Grubbs Metathesis Enabled by a Light-Driven gem-Hydrogenation of Internal Alkynes

Article abstract of DOI:10.1002/anie.202007030

[(NHC)(cymene)RuCl₂] (NHC=N-heterocyclic carbene) complexes instigate a light-driven gem-hydrogenation of internal alkynes with concomitant formation of discrete Grubbs-type ruthenium carbene species. This unorthodox reactivity mode is harnessed in the form of a “hydrogenative metathesis” reaction, which converts an enyne substrate into a cyclic alkene. The intervention of ruthenium carbenes formed in the actual gem-hydrogenation step was proven by the isolation and crystallographic characterization of a rather unusual representative of this series carrying an unconfined alkyl group on a disubstituted carbene center.

Full text of DOI:10.1002/anie.202007030

A Journal of the Gesellschaft Deutscher Chemiker
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Accepted Article
Title: Grubbs Metathesis Empowered by a Light-Driven gem-
Hydrogenation of Internal Alkynes
Authors: Alois Fürstner, Tobias Biberger, and Raphael J. Zachmann
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Grubbs Metathesis Empowered by a Light-Driven gem-Hydrogenation of Internal Alkynes
Tobias Biberger, Raphael J. Zachmann, and Alois Fürstner*
Abstract: [(NHC)(cymene)RuCl2] (NHC = N-heterocyclic carbene) complexes instigate a light-driven
gem-hydrogenation of internal alkynes with concomitant formation of discrete Grubbs-type
ruthenium carbene species. This unorthodox reactivity mode is harnessed in form of a “hydrogenative
metathesis” reaction, which converts an enyne substrate into a cyclic alkene. The intervention of
ruthenium carbenes formed in the actual gem-hydrogenation step was proven by the isolation and
crystallographic characterization of a rather unusual representative of this series carrying an
unconfined alkyl group on a disubstituted carbene center.
It is textbook knowledge that the hydrogenation of an unsaturated substrate over a transition metal
catalyst proceeds in a suprafacial manner as long as it does not follow a radical path; cis-addition of
the H-atoms to the -system is the necessary outcome.1 This stereochemical paradigm was only
recently challenged when our group reported that [Cp*Ru]-based catalysts engage internal alkynes
into a trans-hydrogenation reaction with direct2 formation of E-alkenes.3,4,5,6 Combined experimental
and computational investigations showed that this perplexing outcome can actually be reached by two
different yet intertwined pathways (Scheme 1): once the substrate and H2 are uploaded onto the
ruthenium fragment as shown in A, a first hydrogen delivery leads to a ruthenacyclopropene B.4,5 It is
at this stage that the route bifurcates because either end of this intermediate can participate in the
subsequent hydrogen transfer step: reaction at C provides the E-alkene F via E in a concerted fashion,
whereas delivery at C generates a pianostool ruthenium carbene C in the first place (“gem-
hydrogenation”); this species then evolves into F by an associative mechanism, in which a second
molecule of H2 has to ligate the metal center to lower the barriers.4,5 For 2-butyne, the two pathways
*
T. Biberger, R. J. Zachmann, Prof. A. Fürstner
Max-Planck-Institut für Kohlenforschung
45470 Mülheim/Ruhr
Email: fuerstner@kofo.mpg.de
Supporting Information and ORCID identification number(s) of the authors of this article can be found under
###########
1
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have essentially identical barrier heights; substrates carrying propargylic heteroatom substituents able
to coordinate the ruthenium center, in contrast, are (strongly) biased for gem-hydrogention.4-6
Scheme 1. The interwoven pathways of trans- and gem-hydrogenation of alkynes; the dotted lines
indicate those steps downstream of gem-hydrogenation that need to be outperformed in order to
divert the pathway towards genuine carbene reactivity; Cp* = pentamethylcyclopentadienyl
Scheme 2. The prototype “hydrogenative metathesis” reaction involving pianostool ruthenium
carbene intermediates; [Ru] = Cp*RuCl
2
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Prior to this discovery, the formation of discrete metal carbene complexes by gem-hydrogenation was
unknown.6 If one is able to outperform the (facile) downstream evolution of C via D into the E-alkene
F, this unorthodox reactivity mode opens intriguing new vistas for hydrogenation at large. For the time
being, we managed to use gem-hydrogenation as an entirely new gateway to genuine carbene
chemistry in the form of hydrogenative ring expansion reactions,4 hydrogenative heterocycle
syntheses,4,7 and a counterintuitive hydrogenative cyclopropanation process.4,8,9 Moreover, it powers
the “hydrogenative metathesis” of enynes into cycloalkenes by intervention of pianostool ruthenium
carbenes of type G (Scheme 2); 8 the secondary carbene H released in the actual metathesis step is
then re-converted into [Cp*RuCl] as the propagating species by (hydrogenolytic) cleavage of the
organic ligand.8 As such, “hydrogenative metathesis” must be distinguished from traditional enyne
metathesis which leads to a 1,3-diene as the product;10 from the conceptual viewpoint, this
transformation hence represents a novel reactivity mode in the realm of metathesis.11
Proof-of-concept notwithstanding, a number of serious limitations remain to be addressed:8 (i) only
enynes with a steering –OR substituent at the propargylic position were found to be adequate
substrates; 1 (R = Me) is representative; (ii) even amongst this class of compounds, only tertiary
propargyl alcohol derivatives led to good yields, whereas their secondary cousins reacted much less
cleanly; (iii) the alkene site of the substrate must be trisubstituted; (iv) for the propensity of the
[Cp*Ru] fragment to engage in 6-binding with arenes, compounds containing (electron rich) aromatic
rings basically failed to react under the standard conditions; (iv) because the metathetic ring closure
needs to outperform the facile transformation of the carbene intermediate into the E-alkene (see
above), hydrogenative metathesis is essentially limited to the formation of five-membered rings; even
the kinetically only slightly less favorable closure of cyclohexene derivatives proved challenging and
required ligand tuning.8
On top of this list comes the fundamental question whether or not gem-hydrogenation by [CpXRu]
complexes is a singularity. Although we were able to demonstrate that the reaction is responsive to
changes of the electronic character of the CpX ring,8,12 it is perplexing that the truly massive literature
on catalytic hydrogenation gathered in over a century of intense research does not know of any other
catalyst that instigates this type of transformation. From the preparative viewpoint, the possibility to
change the ligand sphere and/or the central metal would arguably be of high significance. In a first
3
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foray into this uncharted territory, our search was focused on ancillary ligands other than CpX with the
hope of gaining a better understanding for gem-hydrogenation in general while overcoming some of
the limitations of “hydrogenative metathesis” outlined above.
Table 1. Hit finding and reaction optimization
Entry
R
L
Solvent
T (°C)
Conditions[a]
Yield (%)[b]
1
2
3
4
5
6
7
8
H
H
H
SIMes (4a)
IMes (4b)
IMes (4b)
IMes (4b)
IPr (4c)
IPr (4c)
IPr (4c)
4d
4e
4f
4g
PCy3
1,2-DCE
1,2-DCE
toluene
toluene
toluene
toluene
toluene
toluene
toluene
toluene
toluene
toluene
50[c]
50[c]
50[c]
50[c]
50[c]
60
UV-A
UV-A
UV-A
UV-A
UV-A
dark
8 (n. d.)
25 (n. d.)
66 (56)
85 (79)
quant. (95)
traces
traces
traces
traces
traces
traces
traces
[b]
Me
Me
Me
Me
Me
Me
Me
Me
Me
110
dark
50[c]
50[c]
50[c]
50[c]
50[c]
UV-A
UV-A
UV-A
UV-A
UV-A
9
10
11
12
[a]
UV-A refers to irradiation with a lamp with an emission maximum at 370 nm; for details, see the SI; NMR
yield (isolated yield of analytically pure product); [c] 50°C is the temperature reached upon irradiation of the
mixture; no external heating bath was used; 1,2-DCE = 1,2-dichloroethane; n. d. = not determined
Our quest was guided by the perception that any alternative catalyst should provide  in analogy to
the successful [Cp*Ru] fragment  (up to) three binding sites preferentially in a facial array for proper
upload of substrate and H2 (as -complex or, after oxidative insertion, in form of two hydride
ligands).4,5,13 Careful balancing of the electron density at the central metal was deemed yet another
4
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critically important aspect: the catalyst must be notably carbophilic and -acidic to ensure the
necessary activation of the triple bond;14 at the same time, however, the ligand sphere should push
electron density into the hydrides to facilitate attack onto the co-ligated -system. It was hoped that
such a local electronic asymmetry about the central atom might be crafted by an appropriate
combination of ligands with different trans-influence.
With these notions in mind, a small set of precatalysts was screened and a first hit obtained with
complex 3a (L = SIMes);15 however, it required authentic 28 to prove that the crude mixture formed
upon hydrogenation of 1a (R = H) with 3a (10 mol%) under concomitant UV irradiation contained 8%
(NMR) of the desired metathesis product. These conditions were chosen because (photochemical) de-
coordination of p-cymene from a complex of type 3 vacates three binding sites and the released 12-
electron fragment [(SIMes)RuCl2] comprises two ligands of largely different donor character.16
Subsequent optimization revealed the following facts and trends: (i) NHC’s with an unsaturated
backbone gave better results than their saturated cousins;17,18 (ii) the nature of the N-substituent is
also important even though its exact role remains to be elucidated:19 for the time being, [(IPr)(6-
cymene)RuCl2] (3c) works best, followed by [(IMes)(6-cymene)RuCl2] (3b); the use of related NHC’s
(4d-g) as ancillary ligands resulted in failure;20 (iii) likewise, replacement of the NHC by R3P (R = Cy, Ph)
brings hydrogenative metathesis to a hold; (iv) constant irradiation of the reaction mixture with a UV
lamp is necessary;21 attempts to drive the reaction by thermal de-coordination of the p-cymene ligand
led to mixtures that contain only minute amounts of the desired product;22 (v) while the [Cp*Ru]
catalysts previously used operate best in chlorinated media,8 the switch from 1,2-dichloroethane to
toluene resulted in a significant increase in yield; (vi) just like in our previous study on gem-
hydrogenation,8 the substitution of the alkene strongly impacts on the outcome; enyne 1b (R = Me)
bearing a methyl cap on the olefinic site proved to be optimal. When the reaction of this substrate is
carried out with 3c (10 mol%) in toluene under H2 atmosphere (balloon) and irradiation with a UV lamp
( = 370  40 nm), the metathesis reaction is remarkably clean and essentially quantitative (see the
SI), affording analytically pure 2 in 95% yield after flash chromatography.
5
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Scheme 3. Light-driven hydrogenative metathesis of enyne substrates: assortment of cycloalkene
[a]
products and proposed catalytic cycle; all reactions were carried out under H2 atmosphere with
[(IPr)(6-cymene)RuCl2] (3c, 10 mol%) in toluene under constant UV irradiation; unless stated
otherwise, the yields refer to analytically pure products; [b] using 20 mol% of the catalyst; [c] NMR yield;
S = solvent; MOM = methoxymethyl; THP = tetrahydropyranyl; Ts = p-toluenesulfonyl (tosyl)
The products compiled in Scheme 3 were formed under these standard conditions.23 As expected,
enynes carrying a propargylic –OR substituent gave good to excellent results, even if the steering group
was a secondary rather than tertiary proparyl alcohol derivative. Importantly, several enynes devoid
of any such propargylic substituent reacted equally well; such substrates had been beyond the scope
6
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of the original [Cp*Ru]-based system.8 In case of 11, hyperconjugation between the silicon substituent
and the emerging electrophilic carbene is thought to dictate the regiochemical course of the gem-
hydrogenation and hence the site of metathetic ring closure, even though steric effects definitely play
a role too.24 This notion is supported by the fact that the adamantyl derivative 12 was equally formed
as a single regioisomer in essentially quantitative yield: note that the transient carbene must have
resided distal to the bulky caged substituent. Likewise, an electron rich and bulky ferrocene moiety
entails regioselective ring closure to give 13, again via transient carbene formation at the alkyne’s distal
site. In contrast, the triple bond of (substituted) phenyl acetylenes is not sufficiently biased on
electronic and/or steric grounds: as a result, gem-hydrogenation occurs at either end, thus leading to
product mixtures, independent of whether the phenyl group carries an electron-donating or
withdrawing substituent (14a-d). Importantly, however, these and several other examples shown in
Scheme 3 demonstrate that the new catalyst system works well in the presence of aromatic groups,
even if they are electron rich. The fact that six-membered rings can also be closed with appreciable
yields marks yet another notable step forward. This progress notwithstanding, attempted formation
of larger carbo- and heterocycles has so far basically met with failure.
Although these data suggest that Grubbs-type carbenes of type I are generated in situ by alkyne gem-
hydrogenation as the actual reactive intermediates,11,25,26 additional experimental support was sought
to corroborate this claim. Since the use of para-H2, which had proven very useful for the study of the
reactivity of [Cp*Ru]-based catalysts, is to no avail in the present case,4,5,27 other control experiments
were carried out to confirm or disprove the intervention of discrete ruthenium carbene intermediates
in the new reaction set-up. To this end, alkyne 19 was hydrogenated under UV-irradiation with a
stoichiometric amount of 3b (Scheme 4): NMR inspection of the crude mixture showed a diagnostic
signal at C = 314.5 ppm; the expected carbene complex 20 could indeed be isolated in analytically
pure form. The modest yield of 31% is mainly due to competing dimerization of 19 with formation of
diene 21, most likely by oxidative cyclization and subsequent hydrogenolytic cleavage of the resulting
metallacycle.28 The formation of 20 does prove that a net gem-hydrogenation of the triple bond of the
alkyne must have taken place that leads to the formation of a genuine five-coordinate “second
generation” Grubbs-type carbene complex.29 Actually, 20 seems to be the first example of a fully
characterized Grubbs-type catalyst carrying two substituents on the carbene unit, one of which is an
7
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unconfined alkyl group.30,31,32 Although the transient formation of such species can be inferred from
the literature,11 20 shows that such complexes do not degrade by the common decomposition
pathways such as 1,2-hydride or 1,2-alkyl shift which plague non-stabilized electrophilic metal
carbenes otherwise.33 Complex 20 is stable under the photochemical conditions under which it is
formed and decomposition by bimolecular coupling of the carbene was not observed to any noticeable
extent; once isolated, it can be stored on the bench for extended periods of time and can be used in
lieu of the commercial “second generation” Grubbs or Grubbs-Hoveyda catalysts34 as proven by the
RCM reaction leading to product 23.
Scheme 4. Light-driven gem-hydrogenation with formation of a Grubbs-Hoveyda-type catalyst
Figure 1. Structure of complex 20 in the solid state; arbitrary numbering scheme.35
8
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The structure of 20 in the solid state deserves particular attention (Figure 1).35 Since coordination of
the tethered ether-O-atom onto the Ru center locks the carbene in place, the ethyl substituent is
forced to reside directly under the umbrella of one of the two mesityl groups. Even though this N-
substituent turns about the N1-C25 bond in order to provide more space (C1-N1-C25-C30 97.9(1)°, C1-
N1-C25-C26 89.0(1)°) and the entire NHC ligand tilts away from linearity (N1-C1-Ru1 136.0(1)°, N2-C1-
Ru1 119.6(1)°),36 the clash between the ethyl group and the ancillary ligand is massive: the distances
between H11a and C25, C26, C31 and H31a are (well) below the sum of the van-der-Waals radii of
these atoms. The strong puckering of the oxa-ruthenacycle is yet another consequence of the crowded
situation (see the SI). The strain manifested in these structural attributes is thought to be a major
reason why the formation of this particular complex by gem-hydrogenation is rather low-yielding;
future ligand design must take these issues into consideration.
Scheme 5. Headspace analysis showing the fate of the secondary carbene formed in the actual
metathesis step: a) 3b (10 mol%), H2 (1 atm), UV-A, toluene
As mentioned above, “hydrogenative metathesis” of an enyne involves two different metal carbenes
(Scheme 3): the first such species formed by gem-hydrogenation of the alkyne unit reacts with the
alkene to give the metathesis product with concomitant release of a secondary carbene. For the
catalytic cycle to be closed, this secondary carbene must be reconverted into the propagating
ruthenium species at a rate that prevents side reactions from occurring: if it accumulates, the process
transmutes into an ordinary enyne metathesis furnishing a 1,3-diene as the product. In case of the
[Cp*Ru]-based system originally disclosed by our group (Scheme 2), hydrogenolytic cleavage of the
organic ligand is responsible for the regeneration of the active catalyst.8 For the new light-driven
method, however, all evidence suggests that bimolecular coupling rather than hydrogenolytic
9
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cleavage37 of the carbene moiety is the major pathway (Scheme 5). Specifically, the secondary carbene
J derived from 1a is a ruthenium methylidene, but head-space analysis showed that 82% of the
released gas consists of ethene and ethane; in analogy, the internal alkene 1b leads to a ruthenium
ethylidene, but C4 compounds dominate amongst the decomposition products.38 The fact that the
amount of C3 products in the headspace increased significantly (at the expense of the C2 and C4
products) when a 1:1 mixture of 1a and 1b was reacted under standard conditions is particularly
indicative. Regeneration of the active catalyst by this bimolecular process may also explain why the
degree of substitution of the olefin in the substrate is linked to the overall efficiency of the
hydrogenative metathesis reaction: with one methyl group, the secondary carbene J is sufficiently
stabilized to render the dimerization clean in order not to lose too much catalyst per turn-over,39 but
it is neither over-stabilized nor overcrowded to impede the reaction. In any case, the results of the
headspace analysis are in excellent accord with studies into the decomposition pathways of Grubbs
catalysts which unveiled the ease of bimolecular methylidene coupling of intermediates of type
[(SIMes)(Cl2)Ru=CH2].39,40,41 Computational data corroborate the experimental results in that the
corresponding transition state was found to be remarkably low-lying.42 At the meta-level, it is therefore
interesting to note that the role of bimolecular coupling is fundamentally different in the present
context: rather than being the chief destructive element,39-42 this process has become the key enabling
feature of the catalytic cycle, without which the new light-driven hydrogenative metathesis reaction
would not be able to proceed.
In line with the notion that bimolecular coupling is quintessential for maintaining catalytic turnover,
the Grubbs-Hoveyda-type complex 20 itself  though formed by a light-driven gem-hydrogenation
event  is not a competent catalyst for hydrogenative enyne metathesis because the disubstitued
carbene moiety is simply too reluctant.43 In contrast, the slim Grubbs ethylidene complex 24 (20 mol%)
– though ligated to two additional pyridine ligands  is able to convert enyne 1b into product 2 in 64%
yield under the standard reaction conditions (H2, toluene, UV-A light, ca. 50°C) (Scheme 6). As this
control experiment is based on an orthogonal entry point into the catalytic cycle, it provides
independent support for the proposed mechanism.
10
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Scheme 6. A Grubbs-type ruthenium ethylidene complex as an alternative entry point; R = 2,6-
diisopropylphenyl
The reasons why the reaction mixture must be permanently irradiated with UV light in order to achieve
full and clean conversion are by no means clear at this point. In accord with literature data,16 our
control experiments confirmed that cymene decomplexation from the precatalyst 3 proceeds without
problem at elevated temperatures in the dark (see the SI); hence, the role of the light is more
intricate.44,45 Recent studies, which draw an integral picture of metathesis including the fate of the
catalyst might provide hints:42 specifically, DFT analysis showed that thermal decomplexation of the p-
cymene ligand from [(SIMes)(p-cymene)RuCl2] delivers the 12-electron fragment [(SIMes)RuCl2] as
spin-singlet; this species is extremely electron-deficient and readily inserts into the C-H bonds of an N-
mesityl group of the SIMes ligand. In contrast, decomposition of a Hoveyda-type catalyst generates
the analogous spin-triplet 3[(SIMes)RuCl2] which shows a notably different chemical behavior in that it
preferentially engages with alkenes.42 It is tempting to speculate that light is needed in the new
hydrogenative metathesis reaction to connect the two spin surfaces.46 In any case, it will be interesting
to study the reactivity of the two spin-isomers vis-à-vis H2 and alkynes. The question whether or not
the current reaction is another incarnation of two-state reactivity47 and other open mechanistic
aspects deserve detailed scrutiny by a combined experimental and computational approach.
In summary, we document herein the only second example of a catalyst that is capable of effecting the
net geminal delivery of the two H-atoms of H2 to one and the same C-atom of an alkyne substrate. In
contrast to the only literature precedent,4-8 the new gem-hydrogenation manifold is light-driven and
11
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leads to the formation of second-generation Grubbs-type complexes as the key reactive intermediates.
Although numerous aspects remain to be addressed and the maturity and scope of the transformation
to be improved, it is clear that catalytic hydrogenation opens a non-canonical and orthogonal entry
into the cosmos of Grubbs catalysis.11 Further studies intending to harness the power of this and
related gem-hydrogenation reactions are underway in this laboratory.
Acknowledgements
Generous financial support by the MPG is gratefully acknowledged. We thank all analytical
departments of our Institute for excellent support, especially J. Rust and Prof. C. W. Lehmann for
solving the X-ray structure of complex 20, V. Dietl for numerous GC analyses, and Dr. M. Klußmann,
Dr. M. Leutzsch and Dr. P. Schulze for valuable discussions.
For the Table of Contents
Enlightenment: The hydrogenation of enynes with [(NHC)(cymene)RuCl2] (NHC = N-heterocyclic
carbene) complexes under UV irradiation leads to the formation of cyclic alkenes by intervention of
Grubbs-type ruthenium complexes. This unorthodox entry into the realm of metathesis chemistry
represents the first light-driven catalyst system able to instigate alkyne gem-hydrogenation with
concomitant formation of a discrete metal carbene species.
Keywords: Grubbs catalysts  gem-Hydrogenation  Metal Carbenes  Metathesis  Ruthenium
12
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1
a) P. N. Rylander, Hydrogenation Methods; Academic Press: London, 1985; b) M. Hudlicky,
Reductions in Organic Chemistry, 2nd Ed., ACS, Washington 1996; c) Handbook of Homogeneous
Hydrogenation (J. G. de Vries, C. J. Elsevier, Eds.), Wiley-VCH: Weinheim, 2007.
Many cases are known in which E-alkenes are formed from alkynes as by-products or even as
the major product of a hydrogenation reaction; it is important to note that they usually originate
from secondary ZE-alkene isomerization and not from direct trans-hydrogenation; for a
discussion and a compilation of pertinent references, see ref. 4,6
2
3
4
5
a) K. Radkowski, B. Sundararaju, A. Fürstner, Angew. Chem. Int. Ed. 2013, 52, 355-360; b) M.
Fuchs, A. Fürstner A. Angew. Chem., Int Ed. 2015, 54, 3978-3982.
A. Guthertz, M. Leutzsch, L. M. Wolf, P. Gupta, S. M. Rummelt, R. Goddard, C. Farès, W. Thiel, A.
Fürstner, J. Am. Chem. Soc. 2018, 140, 3156-3168.
M. Leutzsch, L. M. Wolf, P. Gupta, M. Fuchs, W. Thiel, C. Farès, A. Fürstner, Angew. Chem. Int.
Ed. 2015, 54, 12431-12436.
6
7
8
9
A. Fürstner, J. Am. Chem. Soc. 2019, 141, 11-24.
S. Peil, A. Fürstner, Angew. Chem. Int. Ed. 2019, 58, 18476-18481.
S. Peil, A. Guthertz, T. Biberger, A. Fürstner, Angew. Chem. Int. Ed. 2019, 58, 8851-8856.
Cyclopropanes are normally cleaved rather than formed by catalytic hydrogenation; therefore a
“hydrogenative cyclopropanation” reaction is deemed counterintuitive.
10
a) E. C. Hansen, D. Lee, Acc. Chem. Res. 2006, 39, 509-519; b) S. T. Diver, A. J. Giessert, Chem.
Rev. 2004, 104, 1317-1382; c) C. S. Poulsen, R. Madsen, Synthesis 2003, 1-18; d) A. Fürstner,
Angew. Chem. Int. Ed. 2000, 39, 3012-3043.
11
12
R. H. Grubbs, D. J. O’Leary (Eds.), Handbook of Metathesis, 2nd Ed., Wiley-VCH, Weinheim, 2015.
T. Biberger, C. P. Gordon, M. Leutzsch, S. Peil, A. Guthertz, C. Copéret, A. Fürstner, Angew. Chem.
Int. Ed. 2019, 58, 8845-8850.
13
For alkyne coordination onto [Cp*Ru] fragments, see: a) D.-A. Rosca, K. Radkowski, L. M. Wolf,
M. Wagh, R. Goddard, W. Thiel, A. Fürstner, J. Am. Chem. Soc. 2017, 139, 2443-2455; b) S. M.
Rummelt, K. Radkowski, D.-A. Rosca, A. Fürstner, J. Am. Chem. Soc. 2015, 137, 5506-5519; c) X.
Mo, A. Letort, D.-A. Rosca, K. Higashida, A. Fürstner, Chem. Eur. J. 2018, 24, 9667-9674.
14
A. Fürstner, P. W. Davies, Angew. Chem. Int. Ed. 2007, 46, 3410-3449.
13
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15
C. S. Day, D. E. Fogg, Organometallics 2018, 37, 4551-4555.
16
Complexes of type [(6-arene)(L)RuX2] (L = two-electron donor ligand, X= anionic ligand) have a
good track record as precatalysts for olefin metathesis, using different procedures for their
initiation; for leading references, see the following and literature cited therein: a) A. W. Stumpf,
E. Saive, A. Demonceau, A. F. Noels, J. Chem. Soc. Chem. Commun. 1995, 1127-1128; b) A.
Hafner, A. Mühlebach, P. A. van der Schaaf, Angew. Chem. Int. Ed. 1997, 36, 2121-2124; c) A.
Fürstner, M. Picquet, C. Bruneau, P. H. Dixneuf, Chem. Commun. 1998, 1315-1316; d) A.
Fürstner, L. Ackermann, Chem. Commun. 1999, 95-96; e) L. Jafarpour, J. Huang, E. D. Stevens, S.
P. Nolan, Organometallics 1999, 18, 3760-3763; f) A. Fürstner, M. Liebl, C. W. Lehmann, M.
Piquet, R. Kunz, C. Bruneau, D. Touchard, P. H. Dixneuf, Chem. Eur. J. 2000, 6, 1847-1857; g) C.
Lo, R. Cariou, C. Fischmeister, P. H. Dixneuf, Adv. Synth. Catal. 2007, 349, 546-550; h) M. R.
Buchmeiser, D. Wang, Y. Zhang, S. Naumov, K. Wurst, Eur. J. Inorg. Chem. 2007, 3988-4000; i) D.
S. Miller, Y. Raoul, J. Le Nôtre, O. Baslé, M. Mauduit, ACS Catal. 2019, 9, 3511-3518.
In conventional metathesis, second generation catalysts with saturated NHC’s tend to be
(slightly) more active; for reviews see: a) G. C. Vougioukalakis, R. H. Grubbs, Chem. Rev. 2010,
110, 1746-1787; b) C. Samojiowicz, M. Bieniek, K. Grela, Chem. Rev. 2009, 109, 3708-3742.
For early contributions of this group on “second generation” catalysts carrying unsaturated
NHC’s, see: a) L. Ackermann, A. Fürstner, T. Weskamp, F. J. Kohl, W. A. Herrmann, Tetrahedron
Lett. 1999, 40, 4787-4790; b) A. Fürstner, O. R. Thiel, L. Ackermann, H.-J. Schanz, S. P. Nolan, J.
Org. Chem. 2000, 65, 2204-2207. c) L. Ackermann, D. El Tom, A. Fürstner, Tetrahedron 2000, 56,
2195-2202. d) A. Fürstner, L. Ackermann, B. Gabor, R. Goddard, C. W. Lehmann, R. Mynott, F.
Stelzer, O. R. Thiel, Chem. Eur. J. 2001, 7, 3236-3253.
17
18
19
For a recent review on the use of ruthenium NHC complexes in hydrogenation reactions, see: D.
A. Hey, R. M. Reich, W. Baratta, F. E. Kühn, Coord. Chem. Rev. 2018, 174, 114-132.
20
21
Imidazolium salts was not detected by NMR in the crude reaction mixtures.
Most experiments were performed in a quartz Schlenk tube, but control experiments showed
that ordinary laboratory glassware (Pyrex) can also be used; for details, see the SI.
22
The same is true for experiments in which decoordination was photochemically triggered but
the light was then switched off and the mixture then heated in the dark.
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The E-alkene formed by trans-hydrogenation of the substrate as well as over-reduction products
are commonly found as trace impurities in the crude reaction mixtures.
24
For a recent study into the gem-hydrogenation of silylated alkynes, see: L. Song, Q. Feng, Y.
Wang, S. Ding, Y.-D. Wu, X. Zhang, L. W. Chung, J. Sun, J. Am. Chem. Soc. 2019, 141, 17441-17451.
R. H. Grubbs, Angew. Chem. Int. Ed. 2006, 45, 3760-3765.
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26
The formation of Grubbs-type carbenes from terminal alkynes and H2 is known; mechanistically,
this transformation is fundamentally different from the gem-hydrogenation described herein in
that a ruthenium vinylidene is initially formed, which is then protonated to give the final
carbene; because of the need to form a vinylidene complex, this process is limited to terminal
alkynes (including acetylene), cf: a) J. Wolf, W. Stüer, C. Grünwald, H. Werner, P. Schwab, M.
Schulz, Angew. Chem. Int. Ed. 1998, 37, 1124-1126; b) J. Wolf, W. Stüer, C. Grünwald, O. Gevert,
M. Laubender, H. Werner, Eur. J. Inorg. Chem. 1998, 1827-1834.
27
The pianostool carbenes derived from [Cp*RuX]-based catalysts are chiral-at-metal and the
adjacent methylene group formed by gem-hydrogenation hence prochiral; this precondition for
signal enhancement by para-hydrogen induced polarization transfer (PHIP) is not met by Grubbs
carbene complexes.
28
Traces of other by-products were also detected in the crude mixture; for a discussion of how
metallacycle formation can interfere with the hydrogenation of propargylic substrates, see: a)
S. M. Rummelt, G.-J. Cheng, P. Gupta, W. Thiel, A. Fürstner, Angew. Chem. Int. Ed. 2017, 56,
3599-3604; corrigendum: Angew. Chem. Int. Ed. 2017, 56, 5652; for a computational study, see:
b) M. Gierada, I. Czelusniak, J. Handzlik, Mol. Catal. 2019, 469, 18-29.
29
30
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The light-driven gem-hydrogenation is almost certainly a non-concerted process, as indicated by
the fact that the hydrogenations of 1b carried out under an atmosphere of H2/D2 (1:1) led to a
mixture of 2 (42%), [D]-2 (34%) and [D2]-2 (24%) (NMR).
For constrained relatives of the cyclopropylidene or cyclobutylidene series, see: a) Z. Wu, S. T.
Nguyen, R. H. Grubbs, J. W. Ziller, J. Am. Chem. Soc. 1995, 117, 5503-5511; b) F. Lopez, A.
Delgado, J. R. Rodriguez, L. Castedo, J. L. Mascarenas, J. Am. Chem. Soc. 2004, 126, 10262-10263.
A related complex, in which the Ru center carries a hydride and a chloride ligand, see: A. Collado,
M. A. Esteruelas, E. Onate, Organometallics 2011, 30, 1930-1941.
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The most common metathesis catalyst with a disubstitued carbene center are complexes of the
indenylidene series, in which both substituents are sp2-hydridized, see: a) A. Fürstner, O. Guth,
A. Düffels, G. Seidel, M. Liebl, B. Gabor, R. Mynott, Chem. Eur. J. 2001, 7, 4811-4820; b) A.
Fürstner, O. R. Thiel, J. Org. Chem. 2000, 65, 1738-1742.
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R. H. Crabtree, The Organometallic Chemistry of the Transition Metals, 4th Ed., Wiley, Hoboken,
2005.
a) S. B. Garber, J. S. Kingsbury, B. L. Gray, A. H. Hoveyda, J. Am. Chem. Soc. 2000, 122, 8168-8179;
b) S. Gessler, S. Randl, S. Blechert, Tetrahedron Lett. 2000, 41, 9973-9976; c) A. H. Hoveyda, D.
G. Gillingham, J. J. Van Veldhuizen, O. Kataoka, S. B. Garber, J.S. Kingsbury, J. P. A. Harrity, Org.
Biomol. Chem. 2004, 2, 8-23.
35
CCDC 2004044 contains the supplementary crystallographic data. These data can be obtained
free of charge from the Cambridge Crystallographic Data Centre.
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37
Despite the strain, a 5 value of 0.18 indicates that the overall coordination geometry of 20 is
still close to square pyramidal.
For studies on hydrogenolysis of Grubbs-type complexes, see: a) S. D. Drouin, G. P. A. Yap, D. E.
Fogg, Inorg. Chem. 2000, 39, 5412-5414; see also: b) M. Olivan, K. C. Caulton, Inorg. Chem. 1999,
38, 566-570.
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The C2/C3/C4 ratio does not change to any significant extent upon changing the catalyst
concentration (5-20 mol%); higher loadings, however, lead to an increased alkane content by
hydrogenation of the alkenes primarily formed; for details, see the Supporting Information.
For the “first generation” Grubbs catalysts, it is known that substituted carbenes decompose
mainly through bimolecular pathways, whereas the methylidene complex degrades
unimolecularly, see: M. Ulman, R. H. Grubbs, J. Org. Chem. 1999, 64, 7202-7207. In the present
case, any competing unimolecular process would likely deplete the system in active ruthenium.
G. A. Bailey, M. Foscato, C. S. Higman, C. S. Day, V. R. Jensen, D. E. Fogg, J. Am. Chem. Soc. 2018,
140, 6931-6944.
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41
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Y. Schrodi, in Handbook of Metathesis, 2nd Ed., Wiley-VCH, Weinheim, 2015, Vol. 1, pp. 323-342.
a) J. Engel, W. Smit, M. Foscato, G. Occhipinti, K. W. Törnroos, V. R. Jensen, J. Am. Chem. Soc.
2017, 139, 16609-16619; b) W. Smit, M. Foscato, G. Occhipinti, V. R. Jensen, ACS Catal. 2020, 10,
6788-6797.
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The “second generation” Grubbs catalyst is no adequate precatalyst for hydrogenative
metathesis of enynes either; the failure is tentatively ascribed to the presence of a PCy3 ligand,
which the control experiments compiled in Table 1 had shown to quench any activity.
Several reports on the use of [(6-arene)(L)RuX2] as precatalysts for regular olefin metathesis
also mandate photochemical (not thermal) activation, cf. ref. 16b,d,f
44
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For a general review on the photochemistry of transition metal hydride complexes, see: R. N.
Perutz, B. Procacci, Chem. Rev. 2016, 116, 8506-8544.
Another potentially relevant aspect was reported by Fogg and coworkers, who showed that the
decompositon of [(SIMes)(6-cymene)RuCl2] follows a first-order rate law under photochemical
but a second-order rate law under thermal conditions, see ref. 15
47
D. Schröder, S. Shaik, H. Schwarz, Acc. Chem. Res. 2000, 33, 139-145.
17
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