"canopy Catalysts" for Alkyne Metathesis: Molybdenum Alkylidyne Complexes with a Tripodal Ligand Framework

Article abstract of DOI:10.1021/jacs.0c04742

A new family of structurally well-defined molybdenum alkylidyne catalysts for alkyne metathesis, which is distinguished by a tripodal trisilanolate ligand architecture, is presented. Complexes of type 1 combine the virtues of previous generations of silanolate-based catalysts with a significantly improved functional group tolerance. They are easy to prepare on scale; the modularity of the ligand synthesis allows the steric and electronic properties to be fine-tuned and hence the application profile of the catalysts to be optimized. This opportunity is manifested in the development of catalyst 1f, which is as reactive as the best ancestors but exhibits an unrivaled scope. The new catalysts work well in the presence of unprotected alcohols and various other protic groups. The chelate effect entails even a certain stability toward water, which marks a big leap forward in metal alkylidyne chemistry in general. At the same time, they tolerate many donor sites, including basic nitrogen and numerous heterocycles. This aspect is substantiated by applications to polyfunctional (natural) products. A combined spectroscopic, crystallographic, and computational study provides insights into structure and electronic character of complexes of type 1. Particularly informative are a density functional theory (DFT)-based chemical shift tensor analysis of the alkylidyne carbon atom and 95Mo NMR spectroscopy; this analytical tool had been rarely used in organometallic chemistry before but turns out to be a sensitive probe that deserves more attention. The data show that the podand ligands render a Mo-alkylidyne a priori more electrophilic than analogous monodentate triarylsilanols; proper ligand tuning, however, allows the Lewis acidity as well as the steric demand about the central atom to be adjusted to the point that excellent performance of the catalyst is ensured.

Full text of DOI:10.1021/jacs.0c04742

Subscriber access provided by Uppsala universitetsbibliotek
Article
“Canopy Catalysts” for Alkyne Metathesis: Molybdenum
Alkylidyne Complexes with a Tripodal Ligand Framework
Julius Hillenbrand, Markus Leutzsch, Ektoras Yiannakas, Christopher P.
Gordon, Christian Wille, Nils Nöthling, Christophe Copéret, and Alois Fürstner
J. Am. Chem. Soc., Just Accepted Manuscript • DOI: 10.1021/jacs.0c04742 • Publication Date (Web): 28 May 2020
Downloaded from pubs.acs.org on May 28, 2020
Just Accepted
“Just Accepted” manuscripts have been peer-reviewed and accepted for publication. They are posted
online prior to technical editing, formatting for publication and author proofing. The American Chemical
Society provides “Just Accepted” as a service to the research community to expedite the dissemination
of scientific material as soon as possible after acceptance. “Just Accepted” manuscripts appear in
full in PDF format accompanied by an HTML abstract. “Just Accepted” manuscripts have been fully
peer reviewed, but should not be considered the official version of record. They are citable by the
Digital Object Identifier (DOI®). “Just Accepted” is an optional service offered to authors. Therefore,
the “Just Accepted” Web site may not include all articles that will be published in the journal. After
a manuscript is technically edited and formatted, it will be removed from the “Just Accepted” Web
site and published as an ASAP article. Note that technical editing may introduce minor changes
to the manuscript text and/or graphics which could affect content, and all legal disclaimers and
ethical guidelines that apply to the journal pertain. ACS cannot be held responsible for errors or
consequences arising from the use of information contained in these “Just Accepted” manuscripts.
is published by the American Chemical Society. 1155 Sixteenth Street N.W.,
Washington, DC 20036
Published by American Chemical Society. Copyright © American Chemical Society.
However, no copyright claim is made to original U.S. Government works, or works
produced by employees of any Commonwealth realm Crown government in the
course of their duties.

Page 1 of 44
Journal of the American Chemical Society
1
2
3
4
5
6
“Canopy Catalysts” for Alkyne Metathesis: Molybdenum Alkylidyne Complexes with a Tripodal
Ligand Framework
7
8
9
Julius Hillenbrand,ǂ Markus Leutzsch,ǂ Ektoras Yiannakas,ǂ Christopher P. Gordon,¤ Christian Wille,ǂ
Nils Nöthling,ǂ Christophe Copéret,¤ and Alois Fürstnerǂ*
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
ǂ
Max-Planck-Institut für Kohlenforschung, 45470 Mülheim/Ruhr, Germany
¤
Department of Chemistry and Applied Biosciences, ETH Zürich, Vladimir-Prelog-Weg 1-5, 8093
Zürich, Switzerland
ABSTRACT: A new family of structurally well-defined molybdenum alkylidyne catalysts for alkyne
metathesis is presented, which is distinguished by a tripodal trisilanolate ligand architecture.
Complexes of type 1 combine the virtues of previous generations of silanolate-based catalysts with a
significantly improved functional group tolerance. They are easy to prepare on scale; the modularity
of the ligand synthesis allows the steric and electronic properties to be fine-tuned and hence the
application profile of the catalysts to be optimized. This opportunity is manifested in the development
of catalyst 1f, which is as reactive as the best ancestors but exhibits an unrivaled scope. The new
catalysts work well in the presence of unprotected alcohols and various other protic groups. The
chelate effect entails even a certain stability towards water, which marks a big leap forward in metal
alkylidyne chemistry in general. At the same time, they tolerate many donor sites, including basic
nitrogen and numerous heterocycles. This aspect is substantiated by applications to polyfunctional
(natural) products. A combined spectroscopic, crystallographic and computational study provides
insights into structure and electronic character of complexes of type 1. Particularly informative are a
DFT-based chemical shift tensor analysis of the alkylidyne carbon atom as well as 95Mo NMR
spectroscopy; this analytical tool had been rarely used in organometallic chemistry before but turns
out to be a sensitive probe that deserves more attention. The data show that the podand ligands
render a Mo-alkylidyne a priori more electrophilic than analogous monodentate triarylsilanols; proper
ligand tuning, however, allows the Lewis acidity as well as the steric demand about the central atom
to be adjusted to the point that excellent performance of the catalyst is ensured.
1
ACS Paragon Plus Environment

Journal of the American Chemical Society
Page 2 of 44
1
2
3
4
5
Introduction
In a recent Communication we disclosed complex 1a as the prototype of a new generation of
molybdenum alkylidyne complexes, termed “canopy catalysts” for alkyne metathesis because of their
distinguishing tripodal silanolate ligand framework (Figure 1).1 Shortly after our paper had been
published, the Lee group presented its work that had incidentally pursued the same ligand design.2
6
7
8
9
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
Ar
OMe
Mo
Ph3SiO
Ph3SiO
OSiPh3
Ph
Ph
Mo Si
O
Ph
Ph
2a
b
Ar = p (MeO)C6H4

O
Si
Ar = 2,6-(Me)2C6H3
O
Ph
Ph
Si
Ar
1a
OSiPh3
N
Ph3SiO
Ph3SiO
Mo
N
R3Si
Mo
R3Si
O
Mo
O
2.
[
(phen)]
Figure 1. Prototype of the “canopy catalysts” and the parent triphenylsilanolate complexes;
modulation of the donor properties of a silanolate ligand caused by the facile bending and stretching
of the MoOSi angle
Even though the focus of these two parallel investigations had been somewhat different, both reached
the conclusion that such complexes are more than just a “tethered” variant of catalyst 2a carrying
triphenylsilanolate ligands, which had set new standards in the field of alkyne metathesis when it was
introduced by our group a decade ago.3,4,5,6 Outlined below is a comprehensive study into this new
family of “canopy catalysts”, including the optimization of their synthesis, a first ligand tuning exercise,
structural investigations, a portrayal of their electronic nature, and new insights into the elementary
steps of the catalytic cycle. Most importantly, a focused evaluation of the catalytic performance
revealed an unrivaled stability towards numerous basic as well as protic sites, including unprotected
alcohols and even moisture. Overall, this investigation shows that 1a and relatives bear great potential
and might well mark a new milestone in the evolution of alkyne metathesis at large.7,8,9,10
2
ACS Paragon Plus Environment

Page 3 of 44
Journal of the American Chemical Society
1
2
3
4
5
Results and Discussion
Design Principles. Complexes 2 and derived bench-stable adducts such as [2(phen)] (phen = 1,10-
phenanthroline) owe their excellent application profile to the synergy between the operative
molybdenum alkylidyne unit11 and the ancillary silanolate ligands.3-5 Silanolates are weaker - and -
donors than ordinary alkoxides12 and have “adaptive” ligand properties (Figure 1):3-5 bending and
stretching of a MoOSi hinge comes with thermal motion at almost no cost. Any such change of the
bond angle, however, alters the hybridization of oxygen and hence the degree of -donation, which,
in turn, gently modulates the energy of the catalyst’s frontier orbitals. For this very property, 2 is able
to meet the opposing electronic optima of the elementary steps passed through during the catalytic
cycle: substrate binding and metallacycle formation are favored by a more Lewis-acidic center,
whereas the cycloreversion step and extrusion of the product as the chemically inverse operations
have the exact opposite electronic demand.3-5,13,14 At the same time, (triaryl)silanolates15 are
sufficiently bulky to preclude bimolecular decomposition and/or competing associative pathways
resulting in alkyne polymerization from occurring. For the longer OSi and SiC bonds, however, the
“bulk” is sufficiently remote from the molybdenum center not to impede substrate binding or product
dissociation; only for very hindered alkynes is the size of the silanolates critical.16 In that silanolates
lower the barriers of all elementary steps and, at the same time, protect the catalyst, they render the
overall reaction efficient on electronic and steric grounds.3-7
6
7
8
9
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
The tempered Lewis-acidity that 2a and relatives draw from the metal/ligand cooperativity also
accounts for a remarkable compatibility with functional groups.3-5 Numerous applications to complex
and/or sensitive target molecules bear ample witness of this fact;17,18 an instructive example is shown
in Scheme 1. Even certain protic groups are tolerated,19,20 although important limitations still remain.
This particular problem is challenging: the polarization of a Schrock alkylidyne renders the C-atom of
the [MCR] unit innately nucleophilic and basic and hence potentially prone to degradation in a protic
environment.11,21 Ligand exchange, however, is equally obstructive: any in situ replacement of the
silanolates of 2 jeopardizes the virtues of the catalyst and ultimately entails loss of activity. This may
explain why 2 usually fails when primary alcohols or related protic sites are present; the comparison
shown in Scheme 1 illustrates the “paradox”.
3
ACS Paragon Plus Environment

Journal of the American Chemical Society
Page 4 of 44
1
2
3
4
5
6
7
Scheme 1. Current State of the Art: Triarylsilanolate Catalysts Tolerate Diverse Functionality and
Complex Settings but Fail with Simple Unhindered Alcoholsa
8
9
a
2
cat.
BnO
O
O
MS 5Å, RT
OMe
Cl
O
O
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
toluene
87%
O
BnO
O
O
O
OMe
Cl
O
O
O
PMBO
O
O
TBSO
TBSO
PMBO
OMe
O
O
RO
O
OTBS
OR
OMe
TBSO
R = PMB
2
cat.
OH
no reaction
MS 5Å, RT
toluene
a complex 2 was released in situ from the corresponding ate-complex chosen as precatalyst, cf. ref. 17c
Scheme 2. Previous Attempts to Prepare Molybdenum Alkylidyne Complexes with a Podand Ligand
Architecture22,23
Et
N
6a
4
5
or
N
Mo
N
6b-d
or
3
Et
mixtures
Mo
N
O
O
O
NO2
O2N
7
NO2
HO
OH
OH
Ph2Si
X
R
SiPh2
Ph2Si
OH
X
HO
X
Z
R
HO
4
R
HO
OH
SiPh2
OH
Ph2Si
6a
Z = N, X = NO2, R = H
SiPh2
+
6b
6c
6d
Z = (NMe) , X = NO2, R = Me
Si
R
Z = SiMe, X = H, R = Me
Z = CH, X = NO2, R = iPr
5
R = Me, Ph
4
ACS Paragon Plus Environment

Page 5 of 44
Journal of the American Chemical Society
1
2
3
4
5
6
7
8
9
Under the premise that ligand exchange is detrimental, it seemed reasonable to assume that a chelate
structure might improve stability vis-à-vis alcohols and other protic substrates. Our first attempt to
reduce this plan to practice met with only partial success (Scheme 2).22 Specifically, the trisilanol
ligands 4 and 5 were designed but failed to afford distinct tripodal alkylidyne complexes on reaction
with precatalyst 3. Rather, they lead to partial cross-linking with formation of ill-defined mixtures,
which nonetheless show good activity and, as a matter of fact, an improved functional group tolerance
compared to 2.22 It was with the help of these two-component systems that certain substrates
containing primary –OH groups could be metathesized for the first time in appreciable yields.22
(Partial) cross-linking also seems to plague an alternative ligand scaffold of type 6 comprised of
tethered phenol units:23,24,25 the only fully characterized podand complex 7 derived from 3 and 6a
proved inactive, whereas the composition of those mixtures that are catalytically competent is
unclear.23 In consideration thereof, we were prompted to re-assess the design and came up with 1 as
the prototype of a new generation of catalysts for alkyne metathesis:1,26 In a formal sense, the three
Ph3SiO- groups of the parent complex 2 are tied together via an additional phenyl ring that forms the
basal plane of a podand ligand framework. In contrast to 4 and 5, the backbone of this new type of
tridentate ligand (11) contains only sp2-hybridized C-atoms, which reduces the degrees of
conformational freedom and should render the formation of well-defined tripodal complexes more
favorable; however, this comes at the cost of increased rigidity, even though we had hoped that the
conformationally flexible MoOSi angle would partly compensate the perceived stiffness of
complexes of type 1. It is important to note that each alkyne metathesis catalyst must be able to
accommodate different geometries, that is the tetrahedral ligand environment of the alkylidyne and a
trigonal-bipyramidal extreme at the stage of the metallacyclobutadiene intermediate formed upon
[2+2] cycloaddition.7-10 Provided that this essential geometric boundary condition is met, the
modularity of the design should allow the properties of this new catalyst family to be fine-tuned.
Ligand Synthesis and Variation. The preparation of the parent ligand 11a starts off with the
cyclocondensation of 2-bromoacetophenone to afford tribromide 8a (Scheme 3).27,28 This reaction was
originally performed with triflic acid at elevated temperature but was later found to be much higher
yielding upon gentle release of HCl from SiCl4 and EtOH;29 under these conditions, the yield of 8a
increased from 55% to 90% on a 20 g scale. Exhaustive metal/halogen exchange with excess tBuLi in
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
5
ACS Paragon Plus Environment

Journal of the American Chemical Society
Page 6 of 44
1
2
3
4
5
6
7
8
9
Et2O followed by quenching of the resulting tri-organolithium intermediate with Ph2Si(OMe)2 works
nicely (75%, 4 g scale), provided that the metalation step is performed at very low temperature
(125°C).30 The final hydrolysis proceeds quantitatively on treatment of 9a with aqueous HCl (5 g
scale). Trisilanol 11a is thus available in multigram quantity in three high-yielding steps.
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
Scheme 3. Ligand Synthesisa
Br
O
X
a) or b)
Ph
Ph
R
R
R
Ph
Ph
Br
C
HO
OH
Si
Y
R
Br
Si
X
Y
C
X
g)
c) or d)
R
Br
Si
Y
R
X
X
8
C
HO
12
Ph
Ph
X
X
a
X = H, R = Ph
X = F, R = Ph
9
Y = OMe
Y = H
b
c
d
e
e)
10
11
X = H, R = (MeO)C6H4
X = H, R = Me
f)
Y = OH
X = H, R = iPr
a Reagents and conditions: (a) SiCl4, EtOH, 0°C  RT, 90% (X = H, 20 g scale); (b) TfOH, 130°C, 55% (X =
F); (c) tBuLi, Et2O, R2Si(OMe)2, 125°C  RT, 75% (9a), 86% (9b), 12% (9c); (d) tBuLi, Et2O, R2SiH(Cl),
125°C  RT, 91% (10d), 81% (10e); (e) aq. HCl, 0°C  RT, quant. (11a, 5 g scale), 78% (11b), quant.
(11c); (f) mCPBA, 94% (11d in CH2Cl2), 81-87% (11e, in THF); (g) tBuLi, Et2O, benzophenone, 125°C 
RT, 78% (2 g scale)
Because this route is modular, it provides ready access to analogues as necessary for catalyst screening
and optimization. To this end, compound 11b28 bearing a fluorine substituent on the three arenes
forming the fence was prepared in good yield. Additional compounds were made to study the influence
of the substituents on silicon: quenching of the tri-organolithium species derived from 8a with
(MeOC6H4)2Si(OMe)2 followed by hydrolysis gave 11c. Although this reaction was less clean,31
a
sufficient amount was secured (ca. 400 mg) to study the properties of this particular ligand. For the
preparation of 11d,e with two aliphatic substituents on silicon, it was best to use R2Si(H)Cl (R = Me, iPr)
as the electrophilic partner; oxidative cleavage of the SiH bond in 10 with mCPBA furnished the
desired compounds. Even though silanols are privileged ligands for molybdenum alkylidynes,3-7 we also
6
ACS Paragon Plus Environment

Page 7 of 44
Journal of the American Chemical Society
1
2
3
4
5
6
prepared the carbinol analogue 12 for comparison by lithiation of 8a followed by a benzophenone
quench (Scheme 3).26
7
8
9
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
Figure 2. Structure of compound 11e in the solid state (only one of the two independent molecules in
the unit cell is shown); hydrogen atoms except for the –OH protons are not shown for clarity; the red
lines indicate hydrogen bonds
Figure 3. Structure of compound 12 in the solid state; co-crystallized CH2Cl2 and hydrogen atoms
(except for the –OH protons) are not shown for clarity; the red lines indicate hydrogen bonds
7
ACS Paragon Plus Environment

Journal of the American Chemical Society
Page 8 of 44
1
2
3
4
5
6
7
8
9
In the solid state, the trisilanol ligands 11a,1 11b,28 11c,28 and 11e (Figure 2) invariably adopt a
conformation in which the three Si-OH groups are “upward/inward”-oriented as a consequence of a
cyclic array of hydrogen bonds between the individual –Si-OH units. This favorable approximate C3-
symmetry, as necessary for the formation of the targeted podand complexes, is maintained in solution
as evident from the NMR spectra. The situation is very different for the carbinol analogue 12 (Figure
3): only one pair of reciprocal H-bonds connects only two of the alcohol groups, whereas the third OH
is oriented to the opposite side of the basal plane. Although line broadening in the NMR spectra
indicates that the system is dynamic at RT, the “two-up/one-down” geometry is the average
conformation of 12 in solution that gets increasingly locked upon cooling (see the SI).
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
Preparation of the Podand Complexes and the Aggregation Issue. The parent complex 2a is formed
from the tribromoalkylidyne complex 13a by salt metathesis with Ph3SiOM (M = K, Na).1,3,4 However,
this method was not deemed ideal for the preparation of the podand complexes of type 1 for the
following reasons: (i) The conformation of the trisilanols 11 is perfect for the envisaged podand
complex formation; deprotonation almost certainly enforces an unfavorable change, since charge
repulsion destabilizes the “upward/inward” orientation of the SiO vectors held together in 11 by
hydrogen bonding; (ii) any such conformational change, however, increases the likelihood of cross
linking; the resulting ill-defined products cannot convert to the targeted podand complex since salt
metathesis is irreversible; a reduced yield of 1 is the likely consequence;32 (iii) the poor solubility of the
trisodium (potassium) salts of 11 in aprotic organic media is a handicap in practical terms.33
The use of the molybdenum complex 3 bearing moderately basic amide ligands would probably allow
these issues to be avoided; it has already been shown to undergo ligand exchange with our “first-
generation” trisilanole ligands 4 and 5 (see Scheme 2).22 Yet, we sought a more practical solution
because 3 is exceptionally sensitive, requiring rigorously anhydrous conditions and an Ar (not N2!)
atmosphere.34 A convenient alternative was found in complexes 14, which themselves are catalytically
inactive but fairly easy to make (Scheme 4): since tert-butoxy groups are more basic than a silanole, it
suffices to stir a solution of 11a and 14a in toluene at ambient temperature to achieve quantitative
ligand exchange; moreover the reaction is entropically favorable.35 The released tert-butanol can be
evaporated in high vacuum, which makes the isolation of the resulting bright-yellow and only
moderately air-sensitive complex [1a]2 straightforward. The analogous reaction of the “all-carbon”
8
ACS Paragon Plus Environment

Page 9 of 44
Journal of the American Chemical Society
1
2
3
4
5
6
7
8
9
analogue 12 did not afford a podand complex (Scheme 5). Rather, the peculiar conformation of the
ligand translates into the structure of the resulting complex 16: two tert-butoxide ligands of 14a were
replaced by 12, which acts as a bidentate rather than tridentate ligand; the third tert-alcohol unit is
dangling and fails to substitute the remaining tert-butoxide even at elevated temperature (see the SI).
Complex 16 showed only marginal activity in the test reaction chosen to benchmark the new catalysts
(see below); however, it is reminiscent of a catalyst for applications in material science that had been
deliberately designed to exhibit a tempered character.36,37
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
Scheme 4. Preparation of the Catalystsa
Ar
Ar
Mo
14
Ar
a)
b)
OtBu
tBuO
Mo(CO)6
Mo Mo
Br
O
Mo
O
Br
Br
tBuO
tBuO
OtBu
tBuO
OtBu
Ar
15b
13
a
b
Ar = p-(MeO)C6H4
Ar = 2,6-(Me)2C6H3
OMe
OMe
Ar
Ar
Mo Si
Ar
O
Ar
O
Ar
Ar
Ar
Ar
Mo Si
O
O
c)
d)
Si
Si
14a
O
O
X
X
Si
Si
Ar
Ar
Ar
Ar
2
X
X
1
]
[
2
1
X
X
e)
a
b
c
X = H, Ar = Ph
OMe
X = F, Ar = Ph
X = H, Ar = (MeO)C6H4
Ph
N
O
Ph
Mo
Si
Ph
Ph
O
Si
O
Ph
Ph
Si
1a
[
MeCN]
a Reagents and conditions: (a) see ref. 4; (b) NaOtBu, THF, 83%; (c) 11, toluene, 95% ([1a]2), 50% ([1b]2,
76% ([1c]2); (d) toluene, 60°C, see Text; (e) MeCN, quant. (NMR), see Text
9
ACS Paragon Plus Environment

Journal of the American Chemical Society
Page 10 of 44
1
2
3
4
5
Scheme 5. The Carbinol Variant
OMe
6
7
8
9
Ph
O
Ph
Mo
O
12
14a
O
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
toluene
76%
Ph
Ph
Ph
Ph
HO
16
As previously described, the new podand complex [1a]2 is a supramolecular aggregate, which
dissociates quantitatively in toluene solution at 60°C to give the desired monomeric species 1a;1 once
formed, the monomer persists for extended periods of time (>> 7 d at RT (NMR); see the SI) and shows
excellent thermal stability (>> 12 h in [D8]-toluene at 60°C, see the SI). However, monomeric 1a reverts
to the dimeric aggregate [1a]2 upon evaporation of the solvent or on cooling; complexes 1b,c show the
same behavior. The acetonitrile adduct [1aMeCN], in contrast, remains monomeric in the solid state:
it was in this format that we were originally able to prove the podand ligand architecture about the
molybdenum alkylidyne unit by X-ray crystallography.1
Figure 4. Structure of complex of [2a]2 in the unit cell; all H-atoms except for the ortho-protons of the
benyzlidyne units are omitted for clarity; the red lines indicate the close interactions of these H-atoms
with neighboring phenyl rings of the silanolate ligands, indicative of CH/-interactions. The packing
reveals numerous intermolecular / and CH/ interactions between the two independent
molecules of this “dimeric” aggregate. Color code: Mo = yellow; O = red, Si = green, C = black
10
ACS Paragon Plus Environment

Page 11 of 44
Journal of the American Chemical Society
1
2
3
4
5
6
7
8
9
Although this aggregation in the solid state does not preclude alkyne metathesis from occurring,1 the
rather poor solubility of [1a]2 and the need to disassemble this aggregate via ligation and/or heating
are not ideal for applications in catalysis. Since crystals of [1]2 suitable for X-ray diffraction could not
be grown, indirect evidence had to guide our efforts to improve the design with the aim of avoiding
such complications. To this end, we revisited the structure of the parent complex 2a which is also a
dimeric aggregate in the solid state as well as in concentrated solution. Upon dilution, however, that
is under conditions typically used for ring closing alkyne metathesis (RCAM),38 [2a]2 fully dissociates to
the monomeric complex 2a (DOSY, see the SI). The X-ray structure (Figure 4)4 shows that the ortho-H
atoms of each benzylidyne unit of [2a]2 are engaged in tight CH/-interactions with neighboring
phenyl groups of the silanolate ligands; the latter, in turn, experience numerous intermolecular CH/-
and /-interactions39 with the phenyl rings of the second independent molecule in the unit cell. We
suppose that [1a]2 is the result of analogous non-covalent interactions:40 supramolecular aggregate
formation is hence likely a consequence of the multitude of fairly pre-organized arene rings in the first
ligand sphere about the molybdenum center.
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
Scheme 6.a
OMe
iPr
iPr
O
a)
b)
iPr
iPr
Mo Si
O
mixture
14a
Si
O
iPr
iPr
Si
1d
Me
Me
Me
Me
Ph
Me
Ph
O
O
c)
Me
d)
Me
Me
Ph
Ph
Mo
Si
Mo Si
O
O
O
14b
Si
Si
O
Me
Me
Ph
Ph
Si
Si
1f
1e
a
Reagents and conditions: (a) 11e, toluene, 99%; (b) 11d, toluene; (c) 11a, toluene, 65%; (d) 11d,
toluene, 84%
11
ACS Paragon Plus Environment

Journal of the American Chemical Society
Page 12 of 44
1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
Figure 5. Representation of the truncated structure of complex 1e in the solid state, in which the lateral
phenyl rings on silicon were removed to unveil the almost linear benzylidyne unit and the compressed
array of the core, which clearly deviates from an ideal tetrahedral geometry, see Text; hydrogen atoms
are omitted for clarity; for the full structure, see the SI
Figure 6. Structure of complex 1d in the solid state; hydrogen atoms are omitted for clarity
Based on this analysis, we envisaged two different ways to prevent supramolecular aggregate
formation. Under the proviso that the CH/-contact of the ortho-benzylidyne protons instigates a
network of tight intermolecular interactions, it may suffice to put ortho-substiuents on the benzylidyne
unit to break the contacts.41,42 The second conceivable design was the replacement of the phenyl
groups responsible for the intermolecular contacts altogether by appropriate alkyl substituents.15
12
ACS Paragon Plus Environment

Page 13 of 44
Journal of the American Chemical Society
1
2
3
4
5
6
7
8
9
In pursuit of these ideas, the 2,6-dimethylbenzylidyne complex 1e was prepared from 14b4,35 by the
route outlined above (Scheme 6). In line with our expectation, 1e is indeed monomeric in the solid
state (Figure 5) as well as in solution (DOSY, see the SI). The same is true for complexes 1d and 1f
carrying two aliphatic substituents on the silicon bridges: both of them are monomeric in solution (see
the SI), even though 1d retains the p-methoxybenzylidyne group. The X-ray structure of 1d (Figure 6)
contains two independent molecules in the unit cell but they do not entertain any short intermolecular
contacts between them (see the SI).
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
It is important to note that the reaction of the slimmest ligand 11d with 14b carrying an encumbered
2,6-dimethylbenzylidyne unit afforded the expected podand complex 1d together with a small amount
of an organometallic impurity, which also contains an alkylidyne (see the SI). The analogous reaction
of 11d with 14a bearing a p-methoxybenzylidyne, in contrast, furnished an ill-defined mixture which
was not analyzed any further (Scheme 6). These observations suggest that an adequate steric balance
between the size of the alkylidyne and the steric demand of the periphery is necessary to prevent
(partial) cross-linking from occurring.
Structural Aspects and Electronic Implications. The structures of 1d, 1e, and [1aMeCN]1 in the solid
state verify the tripodal silanolate ligand architecture capping the coordination site trans to the
alkylidyne. While the lengths of the Mo1C1 bonds (1.742(2) Å in 1e; 1.741(5) Å in 1d) fall into the
expected range,3,4 the alkylidyne units Mo1C1C2 of these complexes are almost linear, with bond
angles of 177.1(2)° and 176.2(4)°, respectively. For comparison, the alkylidyne of 2b has a bond angle
of only 171.4(2)°.4 Therefore we believe that the linearity in 1d and 1e is significant rather than
incidental.43 Such a linear array leads to optimal orbital overlap between the the Mo1C1 unit and the
arene and explains the rather short C1C2 bond (1.448(3) Å in 1e). In line with this notion, the
computed LUMO is indeed delocalized over the entire benzylidyne unit, with strong lobes on the 2,6-
dimethylphenyl ring (Figure 7).
The bond angles merit detailed consideration: For the canopy catalyst 1e, the MoOSi bond angles
are 156.2(1)°, 164.4(1)° and 170.6(2)°, whereas its monodentate cousin 2b shows 146.4(1)°, 154.1(1)°
and 169.4(1)°.4 The corresponding bond angles in 1d are fairly uniform (160.9(2)°, 161.3(2)°, 165(2)°)
but again more obtuse on average than that of 2b. As a consequence of this stretching in the periphery,
the ligand sphere about the Mo-center in 1d and 1e notably deviates from an ideal tetrahedral
13
ACS Paragon Plus Environment

Journal of the American Chemical Society
Page 14 of 44
1
2
3
4
5
6
7
8
9
geometry (Figure 5). This fact is also manifested in the significantly reduced C1Mo1O bond angles
(102.6(1)°, 103.2(1)°, 103.4(1)° in 1e; ideal tetrahedron: 109.47°): although the Mo-center resides
above the plane defined by the three O-atoms (0.42 Å), the elevation is smaller than in the parent
complex 2b (0.49 Å).
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
Figure 7. LUMO of Complex 1e
The Mo-atom of 1e is located 3.52 Å above the centroid of the phenyl ring that forms the basal plane
of the tripodal framework. At first sight, this situation resembles a largely electrostatic cation/-
interaction,39 but is likely more involved: the fact that the LUMO shows small but distinct lobes on the
basal phenyl group (Figure 7) indicates a weak but non-negligible through-space orbital interaction.44
This aspect is subject to further investigations.
95Mo NMR Study. The structures of 1d, 1e and [1aMeCN]1 in the solid state provide only a static
picture, but the observed geometric attributes of the complexes have important electronic
implications since they impact on the hydridization of the O-atoms and on the orbital overlap.
Therefore a more detailed investigation into the electronic character of the new catalysts in solution
seemed warranted.
As a spin 5/2 nucleus with low natural abundance (ca. 15.9%), low gyromagnetic ratio but a rather low
quadrupole moment, the 95Mo isotope has only rarely been used for analytical purposes in
organometallic chemistry.45 We are aware of a single investigation into molybdenum alkylidynes,46
14
ACS Paragon Plus Environment

Page 15 of 44
Journal of the American Chemical Society
1
2
3
4
5
6
7
8
9
which reports the Mo NMR shifts of [(Me3SiCH2)3MoCSiMe3] and [(Me3CCH2)3MoCCMe3],47 but
failed to record the signal of [(tBuO)3MoCPh]; all three complexes are catalytically incompetent.
Despite this only partly encouraging precedent, we found this technique very useful in the present
context. Good 95Mo NMR spectra of a representative set of complexes were obtained in [D8]-toluene
at 60°C: quadrupolar relaxation is slower at higher temperature and hence the lines are sharper;48 at
the same time, all complexes are monomeric in solution under these conditions. A well-resolved signal
at Mo = 79.6 ppm was recorded for [(tBuO)3MoCAr] (14a, Ar = p-MeOC6H4) (see the SI); this complex
is a close relative of [(tBuO)3MoCPh] that had defied detection in the only prior study.46 While 14a
itself is catalytically inactive, it serves as the starting point for the preparation of the canopy catalysts
(see Schemes 4 and 6).
95
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
OMe
Ph
Ph
O
Ph
Ph
Mo Si
O
Si
O
Ph
Ph
Si
1a
Me
Si
Me
Ph
Ph
O
Ph
Mo Si
O
O
Ph
Ph
Ph
Si
1e
550
500
450
95Mo (ppm)
400
350
Figure 8. 95Mo NMR spectra of the monomeric canopy complexes 1a and 1e differing only in the aryl
substituent on the alkylidyne; the spectra were recorded at 60°C
For the lack of pertinent literature data, it is currently impossible to construe the recorded shifts by
comparison with reference compounds. However, we are inclined to believe that the 95Mo shifts reflect
changes in the electronic character of these complexes quite closely: Figure 8 compares the spectra of
1a and 1e which carry the identical tripodal ligand but differ in the substitution of the benzylidyne.
15
ACS Paragon Plus Environment

Journal of the American Chemical Society
Page 16 of 44
1
2
3
4
5
6
7
8
9
Though quite remote, the change from the p-MeO group in 1a to the 2,6-dimethyl substitution pattern
in 1e entails notable deshielding. This fact proves that the Mo-alkylidyne is effectively coupled to the
-system of the arene: as a good donor substituent, the MeO- group imparts higher electron density
onto the Mo-center, which the spectral response seems to mirror.
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
Ar
Pr
i
Pr
i
O
Pr
Si
i
Si
Mo
O
Pr
i
O
Pr
i
i
Si
Pr
1d
Ar
Mo
Ph3SiO
Ph3SiO
OSiPh3
2a
Ar
R
R
O
R
Si
Mo
O
R
Si
O
R
R
Si
1c
R = (MeO)C6H4
Ar
O
Ph
Ph
Ph
Si
Mo
O
Ph
Si
O
Ph
Ph
Si
1a
Ar
Ph
Ph
O
Ph
Si
Mo
O
Ph
Si
O
F
Si
Ph
Ph
F
1b
F
500
450
400
95Mo (ppm)
350
300
95
Figure 9. Mo NMR spectra of different complexes (all in monomeric form) bearing the same aryl
substituent on the alkylidyne; all spectra were recorded at 60°C; Ar = p-MeOC6H4
To further probe this aspect, an additional series of complexes was analyzed. For the sake of direct
comparison, all of them carried the p-methoxybenzylidyne group (Figure 9) but differ in the silanolate
16
ACS Paragon Plus Environment

Page 17 of 44
Journal of the American Chemical Society
1
2
3
4
5
6
7
8
9
ligands; any electronic communication with the Mo-center is now mediated via the O-bridge. The
electron-withdrawing fluorides in 1b cause deshielding relative to the parent compound 1a, whereas
the two MeO- groups in 1c entail a small but significant shift to higher frequences. As expected, the
more drastic electronic change upon formal replacement of the aryl groups on silicon by more
electron-releasing iso-propyl substituents in 1d causes a more pronounced effect in the same
direction.49 Equally indicative is the finding that [(tBuO)3MoCAr] (14a, Ar = p-MeOC6H4) (Mo = 79.6
ppm) resonates at much higher field (see the SI), reflecting the fact that tertiary carbinol ligands are
better donors than silanols.12
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
The trend observed in the 95Mo spectra finds correspondence in the 13C as well as 29Si NMR shifts (Table
1); the only exception is the alkylidyne C-signal of 2a, but this complex has a different ligand set.
Although caution has to be exerted, it is tempting to see a qualitative correlation between these
spectral data with the electron density and hence Lewis-acidity of the metal center. Under this proviso,
the new complex 1a is more Lewis-acidic than the parent complex 2a, even though the rather obtuse
MoOSi angles would suggest otherwise. The influence of the bond angles seems to be outweighed
by the distortion of the first coordination sphere about the Mo(+6) center and the particular structural
features of the tripodal ligand framework.
Table 1. Relevant 95Mo, 29Si and 13C NMR shifts ([D8]-toluene, ppm) of molybdenum p-
methoxybenzylidyne complexes bearing different silanolate ligands
95Mo ()
29Si ()
13C ()
complex
1d
2a
1c
1a
1b
358
397
414
419
434
+10.2
8.0
9.1
9.9
9.8
303.3
300.5
309.3
310.4
311.4
Chemical Shift Tensor Analysis. The qualitative conclusion that the molybdenum alkylidyne unit of the
canopy catalyst 1e is slightly more Lewis acidic than that of its cousins 2b containing monodentate
triarylsilanolate ligands can be probed in greater detail by chemical shift tensor (CST) analysis of the
alkylidyne carbon atom.50 This approach is particularly appealing as the relation between 13C chemical
17
ACS Paragon Plus Environment

Journal of the American Chemical Society
Page 18 of 44
1
2
3
4
5
6
7
8
9
shift and molecular electronic structure of transition metal complexes is fairly well explored51 and has
been used to gain information on the electronic properties of metal alkylidynes and related
complexes.13,52
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
Figure 10. Three Relevant Orbital Couplings
Figure 11. CST Analysis of Complexes 1e and 2b
18
ACS Paragon Plus Environment

Page 19 of 44
Journal of the American Chemical Society
1
2
3
4
5
6
7
8
9
Chemical shift is an anisotropic property, which can be described by the three principal components
of the chemical shift tensor ((iso = (11 + 22 + 33)/3). The property calculated by ab initio methods is
the shielding tensor  (ii ≈ iso,ref - ii), which can be de-convoluted into diamagnetic and paramagnetic
terms ( = dia + para): while diamagnetic terms mainly arise from core orbitals and are hence quite
insensitive to the electronic environment, the paramagnetic contributions are sensitive to frontier
orbitals as they arise from the magnetically induced admixture of electronically excited states into the
electronic ground state via the angular momentum operator 퐿i. This relation between chemical shift
and molecular electronic structure makes chemical shift one of the few molecular descriptors that are
sensitive to the anisotropy of the electronic structure around a nucleus. In a pictorial view, strong
deshielding of a given nucleus occurs along a direction i if a high-lying occupied orbital on this nucleus
can be superimposed onto a low-lying vacant orbital on the same nucleus by rotation along the axis i.
Importantly, this deshielding is expected to increase for a decreasing energy gap between the involved
orbitals and is hence often indicative of reactive frontier orbitals (i.e. high-lying HOMO and/or low-
lying LUMO).
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
The three most relevant orbital couplings for a metal alkylidyne are schematically shown in
Figure 10: a previous investigation into metal alkylidynes showed that the -symmetric
orbitals contribute to deshielding by a magnetic coupling with the low-lying vacant *(M-C)
orbital, whereas the bonding (M-C) orbital causes deshielding by interaction with the vacant
*(M-C) orbital.13 The computed geometries of 2b and 1e were found to reproduce the crystal
structures well (for computational details, see the SI). The calculated isotropic shifts of 2b (C = 303
ppm) and its podand cousin 1e (C = 321 ppm) show good agreement with the experimental values
(307 ppm and 312 ppm, respectively). Consistent with experiment, the podand complex 1e is more
deshielded: interestingly, all three principal components of the shielding tensor make small
contributions that sum up to this net outcome (Figure 11). The larger deshielding of 1e suggests that
the *(Mo-C) orbital as the LUMO of 1e is lower-lying than that of 2b, which indicates a higher
electrophilicity of the canopy variant. This conclusion is consistent with the strongly delocalized
*(Mo-C) orbital (Figure 7): the lobes on the basal phenyl group of 1e suggest that this remote
substituent assists in lowering the energy of the LUMO.
19
ACS Paragon Plus Environment

Journal of the American Chemical Society
Page 20 of 44
1
2
3
4
5
6
7
8
9
Reactive Intermediates. It is not clear, a priori, whether the lower-lying LUMO of complexes of type 1
is an advantage for catalysis. As mentioned in the Introduction, it takes a well-balanced electrophilicity
management for a complex to become an efficient alkyne metathesis catalyst: a certain Lewis-acidity
is necessary for the [2+2] cycloaddition to happen,7-10,53 but if the electrophilic character is too
pronounced, the resulting metallacyclobutadiene is (over)stabilized and cycloreversion disfavored (not
to speak of the functional group tolerance that gets lost).13,14
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
Scheme 7. Discrete Intermediates Downstream the Molybdenum Alkylidynes
Ph
Ph
O
Ph
Ph
Mo Si
O
O
Si
> 95% (NMR)
Ph
Ph
Si
18
3-hexyne
?
Ph2
Si
Ph
Ph
O
3-hexyne
(5 equiv.)
O
Ph
Ph
Mo Si
O
O
3-hexyne
Si
O
Mo
1a
[D8]-toluene
Ph
Ph
Si
Ph
Si
23°C to -40°C
O
Si
Ph
Ph Ph
17
1a'
It was therefore deemed relevant to check whether the more electrophilic canopy catalysts 1 might
already enter the regime of (meta)stable metallacyclobutadienes. When 1a was treated with 3-hexyne
(5 equiv.) in [D8]-toluene in a temperature range between 40°C and +25°C a new complex 18 was
detected, which turned out to be a metallatetrahedrane rather than the expected
metallacyclobutadiene 17 (Scheme 7). The Lee group had been the first to observe the formation of
this unusual complex; because they managed to characterize 18 in detail by spectroscopic means and
even X-ray crystallography, we refrained from repeating the entire exercise.2 Our observations fully
confirm their lead finding; the fact that 18 is formed so easily implies that the metallatetrahedrane is
slightly more stable than (or at least isoenergetic with) the starting molybdenum alkylidyne and the
presumed metallacyclobutadiene 17 from which it is thought to derive according to theory.54 Since 1a
is a competent catalyst (see below), the question arises which role complex 18 plays in the catalytic
process. Based on probability arguments, metallatetrahedranes had been considered as possible on-
20
ACS Paragon Plus Environment

Page 21 of 44
Journal of the American Chemical Society
1
2
3
4
5
6
7
8
9
cycle intermediates,55 but computational studies and the isolation of a few unreactive representatives
advocated against this early assumption.56,57,58,59 Since then, it is generally believed that
metallatetrahedranes are unreactive sinks and/or a gateway to decomposition.60
The recorded NMR data (EXSY, ROESY) show beyond doubt that 18 exchanges with 3-hexyne as well
as with the propylidyne complex 1a’, which proves that formation of the metallatetrahedrane is
reversible (see the SI). However, the data gathered so far do not allow us to decide if 18 is a true on-
cycle intermediate or just an off-cycle reservoir, which would be more in line with previous views.56-58
If it is off the cycle, the high concentration of 18 in the mixture is a serious handicap because it keeps
much of the active molybdenum species away from doing its job. This question is highly relevant for
further optimization and hence subject to ongoing investigations in this laboratory.
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
Benchmarking of the Catalytic Activity. With a series of well-characterized tripodal alkylidyne
complexes of type 1 in hand, we were in the position to study how steric and electronic changes impact
on the catalytic properties. The homo-metathesis of 1-methoxy-4-(prop-1-yn-1-yl)benzene (19) to
form 1,2-bis(4-methoxyphenyl)ethyne (20a) was chosen to benchmark the catalysts, each in
monomeric form (Figure 12). In order to monitor their activity by NMR, the reaction was performed at
27°C in the absence of molecular sieves as 2-butyne-sequestering agent3 to avoid any interference.61
Therefore the reaction leads only to an equilibrium comprising ca. 45% of unreacted starting material.
1a as the prototype complex of the new series shows appreciable activity in that the equilibrium is
reached in  100 min.1 The reaction rate of 1b bearing fluorine substituents on the fence of the podand
ligand is identical, within experimental error, whereas 1c containing MeO-groups on the silanolate
propellers is slightly less active. The comparison of 1a and 1e, which differ from each other only in the
substitution pattern of the benzylidyne, shows that the 2,6-dimethyl substituted variant results in
markedly slower conversion even though equilibrium is eventually reached. This result must also be
seen in the light of the report by the Lee group, who found that their complex bearing a 2,4,6-
trimethylphenyl group induced scrambling of 1-methoxy-4-(phenylethynyl)benzene only upon
heating.2 Taken together, these observations indicate that 2,6-disubstitution of the benzylidyne group
causes slow(er) and/or incomplete initiation. Figure 12 also shows that complex 16 with the carbinol
ligand set exhibits much lower activity than 1a as the closest relative of the trisilanol series. This finding
is in line with the notion that silanols are privileged ligands for molybdenum alkylidynes.3,4
21
ACS Paragon Plus Environment

Journal of the American Chemical Society
Page 22 of 44
1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
Figure 12. Benchmarking Experiment (1H NMR): Consumption of 1-methoxy-4-(prop-1-yn-1-yl)benzene
(19) ([D8]-toluene, 0.1 M, 27°C, 5 mol% catalyst loading); the Insert shows that the reaction catalyzed
by 1f had reached equilibrium in less than 5 min, when the second data point was recorded
Although 1a is a competent catalyst, it does not rival the parent complex 2a carrying three simple
monodentate Ph3SiO-groups, which effects the model reaction in  10 min. In our preliminary
Communication we conjectured that the higher rigidity of the tripodal scaffold might be the reason
why the canopy variant 1a is about ten times slower than 2a.1 A stiffer backbone retards the changes
back and forth between tetrahedral and trigonal-bipyramidal coordination geometries of the reactive
intermediates passed through during a catalytic cycle. While this argument is certainly valid, the
improved understanding for the nature of 1 make us believe that additional factors might come into
play. The accumulation of metallatetrahedrane 18 (see Scheme 7) is arguably relevant in this context:
unless 18 itself is kinetically competitive, its formation in high concentration is a serious handicap as it
syphons much of the active species into an off-cycle reservoir.
In any case, it seems that the ligand design must somehow counteract the build-up of Lewis acidity
95
resulting from the distorted ligand sphere about the metal. Encouraged by the Mo NMR data, we
tested the activity of 1d and 1f bearing more donating alkyl substituents on the Si-bridges. The effect
is massive and the outcome extreme: 1d endowed with iso-propyl groups failed to catalyze the model
reaction at ambient temperature (but does so in refluxing toluene), whereas its sibling 1f bearing
22
ACS Paragon Plus Environment

Page 23 of 44
Journal of the American Chemical Society
1
2
3
4
5
6
7
8
9
methyl substituents is by far the most active precatalyst of the entire new series; it basically regains
the activity of the parent complex 2a (Figure 12). We tentatively ascribe the striking difference
between 1d and 1f to steric effects, supposing that the bulky iso-propyl moieties disfavor or even
prevent substrate binding (compare Figure 6). In any case, the performance of 1f is gratifying: this
“turbo catalyst” is as reactive as its best ancestors but outperforms them by far in terms of functional
group tolerance.
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
Scope and Applications. A truly comprehensive investigation into the functional group compatibility
of the canopy complexes is beyond the scope of this article, but the examples compiled below clearly
show their promise.
Table 2. Homo-Metathesis and Ring Closing Alkyne Metathesis Reactions in the Presence of
Unprotected –OH Groupsa
Entry
Substrate
Product
2a
1a
1f
1
20b
69%c
93%b
OH
OH
HO
2
3
4
5
21a, n = 4 0%
21b, n = 5 0%
21c, n = 6 0%
21d, n = 7 0%
69%
66%
83%
91%
73%
71%
88%
87%
OH
n
HO
n
HO
n
OH
OH
5
6
7
22
23
34%c
94%
5
OH
0%
dimersd 68%e
HO
OMOM
HO
OMOM
OMe
MeO
OMe
MeO
OH
NHBoc
TIPSO
NHBoc
8
9
TIPSO
24
25
16%f
0%
66%g
HO
O
OAc
O
MeOOC
HO
O
OAc
O
MeO
O
68%h
OH
O
N
RO
23
ACS Paragon Plus Environment

Journal of the American Chemical Society
Page 24 of 44
1
2
3
4
5
6
7
8
9
a isolated yields of reactions performed with 5 mol% of catalyst loading in toluene at RT in the presence
of MS 5Å, unless stated otherwise; b at 60°C; c with 10 mol% of 2a; d mostly formation of dimers (NMR);
e with 10 mol% of catalyst at 110°C; f yield determined by HPLC; in addition, ca. 20% of what appeared
to be dimeric products were detected; g with 20 mol% of catalyst at 80°C; h using 30 mol% of catalyst
at reflux temperature; yield over two steps (metathetic ring closure and reductive cleavage of the
2,2,6,6-tetramethylpiperidinyl group)
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
Scheme 8. The Positive Impact of the Chelate Effect
HO
7
(20 equiv.)
Me
Me
H2O (10 equiv.)
[D8]-toluene, RT
Ph3SiOH
Ph3SiOH
[D8]-toluene, RT
Mo
Ph3SiO
OSiPh3
5 min

, quant. Ph3SiO
5 min

, quant.
2b
HO
Me
Me
Ph
7
Ph
(20 equiv.)
H2O (10 equiv.)
[D8]-toluene
O
Ph
Ph
Mo Si
O
O
Si
toluene
quant.
Ph
Ph
Ph
91%
MS 5Å, RT
Si
9 h

, RT
1e
Ph
HO
HO
Ph
Ph
Si
HO
OH
7
Si
7
21d
OH
Ph
Ph
Si
11a
1f
(5 mol%), MS 5Å
OMe
OMe
MeO
technical grade toluene
(84 ppm H2O or 5300 ppm EtOH)
19
20a
(98%, NMR)
The direct comparison of the parent triphenylsilanolate complex 2a with the new catalysts 1a and 1f
is particularly instructive (Table 2): while 2a invariably failed to metathesize alkynes carrying
unhindered primary alcohol groups, both canopy complexes afforded the desired products in good to
excellent yields. As expected, catalyst 1f reacted much faster than 1a (ca. 2 h versus 16 h) but their
productivity is comparable, suggesting that different members of this family likely cover a similar
substrate scope. The superior performance of the new catalysts is further illustrated by the formation
of phenol 20b and product 22 carrying an ordinary secondary alcohol. The RCAM reaction leading to
24
ACS Paragon Plus Environment

Page 25 of 44
Journal of the American Chemical Society
1
2
3
4
5
6
7
8
9
23 containing two different propargylic substituents showcases two advantageous attributes at the
same time: 2a is unable to cope with the unprotected –OH group, whereas both new catalysts are;
however, only the slim “turbo catalyst” 1f provides the targeted cyclic monomer, whereas 1a gave
mostly dimeric products; this aspect becomes highly relevant in the context of the much more
demanding cycloalkyne 51 as the key precursor for the marine macrolide amphidinolide F (see below).
Compatibility with a propargylic –OH group is quintessential for the formation of 24: it is also of note
that two out of the three alkyne groups in the substrate reacted selectively.22 Once again, the
superiority of 1f is striking, since the standard catalyst 2a gave a poor yield and a bad mass balance.
Cycloalkyne 25 as the key intermediate of the first total synthesis of the marine nor-cembranoid
sinulariadiolide further illustrates the excellent application profile,62 in that the new catalyst tolerates
the free propargylic OH but also an electron rich enol ester as well as a hydroxylamine.
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
In line with our initial design concept, it is the chelate effect which largely accounts for the much
improved compatibility with unprotected OH groups; it even entails a certain meta-stability of the
canopy catalysts toward water (Scheme 8). Whereas addition of either a primary alcohol or H2O (10
equiv.) to a solution of 2b in [D8]-toluene results in almost instantaneous solvolysis (hydrolysis) with
quantitative release of Ph3SiOH ( 5 min, NMR), it takes 9 h until 1e is fully decomposed by water
under otherwise identical conditions. Importantly, the spectra do not provide any indication for
protonation of the alkylidyne: ligand exchange rather than destruction of the operative MoCR unit is
hence (mainly) accountable for loss of activity. This observation is in line with recent experimental as
well as computational data from the literature.21,63 Although water remains ultimately detrimental, a
half-life on the order of an hour is a chemical virtue without precedent in metal alkylidyne chemistry
in general; it is fully appreciated if one considers the extreme sensitivity of earlier generations of alkyne
metathesis catalysts, not least the otherwise very powerful complex 3 and its precursors.7-10,34,64 In this
context, we like to reiterate that it has become common practice to supplement the reaction mixtures
with molecular sieves:3,4 although this additive primarily serves as sequestering agent for the released
2-butyne in reactions conducted at RT, it ensures a level of dryness and hence a lifespan of a canopy
catalyst that allows certain applications to be carried out in technical grade solvents that need not be
rigorously dried and purified prior to use. Indeed, under these standard conditions, the test reaction
used to benchmark the catalyst performance proceeded quantitatively in technical grade toluene (87
25
ACS Paragon Plus Environment

Journal of the American Chemical Society
Page 26 of 44
1
2
3
4
5
6
7
8
9
ppm water) as well as in toluene containing residual EtOH (5300 ppm) in the presence of MS 5Å.
Although there is certainly very much room for improvement, these preliminary data are encouraging
and show that the podand ligand structure pays a valuable dividend in practical terms too.
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
Scheme 9. Homo-Metathesis Reactions of Substrates Comprising CH and/or NH acidic sitesa
O
O
O
O
OMe
O
4
OMe
MeO
O
O
O
MeO
4
O
[b]
O
27
91%
26
79%
H
O
OMe
NHBoc
SO2Ph
N
O
PhO2S
BocHN
O
N
O
OMe
H
28
67%
29
76%
a the reactions were performed with 1a (5 mol%) in toluene at RT in the presence of MS 5Å; b at 90°C
with 10 mol% of catalyst
Scheme 10. Survey of the Functional Group Tolerance: Homo-Metathesis Reactions
1a
1f
] or [ ] (5 mol%)
[
2
R
R
R
toluene, RT, MS 5Å
SMe
N
X
X
N
MeS
[b]
20a
92%, X = OMe
30
31
92%
62%[b] / 76%[b]
O
[a]
b
c
d
e
f
93%, X = OH
[a]
90%, X = CF3
S
[a]
77%, X = CN
OMe
MeO
98%, X = C(O)Me
NR, X = NO2
S
O
32
33
72%
91% / 85%
g
dec., X = CHO
NHBu
N
N
SC12H25
4
4
4
BuHN
4
H25C12
S
4
4
[a]
35
36
95%
88%
34
71%
O
OMe
I
N
OTs
N
4
MeO
I
TsO
4
O
37
38
39
82%
52%
83%
O
O
N
N
O
40
89%
O
the choice of catalyst is color-coded; a at 60°C; b at 90°C; NR = no reaction
26
ACS Paragon Plus Environment

Page 27 of 44
Journal of the American Chemical Society
1
2
3
4
5
6
7
8
9
In view of the foregoing, it will not come as a surprise that various other protic sites are also well
tolerated by the new catalysts, including a free phenol, amides, carbamates, malonates, -ketoesters,
sulfones, and the fluorenyl group (Table 2, Schemes 9-12). -Ketoesters in particular caused problems
in the past for the parent complexes 2,5 whereas the new catalyst 1a furnished product 26 containing
this common motif in good yield.
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
Since our spectral and computational data had suggested that the podand ligand architecture
upregulates the Lewis acidity, it was deemed equally important to prove that the new catalysts remain
active in the presence of various donor sites. Although gentle heating was necessary in several cases,
it is rewarding to find that basic nitrogen in form of a pyridine (31), a secondary or tertiary amine (34,
35), or a hydroxylamine (25) does not bring metathesis to a halt. The same is true for a nitrile-
containing compound (20d), even though the structure of adduct [1aMeCN] had shown that cyano
groups exhibit appreciable affinity to the molybdenum center.1 The good results with thioethers and
various sulfur-containing heterocycles (30, 32, 36, 47) are equally remarkable, as is the compatibility
with a Weinreb amide (37), which is a potential chelate ligand for a high-valent transition metal center.
Scheme 11. Ring Closing Alkyne Metathesis (RCAM): Test Reactionsa
O
O
O
O
O
O2N
O
O
O
O
6
6
n
O
O
O
[b]
[b]
41a
b
42
98%
95%, n = 1
85%, n = 3
43
98%
a Unless stated otherwise, all reactions were performed with 1a (5 mol%) in toluene in the presence of
powdered MS 5Å at ambient temperature; b at 60°C
Auspicious results were also obtained with yet other exigent functionality. An elimination-prone
primary tosylate and a primary iodide went uncompromised (38, 39). The ring closing alkyne
metathesis (RCAM) reaction leading to cycloalkyne 43 proves that a nitro group, as such, is compatible
(Scheme 11); however, attempted formation of the nitro-substituted tolane derivative 20f failed even
at elevated temperature. This limitation shows that electron-deficient alkynes in general are quite
refractory substrates.65 The observation that other products bearing electron-withdrawing
27
ACS Paragon Plus Environment

Journal of the American Chemical Society
Page 28 of 44
1
2
3
4
5
6
7
8
9
substituents required more forcing conditions corroborates this aspect (20c,d, 31). Attempted
formation of the aldehyde derivative 20g, however, resulted in decomposition. Aldehydes have
previously been found incompatible, a limitation that obviously persists;3-5 ketones, in contrast pose
no problem (20e, 26, 47).
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
Scheme 12. Formation of Key Intermediates of Previous Natural Product Total Synthesesa
a)
O
O
O
O
O
O
NFmoc
N
44
45
S
b)
OR
S
OR
N
O
N
O
O
H
OR O
O
H
OR O
46
, R = TBS
47
O
H
O
H
c)
OTBS
OTBS
O
OTBS
O
O
OTBS
O
48
49
OTES
OTES
OR
RO
d)
OR
RO
H
H
O
O
H
H
O
H
H
H
H
O
O
O
OR
O
OR
O
50
51
R = TBS
a Reagents and conditions: (a) 1a (5 mol%), toluene, MS 5Å, RT, quant.; (b) 1a (5 mol%), toluene, MS
5Å, 60°C, 75%; (c) 1a (5 mol%), toluene, MS 5Å, RT, 85%; (d) 1f (30 mol%), toluene, MS 5Å, 80°C, 81%
The rewarding outcome of the model reactions made us confident that the new catalysts qualify for
more advanced applications. Material from previous total synthesis campaigns from our laboratory
provided us with the opportunity to confirm this expectation. The two demanding cases 24 and 25
(Table 2) have already been discussed above in the context of the tolerance of the new catalysts
towards unprotected –OH groups. Next, we re-prepared product 45, which is a key precursor for the
synthesis of homoepilachnene, an ingredient of the defense secretions of the pupae of a Mexican
28
ACS Paragon Plus Environment

Page 29 of 44
Journal of the American Chemical Society
1
2
3
4
5
6
7
8
9
beetle (Scheme 12);66 although rather simple in structural terms, this example shows the compatibility
of 1a with a base-sensitive CH acidic fluorenyl group. Clearly more challenging is the formation of
cycloalkyne 47, which leads to the potent anticancer agent epothilone C upon Lindlar reduction of the
triple bond;67 the thiazole ring of 47 adds an important entry to the list of heterocycles that do not
quench the catalyst’s activity. Equally noteworthy is the fact that the elimination-prone aldol
substructure and the ketone are not affected. Even more compelling evidence for the mildness of the
method is found in the successful formation of 49, an immediate precursor of amphidinolide V:68 the
vinyl-epoxide and the allyl ether subunits are both sensitive to acid and/or base, yet remain intact. As
expected, the double bonds present in the substrate are tolerated, in line with observations already
made with previous generations of alkyne metathesis catalyst.3-10
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
The successful formation of 51 as the key intermediate en route to the marine toxin amphidinolide F69
illustrates yet another relevant aspect: only the slim “turbo-catalyst” 1f allowed this densely decorated
macrocycle to be formed in good yield, whereas 1a afforded acyclic dimers by homo-metathesis;
complex 2a with Ph3SiO- ligands had also largely caused homo-dimerization, most likely as a result of
steric hindrance about one of the double bonds in diyne 50.69 The leaner ligand sphere of 1f obviously
helps to overcome yet another of the few limitations that siloxide-based alkyne metathesis catalysts
had faced in the past (see also entry 7 in Table 2).19
Overall, the functional group tolerance of catalysts of type 1 is deemed remarkable and certainly
unrivaled by any other molecularly defined alkyne metathesis catalyst known to date. From the
conceptual viewpoint, this excellent profile may help to correct the common mis-perception that high-
valent early transition metal catalysts in general and MoVI-based alkylidyne and alkylidene catalysts in
particular provide only limited opportunities when working with polyfunctionalized compounds.70
Conclusions
The new family of well-defined molybdenum alkylidyne complexes endowed with a distinctive podand
topology outlined above is distinguished by good to excellent catalytic activity for alkyne metathesis
and a truly remarkable compatibility with exigent functionality, including various free –OH groups and
several other protic sites; it is largely due to the chelate effect that even a certain stability towards
water was noticed, which is without parallel in the literature. Since the preparation of the required
29
ACS Paragon Plus Environment