Terminal Alkyne Coupling Reactions through a Ring: Mechanistic Insights and Regiochemical Switching

Article abstract of DOI:10.1002/anie.201807028

The mechanism and selectivity of terminal alkyne coupling reactions promoted by rhodium(I) complexes of NHC-based CNC pincer ligands have been investigated. Synthetic and kinetic experiments support E- and gem-enyne formation through a common reaction seq

Full text of DOI:10.1002/anie.201807028

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Accepted Article
Title: Terminal alkyne coupling reactions through a ring: mechanistic
insights and regiochemical switching
Authors: Caroline M Storey, Matthew R Gyton, Rhiann E Andrew, and
Adrian B Chaplin
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To be cited as: Angew. Chem. Int. Ed. 10.1002/anie.201807028
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10.1002/anie.201807028
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COMMUNICATION
Terminal alkyne coupling reactions through a ring: mechanistic
insights and regiochemical switching
Caroline M. Storey,[a] Matthew R. Gyton,[a] Rhiann E. Andrew,[a] and Adrian B. Chaplin*[a]
Abstract: The mechanism and selectivity of terminal alkyne coupling
reactions promoted by Rh(I) complexes of NHC-based CNC pincer
ligands have been investigated. Synthetic and kinetic experiments
support E- and gem-enyne formation through a common reaction
sequence involving hydrometallation and rate determining C–C bond
reductive elimination. The latter is significantly affected by the ligand
topology: employment of a macrocyclic variant enforces exclusive
head-to-head coupling, contrasting the high selectivity for head-to-
tail coupling observed for the corresponding acyclic pincer.
The transition metal catalysed dimerisation of terminal alkynes
into conjugated enynes is an attractive, atom economical
method for the preparation of versatile organic building blocks
from readily accessible starting materials.[1,2] These reactions
involve the formal addition of the C(sp)-H bond of one alkyne
across the C≡C bond of the other, a process which can in
principle result in three different regio- or stereochemical
isomers: gem-, E-, and Z-enynes. With the additional possibility
for the substrates to be consumed through competing metal
catalysed reaction pathways
butatrienes, arenes or other polyenes
–
for instance leading to
the widespread
–
application of terminal alkyne coupling reactions in organic
synthesis rests on the development of catalysts that can enforce
high reaction control.[1,3] Despite the evaluation of a variety of
transition metal complexes this remains a largely unfulfilled
aspiration, with few catalysts capable of producing single enyne
isomers with sufficiently high selectivity.[4]
Scheme 1. Selected complexes and proposed mechanistic pathways for the
rhodium pincer catalysed formation of gem- and E-enynes from terminal
alkynes (ArF = 3,5-(CF3)2C6H3).
Motivated by these precedents and as part of our research
exploring the organometallic chemistry of NHC-based pincer
ligands,[10,11] we set about evaluating the use of rhodium
complexes containing neutral lutidine-based CNC ligands in
terminal alkyne coupling reactions. In particular, we were
interested in ascertaining the capacity of macrocyclic variants for
imparting additional reaction control. To this end, we herein
describe our work contrasting the reactions of Rh(I)-ethylene
Building on early landmarks,[5] rhodium-based catalysts are
of notable contemporary interest.[6–9] Recent examples bearing
anionic pincer ligands, in particular, show promising activity and
product fidelity. For instance, Rh(CNC) complex A has been
shown to be a highly selective pre-catalyst for the production of
a range of gem-enynes (1 mol%, 80 oC),[6] while Rh(PNP)
complex B principally affords E-enynes under similar conditions
(1 mol%, 100 oC).[7] Although closely related Rh(PNP) and
Rh(PCP) systems demonstrate reduced selectivity, they
predominantly give mixtures of only gem- and E-enynes.[7,8] As
previously asserted by Ozerov,[8] these observations implicate a
common hydrometallation-reductive elimination mechanism for
the aforementioned rhodium pincers; a scheme which bifurcates
on coordination of the second alkyne to afford either “head-to-tail”
(gem-) or “head-to-head” (E-) coupled products (i.e. II→III vs.
II→V in Scheme 1). The formation of Z-enynes instead typically
evokes vinylidene intermediates.[1]
complexes [Rh(CNC-Me)(C2H4)][BArF ]
1
and [Rh(CNC-
4
12)(C2H4)][BArF ] 2 with a bulky terminal alkyne (Scheme 1; R =
4
3,5-tBu2C6H3 ≡ Ar’). These novel and appreciably air-sensitive
complexes were synthesised, employing reactions of the
corresponding Cu(I) transfer agents [Cu(CNC)][BArF ] with
4
[Rh(C2H4)2Cl]2,[11] and fully characterised in solution and the
solid-state (see ESI and Figure 1). Reinforcing the electronic
similarities of the CNC-Me and CNC-12 ligands evident from
these data, the corresponding Rh(I)-carbonyl derivatives
[Rh(CNC-Me)(CO)][BArF ] 3 and [Rh(CNC-12)(CO)][BArF ] 4
4
4
have directly comparable carbonyl stretching frequencies (ν(CO)
= 1980, 3; 1978 cm-1, 4).[12]
[a]
C. M. Storey, Dr. M. R. Gyton, Dr. R. E. Andrew, Dr. A. B. Chaplin
Department of Chemistry, University of Warwick
Gibbet Hill Road, Coventry CV4 7AL, United Kingdom.
E-mail: a.b.chaplin@warwick.ac.uk
Under comparably milder conditions to those employed for A
and B, 1 was found to be an effective and selective pre-catalyst
for the homocoupling of HC≡CAr’ in CD2Cl2, affording the gem-
product Ar’C≡CC(CH2)Ar’ exclusively until alkyne conversion
reached >90% (5 mol%, t1/2 = 4.2 h, 25 °C, Scheme 2). At this
Homepage: http://go.warwick.ac.uk/abchaplin
Supporting information for this article is given via a link at the end of
the document.
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10.1002/anie.201807028
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These observations can be reconciled by a hydrometallation
mechanism for the HC≡CAr’ homocoupling with the resting state
IV (viz. 6) and turnover limiting C–C bond reductive elimination
(i.e. IV→I in Scheme 1). Consistent with this suggestion, a
kinetic analysis using the more active
1 indicated the
homocoupling reaction is zero-order in the alkyne substrate and
first order in 1 (Scheme 2). Working within our conjecture, the
activation barrier for the reductive elimination step was also
determined through measurement of the reaction’s temperature
dependence, affording ΔG‡ (298 K) = 93 ± 3 kJmol-1 (ΔH‡ = 97 ±
1 kJmol-1, ΔS‡ = 15 ± 5 JK-1mol-1, Scheme 2).
Figure 1. Solid-state structures of 1 and 2. Thermal ellipsoids drawn at 50%
probability level; anions and most hydrogen atoms omitted for clarity. Selected
data: 1, Rh1–Cnt(C2,C3), 2.033(3) Å; C2–C3, 1.373(4) Å; Rh1–N101, 2.116(2)
Å; Rh1–C109, 2.037(2) Å; Rh1–C115, 2.042(2) Å; Py–Rh–C=C twist, 16.0(2)º;
2, Rh1–Cnt(C2,C3), 1.996(3) Å; C2–C3, 1.363(5) Å; Rh1–N101, 2.116(2) Å;
Rh1–C109, 2.042(3) Å; Rh1–C115, 2.061(3) Å; Py–Rh–C=C twist, 31.7(2)º.[13]
Paralleling the formation of 6, reaction of 2 with a 2.1 equiv.
of HC≡CAr’ in CD2Cl2 led to rapid and quantitative formation of
Rh(III) gem-alkenyl complex 7, which was subsequently isolated
and fully characterised (Scheme 2, Figure 2). Presumably as a
consequence of the confined metal coordination sphere evident
in the solid-state, 7 is appreciably dynamic in solution on the
NMR time-scale (500 MHz, see ESI). The spectroscopic
characteristics nevertheless corroborate the structure of 7 in the
solution phase. For instance the presence of germinal 1H
resonances at δ 5.57 and 5.76 alongside doublets in the 13C
point, nearing complete consumption of the alkyne, there was
evidence for subsequent metal-catalysed reaction of the
enyne,[14] however, Ar’C≡CC(CH2)Ar’ could be readily isolated in
practically useful yield (73%) by quenching the reaction with
carbon monoxide at high alkyne conversion: sequestering the
catalyst as 3. Alternative use of [Rh(CNC-Me)(SOMe2)][BArF ] 5
4
1
NMR spectrum at δ 85.0 (RhC≡C, JRhC = 72 Hz) and 157.7
as the pre-catalyst maintained the exclusive gem-selectivity
observed for 1, but was an order of magnitude slower under
equivalent conditions (5 mol%, 25 °C), presumably due to
reversible binding of dimethyl sulfoxide. Whilst use of 5 is
detrimental to catalytic activity it advantageously facilitated in
situ investigation of the organometallic intermediates involved by
NMR spectroscopy and ESI-MS. In this way, a single and
persistent species was identified and, following additional
1
(RhC(CH2)Ar’, JRhC = 27 Hz). While the intricacies of the
spectroscopic data diverge, the most meaningful difference
between 6 and 7 is the significantly enhanced stability of the
latter, macrocyclic variant. Reminiscent of active-metal-template
methods used in the construction of interlocked molecules,[16]
7
does however undergo C–C bond reductive elimination through
the annulus of the bound CNC-12 ligand when heated in the
higher boiling point solvent 1,2-C2D4Cl2. Curiously, the resulting
mechanically entrapped hydrocarbon product is not the gem-
enyne Ar’C≡CC(CH2)Ar’, expected for a single reaction step and
through extrapolation of the of reactivity established for 1 and 5,
but instead the alternative E-regioisomer E-Ar’C≡CCH=CHAr’
(Scheme 2).[17] The associated Rh(I) adduct 8 is formed
quantitatively and was isolated from solution and
comprehensively characterised, including in the solid-state using
single crystal X-ray diffraction (see ESI and Figure 2).
interrogation
under
conditions
more
amenable
to
characterisation (33 mol%, 5 °C), assigned as Rh(III) gem-
alkenyl complex 6 (Scheme 2, cf. IV in Scheme 1). Notable
spectroscopic features of 6 include C1 symmetry, two 18H tBu
1
resonances, geminal alkene H resonances at δ 3.21 and 4.79
1
and 13C resonances at δ 101.9 (RhC≡C, JRhC = 55 Hz) and
1
153.8 (RhC(CH2)Ar’, JRhC = 38 Hz) that display large 103Rh
coupling.[15] Isolation of 6 from solution was encumbered by
facile reductive elimination of Ar’C≡CC(CH2)Ar’.
Scheme 2. Reactions of 1 and 2 with HC≡CAr’. [BArF4]– counter anions omitted for clarity.
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10.1002/anie.201807028
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terminal alkyne coupling reactions can be controlled and, more
generally, showcase an unconventional approach for tuning the
reactivity of pincer ligands.[18] As
a
proof of concept
demonstration of how this knowledge could be applied, the
orthogonal selectivity of acyclic 1 and macrocyclic 2 can be
exploited to prepare both PhC≡CC(CH2)Ph (catalytically) and E-
PhC≡CCH=CHPh (stoichiometrically) from HC≡CPh in high yield
(Scheme 3, see ESI for full details). Our future work is focused
on exploring the application of these lutidine-based CNC ligands
in catalysis, supramolecular and organometallic chemistry.
Figure 2. Solid-state structures of 7 and 8. Thermal ellipsoids drawn at 50%
and 30% probability level, respectively; anions, minor disordered components
(1×tBu group in 7; 1×Ar’ and 1×CH2CH2 group in 8), solvent molecules and
most hydrogen atoms omitted for clarity. 7: Rh1–C2, 1.940(5) Å; C2–C3,
1.204(8) Å; Rh1–C2–C3, 176.6(5)º; Rh1–C4, 1.983(5) Å; C4–C5, 1.310(8) Å;
Rh1–C4–C5, 140.1(4)º; C2–Rh1–C4, 96.6(2)º; Rh1–C6, 2.435(5) Å; Rh1–
N101, 2.228(5) Å; Rh1–C109, 2.066(5) Å; Rh1–C115, 2.075(6) Å; 8: Rh1–
Cnt(C2,C3), 1.981(3) Å; C2–C3, 1.255(4) Å; C2–C4, 1.425(4) Å; C4–C5,
1.338(4) Å; C2–C4–C5, 124.7(3)º; Rh1–N101, 2.105(2) Å; Rh1–C109,
2.052(3) Å; Rh1–C115, 2.042(3) Å; Py–Rh–C≡C twist, 38.7(2)º.[13]
Scheme 3. Preparation of PhC≡CC(CH2)Ph and E-PhC≡CCH=CHPh
Acknowledgements
We thank the European Research Council (ERC, grant
agreement 637313; C.M.S., M.R.G., A.B.C.), University of
Warwick (R.E.A.), and Royal Society (UF100592, UF150675,
A.B.C.) for financial support. Crystallographic (1, 3, 8) and high-
resolution mass-spectrometry data were collected using
instruments purchased through support from Advantage West
Midlands and the European Regional Development Fund.
The formation of
8 from 7 necessitates a multi-step
mechanism starting with β-H abstraction and terminating with
reductive elimination from a Rh(III) E-alkenyl alkynyl (viz. VI in
Scheme 1). Moreover on the basis of a labelling experiment,
involving heating 7 in the presence of excess DC≡CAr’ and
resulting in significant D incorporation into both positions of the
enyne core, exchange and reversible C(sp)–H activation of both
alkyne components must occur, viz. IV⇌III⇌II(⇌I)⇌V⇌VI→8
(Scheme 1 and 2). No intermediates were observed when
following the conversion of 7 into 8 in situ by 1H NMR
spectroscopy, with the reaction following ideal first order kinetics
across a wide temperature range (328 – 348 K). On the basis of
these data, we assign reductive elimination step as the rate-
determining step: with an associated barrier of ΔG‡ (298 K) =
106 ± 3 kJmol-1 (ΔH‡ = 119 ± 1 kJmol-1, ΔS‡ = 44 ± 4 JK-1mol-1).
Crystallographic data for 2, 5, 7 and [Cu(CNC-12)][BArF ] were
4
collected using an instrument that received funding from the
ERC under the European Union’s Horizon 2020 research and
innovation programme (grant agreement No 637313).
Keywords: Enynes • C–C coupling • pincer ligands •
macrocyclic ligands • rhodium
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ΔG‡ (298 K) = 13 ± 6 kJmol-1, triggering a switch in product
selectivity. These observations provide new insight into how
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COMMUNICATION
Caroline M. Storey, Matthew R.
Gyton, Rhiann E. Andrew, and
Adrian B. Chaplin*
Terminal alkyne coupling reactions
promoted by Rh(I) complexes of
NHC-based CNC pincer ligands
have been studied. Employment of
a macrocyclic variant enforces a
change in selectivity, promoting
head-to-head at the expense of
head-to-tail dimerisation.
Page No. – Page No.
Terminal alkyne coupling
reactions through a ring:
mechanistic insights and
regiochemical switching
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