z stereoselectivity (t1/2 = 190 h, TOF =
absence of salts; changing conditions to include NaBArF
4
results in formation of regioisomer c in 79 to 96% yield and
36:1 to >90:1 E:Z selectivity (excepting substrate 12a). The
regioselectivity changes more than 900-fold in most cases.
While, in principle, one could imagine simply running the
salt-promoted reaction for short times to obtain the same
distribution of b isomer (and for long times to obtain the c
isomer), this is not possible in practice: the 2-18c6b/Na+
system produces b isomers with poor stereoselectivity (see
Figure 4C above). Similar product distributions favoring the
(E)-c isomer were obtained when LiBArF4 was used in place of
0.44 h−1). The addition of NaBArF led to a 4500-fold rate
4
enhancement (t1/2 = 0.042 h, TOF = 1800 h−1). The
stereoselectivity of 2-18c6b also changes in the presence of
NaBArF with 2-18c6b (Table S3), but for simplicity,
NaBArF : even at early times, (E)-4b is only moderately
4
subsequent studies focused only on the Na+ salt. The distinct
stereoselectivity of the two catalyst states enables production of
either of two olefin products with high regioselectivity and high
stereoselectivity, simply by addition of a Na+ salt. The
selectivity can also be switched in situ, if desired. Isomerization
of 4a by 2-18c6b alone resulted in 95% yield of 4b; addition of
4
favored (E:Z = 5:1), while 2-18c6b without salt additives
produced (E)-4b with E:Z ratios of 23:1 throughout the
reaction (Figure 4B/C). Aqua complex 3-18c6b is drastically
inhibited relative to 2-18c6b in the absence of salts (t1/2
=
2200 h, TOF = 0.031 h−1). Yet, surprisingly, 3-18c6b is only
slightly slower than water-free catalyst 2-18c6b in the presence
NaBArF to the mixture flipped the regioselectivity toward 4c
4
of NaBArF (t1/2 = 0.14 h, TOF = 510 h−1, Figure S21).
4
(94% yield after 24 h, Table S1). This result also confirms that
4b is a viable intermediate in the production of 4c.
The new 18-crown-6-based catalyst is superior to the
previously reported 15-crown-5-based catalyst in several facets:
2-18c6b isomerizes 4a up to 10 times faster; the commercially
The ester-functionalized arene 12a reacted more slowly than
other electron-deficient substrates, even in the presence of Na+.
Evidence for inhibition by ester coordination to the catalyst
was obtained in the reaction of a 1:1 mixture of ethyl acetate
and 4a. After 120 h at 50 °C, only 6% of (E)-4c isomer was
observed, with the dominant product being 4b (93%).
A broader range of 1-butene derivatives was examined next,
with the results summarized in Table 2. The aliphatic substrate
4-methyl-1-pentene (13a) could be transposed to either
internal regioisomer by cation-responsive catalyst 2-18c6b.
available salt NaBArF can be used; and enhanced water
4
tolerance is evident in the salt-promoted reactivity of 3-18c6b.
With the consideration that cation-responsive catalysis
produces different internal olefins, the ability of Na+ to alter
the activity and stereoselectivity of 2-18c6b was promising.
The reaction profile suggested that salt-free conditions might
produce a single stereoselective isomerization, with salt-
promoted conditions giving multiple isomerizations.
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Table 1. Cation-Responsive Isomerization of Butenyl
a
Arenes to Either Internal Isomer
a
Yield of internal isomers; remaining mass balance is starting terminal
olefin (see SI Section II for details).
Next, we turned to olefins containing Lewis bases, 5-hexen-
2-one (16a), methyl pentenoate (17a), and 4-methoxy-1-
butene (18a). Initial studies using catalyst 2-18c6b revealed
sluggish reactivity, even in the presence of NaBArF (Figure
4
S46−S48). We hypothesized that the Lewis basic groups on
the substrate were forming a stable chelate, preventing product
release and inhibiting catalysis. Thinking that a small amount
of water could act as a nonchelating ligand to facilitate product
release, we turned to the aqua complex 3-18c6b. Whereas <5%
c isomer was observed in each case with 2-18c6b/Na+,
switchable regioselectivity was observed with aqua catalyst 3-
18c6b/Na+. Table 2 shows that isomerization of ketone-
Figure 4. Isomerization of 4a (blue circles) to (E)-4b (dark orange
squares) to (Z)-4b (light orange pentagons) by Ir catalysts at 25 °C.
Summary of catalytic results (A), and NMR time courses of 2-18c6b
alone (B) and in the presence of NaBArF (C).
4
containing 16a gave 92% yield of 16b without NaBArF and
4
26% yield of 16c with NaBArF ; isomerization of ester-
4
Without salts, singly isomerized product 13b was obtained in
containing 17a gave 88% yield of 17b without NaBArF and
94% yield (13:1 E:Z); in the presence of NaBArF , the doubly
46% yield of 17c with NaBArF ; ether-containing 18a4 gave
4
4
isomerized product 13c was obtained in 75% yield (along with
some disubstituted terminal alkene 13d).10 Both allyl and vinyl
silyl ethers were accessible from the triisopropylsilyl (TIPS)-
ether-protected alcohol (14a) using 2-18c6b with the
appropriate salt (Table 2). In this case, the Z isomer of 14c
88% yield of 18b without salts and 46% yield of 18c with
NaBArF . Control reactions showed no isomerization when
4
several of the substrates described above were treated with
NaBArF or LiBArF in the absence of any iridium catalyst.
4
Computational4 Studies of Relative Energetics of
Olefin Isomers. DFT computations were carried out to
examine the relative stability of regioisomers of the 1-butene
derivatives examined in the catalytic studies. Compared to
MP245−48/aug-cc-pVDZ,49 previously used to examine long-
chain functionalized olefins,50 B3LYP/6-311++G(d,p) more
accurately reflected experimental values and was therefore
utilized here (with DCE solvent modeled as a polarizable
continuum; see SI Section III for full details).51,52
was the major product in the presence of NaBArF .43,44 The
4
representative boronic ester 15a underwent isomerization with
2-18c6 to give 76% yield of 15b (16:1 E:Z). In the presence of
Na+, 15c is formed in 64% yield with excellent stereoselectivity
(16:1 E:Z, Table 2). Olefins with terminal acetal, trimethylsilyl,
or acetoxy groups converted to distributions favoring the b
isomer, both with and without salts (Table S2). The salt-free
conditions still gave the b isomer in excellent E selectivity.
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Table 2. Cation-Responsive Isomerization of 1-Butenes to
a
Either 2- or 3-Butenes
Figure 5. Thermodynamic distributions of 1-butenes from DFT
(B3LYP/6-311G++(d,p) at 50 °C, and 1,2-dichloroethane continuum
solvent model). The disubstituted terminal olefin derived from 4-
methyl-1-butene is shown in purple.
tions. Given the important role of steric interactions in
directing selectivity in isomerization,17,53 we propose that the
2-selective isomerization stems from a catalyst state featuring a
tetradentate (κ4) binding mode with one crown ether oxygen
bound during turnover, while the 3-selective isomerization
takes place from a catalyst state with a tridentate (κ3) binding
mode. Spectroscopic monitoring is consistent with a change in
resting state, with sharp signals for 2-18c6b present in salt-free
conditions and only very broad resonances detectable in the
presence of NaBArF . Substrates containing Lewis basic
4
functional groups are proposed to form chelates, filling the
vacant coordination site apparent in several intermediates of
Scheme 1, slowing product release and inhibiting catalysis.
The cation-responsive reactivity of the 18-crown-6-based
catalysts was predicted by earlier binding affinity studies of
model complexes.36,37 Previous binding affinity studies of
model nickel and iridium complexes revealed that 15-crown-5-
based pincer-crown ether complexes bind Li+ stronger than
Na+, aligning with the high Li+ specificity in rate-tunable
allylbenzene isomerization with 2-15c5.36,37 Previous studies
of structurally related model pincer complexes containing an
18-crown-6 ether group revealed a similar binding affinity for
Li+ (Ka = 34 M−1) compared to 15-crown-5-based complexes
(Ka = 76 M−1).36 This led to the successful prediction of
similar rates of olefin isomerization for 2-15c5b (TOF = 160
a
Yield of internal isomers; remaining mass balance is starting terminal
b
c
olefin (see SI Section II for details). No Z isomer detected. 5 mol %
d
e
NaBArF . 2.5 mol % catalyst. 2.5 mol % catalyst, 5 mol % NaBArF .
4
4
Figure 5 summarizes the computational results. The 1-
butene derivatives can be organized into two categories based
on their computed thermodynamic distributions of re-
gioisomers. Seven substrates had a distribution where the c
regioisomer was the lowest energy species, while three
substrates showed a thermodynamic preference for the b
regioisomer (Figure 5).
h−1) or 2-18c6b (TOF = 190 h−1) in the presence of LiBArF .
3. DISCUSSION
4
Proposed Mechanism of Olefin Isomerization and
Influence of Crown Ether Size. The new complex 2-18c6 is
not only a rare catalyst capable of a single positional
isomerization with exceptional E stereoselectivity but also a
unique example of a single catalyst that can be modified
through noncovalent interactions to produce either of two
internal isomers. Scheme 1 proposes a mechanism that
accounts for the distinct cation-controlled product distribu-
We also successfully predicted that 2-18c6 would have much
higher Na+-promoted activity than 2-15c5, based on the huge
difference in binding affinity in model complexes with aza-15-
crown-5 (Ka(Na+) = 19 M−1) and aza-18-crown-6 (Ka(Na+) =
15000 M−1) groups.37 Indeed, the new catalyst 2-18c6b (TOF
= 1800 h−1) isomerizes olefins ca. 300 times faster than 2-
15c5b (TOF = 5.7 h−1) in the presence of NaBArF . The
4
distinct reactivity of the salt adduct interplays with
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Scheme 1. Proposed Mechanism of Cation-Responsive Isomerization by Iridium Pincer-Crown Ether Catalysts
thermodynamics of the olefinic products to explain the
observed switchable behavior.
Understanding Regioselectivity Control. Switchable
regioselectivity is accessed across a wide range of butenes. In
the absence of salts, the catalyst 2-18c6b (or 3-18c6b)
facilitates a single isomerization of the double bond to the first
internal position, producing the b isomer in high yield and with
high regioselectivity and high stereoselectivity (favoring the E
isomer). The ratio of b:c regioisomers without salts often
exceeded 40:1. In the presence of NaBArF , the doubly
4
isomerized product is formed instead, also in high yield and
favoring the E isomer (b:c ratio typically beyond 1:8).
The crux of the switchable reactivity is the thermodynamic
landscape of olefin isomerization. In a comparison of the
computed regioisomer distributions with the experimental
outcomes under different conditions, it is clear that the
catalytic reactions in the presence of NaBArF generate the
4
most thermodynamically favored isomer (the “thermodynamic
product”). Conversely, the regio- and stereoselectivity of
reactions catalyzed by 2-18c6b in the absence of salts are
consistent with a high degree of kinetic control: the
thermodynamic product is not obtained, and instead a specific
and less stable isomer is produced. Thus, the switchable
selectivity stems from a cation-induced change between kinetic
control and thermodynamic control.
Figure 6. Simplified reaction coordinate diagrams for olefin
isomerization depicting the case where cation-controlled selectivity
is possible (A) and the case where thermodynamic limitations prevent
access to the c isomer (B).
The general features of the reaction coordinate diagrams
depicted in Figure 6A are shared by each substrate for which
switchable regioselectivity was observed. A “stair-step” stability
pattern is apparent on the basis of computed thermodynamic
parameters (see Figure 5 above): the starting terminal olefin a
being the least stable, isomer b being intermediate, and isomer
c being the thermodynamic product (due to π-conjugation or
hyperconjugation). The experimental studies show that, in the
absence of a salt, the kinetic barrier to convert a to b is
surmountable, but further isomerization to regioisomer c is not
observed (even with prolonged reaction times). The kinetic
product b is thus obtained, and 2-18c6b alone produces high
yields of this isomer with exquisite regioselectivity (and
stereoselectivity; see below). If instead the reaction is
kinetic barriers when using 2-18c6b. Better control over
regioselectivity was obtained with the aqua catalyst 3-18c6b.
The lack of cation-responsive reactivity of butenes with silyl,
acetyl, and ketal substituents can be explained by a change in
thermodynamic landscape: DFT calculations reveal that isomer
c is not the most stable species in these cases, with b being
favored instead. As shown in Figure 6B, the same regioisomer
will be produced regardless of whether the reaction is under
kinetic or thermodynamic control.
Rationalizing Unique Stereoselectivity in Each Cata-
lytic State. The pincer-crown ether catalyst 2-18c6b is one of
a select few catalysts capable of facilitating a single positional
isomerization with exceptional stereoselectivity for the E-
isomer.11,13,14,16,53,54 The high stereoselectivity of pincer-
performed with NaBArF , the barriers for all isomerizations
4
are reduced dramatically, and the reaction proceeds under
thermodynamic control to the most stable regioisomer. Even
with NaBArF , butenes containing Lewis basic groups faced
4
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crown ether catalysts in the absence of salts (E:Z ratios often
exceeding 15:1 even at 50 °C) was not previously recognized
because prior studies focused on isomerization of allylben-
zene:34 the E isomer of the product β-methylstyrene is highly
favored thermodynamically (E:Z ca. 20:1 at 25 °C), obscuring
any kinetic selectivity of the catalyst.55 The butene-containing
substrates, in contrast, have only a moderate thermodynamic
preference for the E isomer (ca. E:Z 4:1).54,56
The high stereoselectivity of 2-18c6b in the absence of salts
is proposed to originate from steric congestion of the crown
ether (Scheme 1). Computational studies have shown that the
Ir−O bond trans to phenyl is easiest to dissociate, which can
open up an alkene binding site.41 Without salts, we
hypothesize that one crown ether oxygen remains bound to
the Ir center during catalysis, providing additional steric
pressure that can influence selectivity by favoring the transition
state that forms the E isomer and disfavoring internal olefin
binding.
distinct. Here, we propose that the change in selectivity stems
from a structural change in the primary coordination sphere via
changes in ether ligand hemilability. When one ether remains
bound to the catalyst, the kinetic product is obtained; when no
ethers are bound to the catalyst, the thermodynamic product is
instead produced. Thus, modifications that alter ligand lability
or the primary coordination sphere may be expected to have
strong impacts on reaction selectivity in other catalysts as well.
Changing the primary coordination sphere via external
additives in order to control selectivity is notably distinct from
the prevailing approach to noncovalent catalyst modification.
Typically, additives interact with the supporting ligand (or two
supporting ligands interact with each other) to change the
overall steric profile or the ligand bite angle, without altering
the coordination number. This strategy has been highly
effective in tuning the linear/branched regioselectivity in
alkene hydroformylation,23,33 including examples of cation−
crown interactions tuning ligand bite angle.26,27,30 Because the
macrocycle in pincer-crown ether ligands is directly bound to
the catalyst, cation binding influences the primary coordination
sphere, which we propose to be essential for controlling
regioselectivity and stereoselectivity between two sterically
similar internal olefin isomers.
The stereoselectivity of 2-18c6b changes upon the addition
of NaBArF , leading to thermodynamic distributions of E and Z
4
isomers. For example, isomerization of 4a with 2-18c6b/
NaBArF produces 4b with selectivity close to the expected
4
thermodynamic distribution (E:Z = 4:1). As shown in Scheme
1, we propose that Na+ binding leads to cleavage of both Ir−O
bonds and release of steric pressure near the active site. This is
consistent with prior studies of model complexes showing
negligible cation binding by pincer-crown ether complexes
with tetradentate (κ4) or pentadentate (κ5) binding modes but
strong binding when tridentate (κ3) binding modes with no
bound ether oxygens are adopted.36 The mechanistic model of
Scheme 1 helps explain why shortening the reaction time of 2-
18c6b/Na+-catalyzed reactions would not produce the same
outcome as the salt-free system: each catalytic state has a distinct
structure and thus distinct stereoselectivity.
Design Principles for Non-Covalent Catalyst Mod-
ification. The prevailing paradigm in catalyst design involves
synthetic tuning of supporting ligands. In this work, we explore
a complementary strategy based on noncovalent modification
of the catalyst structure.20−25 There are no prior examples of a
single catalyst that can produce either of two internal olefin
isomers through the influence of noncovalent interactions, to
our knowledge. Thus, our mechanistic insight can provide
some initial design principles for how cation-controlled
selectivity in isomerization reactions may be achieved.
4. CONCLUSIONS
A single cation-responsive pincer-crown ether iridium catalyst
can produce either of two internal isomers using appropriate
external additives. In the absence of salts, 2-18c6b isomerizes
1-butene derivatives to the corresponding 2-butene (allyl
derivatives) with exceptional regio- and stereoselectivity.
Under otherwise identical conditions, but in the presence of
NaBArF , the doubly isomerized 3-butenes (vinyl derivatives)
4
are produced. Combined experimental and computational
studies guided the development of a model that explains the
selectivity outcomes. Two distinct catalytic state are accessed:
one (salt-free) that exhibits high kinetic selectivity for a single
E-selective isomerization and another (salt-activated) that
exhibits thermodynamic selectivity. Cation−macrocycle inter-
actions are proposed to change the pincer ligand binding
mode, resulting in distinct activity and selectivity traits. The
selective generation of individual internal olefin isomers from a
single catalyst offers promise for the diversification of olefins
relevant to the fragrance, pharmaceutical, and other industries.
A catalyst should be able to access two states, each with
unique reactivity. One state must provide high selectivity for a
kinetic product; the other state can provide selectivity for a
different kinetic product or for the thermodynamic product.
Knowledge of the thermodynamic landscape of the isomers
under consideration is helpful in this regard: in our case,
computational investigations rapidly identified systems with
appropriate relative thermodynamics. An additional require-
ment is that the two states must not interconvert rapidly. In
this case, strong cation−macrocycle interactions maintain the
second state.
ASSOCIATED CONTENT
■
sı
* Supporting Information
The Supporting Information is available free of charge at
https://pubs.acs.org/doi/10.1021/jacs.0c11601.
Experimental details and characterization data (PDF)
Coordinates of optimized geometries of iridium
complexes (XYZ)
Coordinates of optimized geometries of olefins (XYZ)
Steric factors have proven essential in controlling the
selectivity in positional olefin isomerization. Ruthenium
catalysts exhibit distinct selectivity based on the cyclo-
pentadienyl substitution pattern,57,58 for example, and the
regioselectivity in cobalt-catalyzed isomerization is dramatically
impacted by the steric profile of bi- and tridentate phosphine-
based ligands.14,59 These observations suggest that the two
catalyst states in a responsive system should be sterically
Accession Codes
CCDC 2057901 and 2057906−2057912 contain the supple-
mentary crystallographic data for this paper. These data can be
obtained free of charge via www.ccdc.cam.ac.uk/data_request/
cif, or by emailing data_request@ccdc.cam.ac.uk, or by
contacting The Cambridge Crystallographic Data Centre, 12
Union Road, Cambridge CB2 1EZ, UK; fax: +44 1223 336033.
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Article
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AUTHOR INFORMATION
Corresponding Author
Alexander J. M. Miller − Department of Chemistry, University
of North Carolina at Chapel Hill, Chapel Hill, North
Carolina 27599−3290, United States; orcid.org/0000-
0001-9390-3951; Email: ajmm@email.unc.edu
■
Authors
Andrew M. Camp − Department of Chemistry, University of
North Carolina at Chapel Hill, Chapel Hill, North Carolina
27599−3290, United States
Matthew R. Kita − Department of Chemistry, University of
North Carolina at Chapel Hill, Chapel Hill, North Carolina
27599−3290, United States
P. Thomas Blackburn − Department of Chemistry, University
of North Carolina at Chapel Hill, Chapel Hill, North
Carolina 27599−3290, United States
Henry M. Dodge − Department of Chemistry, University of
North Carolina at Chapel Hill, Chapel Hill, North Carolina
27599−3290, United States
Chun-Hsing Chen − Department of Chemistry, University of
North Carolina at Chapel Hill, Chapel Hill, North Carolina
27599−3290, United States; orcid.org/0000-0003-
0150-9557
(16) Yu, X.; Zhao, H.; Li, P.; Koh, M. J. Iron-Catalyzed Tunable and
Site-Selective Olefin Transposition. J. Am. Chem. Soc. 2020, 142,
18223−18230.
Complete contact information is available at:
https://pubs.acs.org/10.1021/jacs.0c11601
(17) Chen, C.; Dugan, T. R.; Brennessel, W. W.; Weix, D. J.;
Holland, P. L. Z-Selective Alkene Isomerization by High-Spin
Cobalt(II) Complexes. J. Am. Chem. Soc. 2014, 136, 945−955.
Notes
The authors declare no competing financial interest.
̈
(18) Schmidt, A.; Nodling, A. R.; Hilt, G. An Alternative Mechanism
for the Cobalt-Catalyzed Isomerization of Terminal Alkenes to (Z)-2-
Alkenes. Angew. Chem., Int. Ed. 2015, 54, 801−804.
ACKNOWLEDGMENTS
■
(19) Becica, J.; Glaze, O. D.; Wozniak, D. I.; Dobereiner, G. E.
Selective Isomerization of Terminal Alkenes to (Z)-2-Alkenes
Catalyzed by an Air-Stable Molybdenum(0) Complex. Organo-
metallics 2018, 37, 482−490.
The work was supported by the National Science Foundation
under CAREER award Grant No. CHE-1553802. The authors
thank M. ter Horst for assistance with NMR spectroscopy
experiments and B. Ehrmann for assistance in the RISE
Catalysis Center within the Department of Chemistry Mass
Spectrometry Core Laboratory. The NMR spectroscopy was
supported by the National Science Foundation under Grant
No. CHE-1828183 and Grant No. CHE-0922858. The mass
spectrometry was supported by the National Science
Foundation under Grant No. CHE-1726291.
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