Introducing a podand motif to alkyne metathesis catalyst design: A highly active multidentate molybdenum(VI) catalyst that resists alkyne polymerization

Article abstract of DOI:10.1002/anie.201007559

Podand prevents polymers: The molybdenum(VI) propylidyne catalyst 1 with a podand triphenolamine ligand shows high activity in the metathesis of a variety of alkyne substrates, including heterocycles that contain donor moieties. With one substrate-binding site blocked by the multidentate ligand, the undesired polymerization of small alkynes that occurs with non-podand-ligand complex 2 is completely inhibited. Copyright

Full text of DOI:10.1002/anie.201007559

DOI: 10.1002/anie.201007559
Alkyne Metathesis
Introducing A Podand Motif to Alkyne Metathesis Catalyst Design:
A Highly Active Multidentate Molybdenum(VI) Catalyst that Resists
Alkyne Polymerization**
Kuthanapillil Jyothish and Wei Zhang*
There has been significantly growing interest in recent years
in the transition-metal-catalyzed metathesis of alkenes and
alkynes.[1] The synthetic potential of alkyne metathesis,
however, is much less explored though they have shown
enormous potential in the preparation arylene ethynylene
polymers,[2] macrocycles,[3] and in natural product synthe-
sis.[1c,4] Typically, the metal alkylidyne catalysts for alkyne
metathesis contain a tungsten or molybdenum–carbon triple
bond and alkoxide/amide ligands,[1–5] and their catalytic
activity can be tuned by judicious ligand design.[1–9]
Coordination of small molecules, and in particular
2-butyne (a common metathesis byproduct), to the hexava-
lent molybdenum alkylidyne complex is known to be an
interfering reaction and leads to undesired alkyne polymer-
ization (through the ring-expansion mechanism, which
requires two open substrate-binding sites) as well as non-
productive reaction pathways.[10] Polyhedral oligomeric sil-
sesquioxane (POSS) and silica are the only reported ligands
to date that can overcome this long-standing problem.[9a,11]
However, the siloxane-based approach lacks tunability in the
catalyst structure, thus making it difficult to study the
structure–activity relationship of the catalyst and tune its
activity. Our present study is aimed at the design of a
multidentate organic ligand that can block one substrate-
binding site of the molybdenum center to inhibit the
undesired alkyne polymerization while also keeping the
structural tunability for introducing customizable electron-
withdrawing substituents to improve both the metathesis
activity and functional group tolerance.
Scheme 1. Synthesis of the multidentate ligand L1 and the generation
ꢀ
ꢀ
of the alkyne metathesis catalysts [L1Mo( CEt)] (1) and [(L2)3Mo(
ꢀ
CEt)] (2) from the molybdenum(VI) precursor [(3,5-C6H3(tBu)N)3Mo(
CEt)]. Conditions: a) NaBH(OAc)3, NH4OAc, THF, RT, 69%; b) LiI,
quinoline, 1708C, 87%.
starting from the corresponding methyl-protected salicylal-
dehyde followed by reductive amination and deprotection
(Scheme 1). A crystal of the complex 1 was obtained from a
1:1 mixture of the molybdenum(VI) propylidyne precursor
and L1 using a solvent system comprising nitrobenzene and
carbon tetrachloride.[13] The single-crystal X-ray structure
analysis showed a phenoxide-bridged dimer of complex 1 with
an octahedral coordination geometry around each metal
center (Figure 1). Interestingly, the trigonal-pyramidal geom-
etry of the triphenolamine ligand enables the coordination of
the central nitrogen to molybdenum, thus efficiently blocking
one open binding site of the complex. These interesting
features are anticipated to make the catalyst 1 resistant to the
interfering alkyne polymerization, and the strong chelating
effect of the multidentate ligand should significantly enhance
the catalyst stability and its activity.
Taking advantage of the favorable trigonal pyramid
geometry of trisubstituted amines,[12] we designed the triphe-
nolamine ligand L1 (Scheme 1) that would allow the effective
coordination of the three phenol moieties to molybdenum,
with the three methylene units blocking one substrate-binding
site of the metal center. The synthesis of the multidentate
triphenolamine ligand (L1) was achieved in good yield
[*] Dr. K. Jyothish, Prof. Dr. W. Zhang
Department of Chemistry and Biochemistry, University of Colorado
Boulder, CO 80309 (USA)
Fax: (+1)303-492-5894
E-mail: wei.zhang@colorado.edu
[**] We thank Prof. Cort Pierpoint for help with X-ray structure analysis,
Dr. Richard Shoemaker for assistance with NMR spectroscopy, and
the University of Colorado for the funding support through the
innovative seed grant program.
ꢀ
Figure 1. Crystal structure of the dimeric complex [{L1Mo CEt}2]
shown in two different orientations. Ellipsoids set at 50% probability;
hydrogen atoms omitted for clarity.
Supporting information for this article is available on the WWW
under http://dx.doi.org/10.1002/anie.201007559.
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The solvent compatibility of
1
was tested with
observed for these model reactions, even with catalyst
loadings of as low as 3 mol% (based on Mo). Successful
metathesis of 1,4-diynes opens many new possibilities for
preparing cross-conjugated polymeric or cyclic molecules.
Given the high functional group tolerance and metathesis
activity of 1, the idea of utilizing the multidentate structural
feature to inhibit small alkyne polymerization was tested with
2-butyne, the metathesis byproduct of propynyl substrates.
Indeed, as hypothesized, even in the presence of a large
excess of 2-butyne (> 100 equiv), use of 1 did not lead to any
polymerization (Supporting Information, Figure S5) even
after 24 h. However, the catalyst generated from the corre-
sponding monodentate analogue 4-nitrophenol (2), showed a
broad peak around d = 1.7–2.0 ppm (Supporting Information,
Figure S5) within 1 h after exposure to 2-butyne, thus
indicating significant polymerization had occurred (Table 2,
entry 1).
Previously, the high catalytic activity of 2 was reported,
and it has been successfully employed in the synthesis of
conjugated polymers and shape-persistent macrocycles with
high efficiency.[1d,2b,3a–c] A comparison of the metathesis
activity of 1 versus 2 showed that our newly designed
multidentate molybdenum catalyst has even higher catalytic
activity and broader substrate scope. In particular, the
metathesis of substrates containing donor moieties, such as
pyridine substrates (Table 2, entries 2,3), failed when 2 was
4-propynylanisole as the substrate in a series of solvents
(carbon tetrachloride, chloroform, toluene, chlorobenzene,
1,2-dichlorobenzene, 1,2,4-trichlorobenzene, and THF, in a
closed system). The catalyst is metathesis-active in all of the
above solvents (52–70% conversion), and the highest con-
1
version is observed in carbon tetrachloride. H NMR spec-
troscopy experiments using 1,4-dimethoxybenzene as an
internal standard showed the quantitative displacement of
the precursor ligands (Supporting Information, Figure S2)
with L1 and the in situ generation of 1 in the solution phase.
Furthermore, the 13C NMR analysis of the trisamido molyb-
denum(VI) propylidyne precursor before and after mixing
with L1 showed a significant deshielding effect; the chemical
shift of the carbyne carbon bonded to the metal moved from
d = 302.6 ppm[14] to d = 322.6 ppm, further indicating the
displacement of anilide ligands on the molybdenum(VI)
propylidyne precursor with L1 (Supporting Information,
Figure S3, S4). Furthermore, 15N NMR experiments by using
a 15N-labeled sample of L1 gave insight into the coordination
behavior of the central nitrogen atom to molybdenum. The
signal observed at d = 44.8 ppm for the nitrogen in the free
ligand L1 shifted significantly to d = 69.0 ppm upon mixing
with the catalyst precursor, which indicates the coordination
of the L1 nitrogen to the metal center to form the multi-
dentate metal complex (Supporting Information, Figure S3,
S4).
Table 1 summarizes some model
experiments that use the catalyst
Table 1: Homodimerization, ring-closing alkyne metathesis, and cross-metathesis reactions of propynyl
substrates and 1,4-diynes.[a]
system 1 generated in situ and with
carbon tetrachloride as the solvent.
The scope of the metathesis activity
was probed with various substrates:
1) containing electron donating/
withdrawing substituents; 2) heter-
ocyclic molecules; 3) the ring-clos-
ing alkyne metathesis (RCAM)
of diynes to cycloalkyne; and
4) 1,4-diynes that are generally con-
sidered as difficult substrates, pre-
sumably owing to the formation of
undesired stable metal–diyne che-
lates.[15] Interestingly, 1 was found to
be compatible with all the different
substrates tested, and even chal-
lenging examples containing nitro
and aldehyde functional groups that
are known to shut down the activity
of some highly active alkyne meta-
thesis catalysts.[7a,b,16,17] All the
metathesis products were obtained
in good to excellent yields under
ambient conditions.[18] In particular,
catalyst 1 gave the highest yield to
date[6a,17] for the metathesis of p-
nitro-substituted propynyl benzene,
thus substantiating the high cata-
lytic activity of 1. Half-lives of less
Entry Substrate
T
t
Product
Yield
[%]
[8C] [h]
1
2
3
4
5
RT
RT
40
4
4
7
87[b]
80[b]
71[b]
55[b]
74[b]
40 12
40
40
4
4
6
7
93[b]
40
40
4
7
60[c]
44
8
(45)[b,d]
[a] 3 Mol% catalyst loading for all entries. [b] In a closed system (solvent CCl4), and the solution exposed
to vacuum 4–5 times during the reaction to remove the metathesis byproduct 2-butyne. [c] No removal
of the byproduct alkyne, equilibrium conditions. [d] The number in parenthesis indicates the isolated
than
1 hour
were
generally monoanisole silane.
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Table 2: Comparison of the metathesis activity of 1 versus 2.[a]
In summary, compared to
alkyne metathesis catalysts with
monodentate ligands, the high cata-
lytic activity and robustness of 1 can
be attributed to two major factors:
1) stronger complexation offered by
the multidentate ligand (entropy-
favored) in comparison to a mono-
dentate ligand, making the catalyst
more robust and elongating its life
time; and 2) spatial blocking of one
substrate-binding site of the molyb-
denum alkylidyne complex, com-
pletely inhibiting undesired alkyne
polymerization, and also greatly
minimizing non-productive sub-
strate binding, thus enabling the
efficient metathesis of heterocycles
that contain donor moieties. The
high functional group tolerance, fast
reaction rate, and high stability are
three great advantages of catalyst 1.
More importantly, the strategy of
utilizing multidentate ligands opens
Entry Substrate
T
t [h] Product
Yield of Yield of
[8C]
1 [%][b] 2 [%][b]
1
RT 24
–
40
2
3
70
70
3
3
61
20
–
–
2/
4
30
95
84
22[c]
[a] 3 Mol% catalyst loading for entries 1, 2, 4; 7 mol% for entry 3. [b] Yields in a closed system (solvent:
CCl4); – no reaction. [c] Reaction times: 1: 2 h, 2: 22 h.
used, even with high catalyst loadings (10–15 mol%). In
contrast, the same substrates were successfully metathesized
by 1 (Supporting Information, Figure S8). To the best of our
knowledge, o-propynylpyridine is a very tough substrate, and
its homodimerization by alkyne metathesis has not yet been
reported. Using 1, catalytic metathesis (Table 2, entry 3) was
accomplished, thus further indicating the superior activity of
catalyst 1. The precipitation-driven cyclooligomerization[3c] of
many new possibilities for the design of highly efficient,
robust alkyne metathesis catalysts. Currently, the structure–
activity relationship of this novel class of catalysts and their
synthetic applications toward well-defined molecular archi-
tectures are being investigated in our laboratories and will be
reported in due course.
diyne monomer (Table 2, entry 4) by alkyne metathesis Experimental Section
General procedure for metathesis experiments: The ligand and the
further substantiated the high activity of 1; even with
3 mol% catalyst loading, the reaction is complete within 2 h
at 308C with a yield of 95% (Supporting Information,
Figure S9). In contrast, for 2, with 10 mol% catalyst loading,
the same transformation took 22 h to give a yield of 84%.[3c] It
was also observed that reducing the catalyst loading to
3 mol% significantly lowered the reaction conversion when 2
was used (Supporting Information, Figure S10).
The multidentate catalyst 1 is also much more stable than
2. The metathesis activity of these two catalysts at different
time intervals after their in situ generation (in the absence of
substrates) was compared, with 4-chloropropynylbenzene as
the substrate. Complex 1 showed a comparable activity
(<10% decrease) even after 24 h and retained appreciable
catalytic activity for several days, whereas 2 showed activity
only within the first few hours. It was also observed that
adding the substrate in the very beginning to the pre-
generated catalyst solution for 2 led to longer catalyst
lifetimes. This result indicates an intermolecular decomposi-
tion pathway[19] for 2, either through ligand loss by cleavage of
precursor were premixed in dry carbon tetrachloride for 20 min to
generate the catalyst in situ. The substrate was then added and the
stirring was continued with regular monitoring of the reaction by
NMR spectroscopy. During the reaction, the solution was exposed to
vacuum (about 4 or 5 times, 20 s each time) to remove the metathesis
byproduct 2-butyne. Loss of solvent during the application of vacuum
was compensated by adding fresh solvent each time. For purification
of the metathesis reaction products (Table 1, entries 1–6, 8; Table 2,
entries 2 and 3), the solvent was removed with a rotary evaporator
and the residue obtained was subjected to column chromatography
over silica gel. For entry 4, the reaction mixture was filtered before
the filtrate was concentrated and subjected to column chromatog-
raphy over silica gel. For full details, see the Supporting Information.
Received: December 1, 2010
Revised: January 7, 2011
Published online: March 10, 2011
Keywords: alkylidynes · alkyne metathesis ·
.
cyclooligomerization · homogeneous catalysis · podand ligands
À
the labile Mo O bond or by catalyst dimerization. The
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Angew. Chem. Int. Ed. 2011, 50, 3435 –3438
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Communications
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[13] The crystal was obtained from the solvent mixure after the
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