Rendering schrock-type molybdenum alkylidene complexes air stable: User-friendly precatalysts for alkene metathesis

Article abstract of DOI:10.1002/anie.201102012

A matter of convenience: Schrock molybdenum alkylidenes are amongst the most powerful olefin metathesis catalysts known to date, but their sensitivity to air and moisture mandates their handling in a glove-box or by Schlenk techniques. This inconvenience is circumvented by using the corresponding phenanthroline- or bipyridine adducts, which are bench-stable and hence very user-friendly. The active species can be liberated from these precatalysts in uncompromised form on treatment with ZnCl₂ in toluene (see scheme).

Full text of DOI:10.1002/anie.201102012

DOI: 10.1002/anie.201102012
User-Friendly Catalysts
Rendering Schrock-type Molybdenum Alkylidene Complexes Air
Stable: User-Friendly Precatalysts for Alkene Metathesis**
Johannes Heppekausen and Alois Fꢀrstner*
Complex 1 and related tetracoordinate molybdenum alkyli-
denes developed by Schrock and co-workers range amongst
the most powerful alkene metathesis catalysts known to
date.[1,2] They are distinguished by exceptional reactivity,
good functional group tolerance and a remarkable scope,
encompassing olefins that are considered difficult substrates
on steric and/or electronic grounds.[3,4] The modularity of the
established synthesis route allowed the operative motif of 1 to
be systematically edited and hence gave rise to several
generations of descendant catalysts with tailored properties.
Most notable among them are Schrock alkylidenes with chiral
alkoxide or diolate ligands and/or alkylidenes that are chiral
at metal for all sorts of asymmetric metathesis reactions,[3,5] as
well as catalysts that impose high Z-selectivity on certain
metathesis reactions.[6]
complex 4[11] and the chiral variant 6[12] also form adducts
that remain intact when stored without any precautions for
extended periods (Scheme 1).
As complex 1 and relatives, however, are very sensitive to
air and moisture, their handling is clearly more demanding
than that of the competing ruthenium carbenes introduced by
Grubbs.[7] To overcome this disadvantage, we now present a
simple way of rendering prototype Schrock alkylidenes
largely air-stable, which facilitates their handling and may
hence encourage more widespread use of these able catalysts
in preparative laboratories.
Based on recent observations made in the alkyne meta-
thesis arena,[8,9] solutions of 1 in toluene were reacted at room
temperature with equimolar amounts of 1,10-phenanthroline
or 2,2’-bipyridine. The resulting crystalline adducts 2 and 3
turned out to be surprisingly robust in the solid state as well as
in solution.[10] Their integrity can be easily checked by NMR
spectroscopy due to the characteristic downfield shift of the
alkylidene proton from dH(CD2Cl2) = 12.19 ppm in the parent
complex 1 to dH(CD2Cl2) = 13.88 and 13.74 ppm in 2 and 3,
respectively. According to this distinctive signature, a sample
of the bipyridine adduct 3 stored at the bench in an open flask
was fully intact after eight weeks, whereas the corresponding
phenanthroline adduct 2 was found to be somewhat less stable
(only ca. 50% intact after four weeks). Other prototype
molybdenum alkylidenes such as the triphenylsilanolate
Scheme 1. a) 1,10-Phenanthroline, toluene, RT, 95% (2), 81% (5a),
85% (5b); b) 2,2’-bipyridine, toluene, RT, 93% (3); c) 2,2’-bipyridine,
Et2O, RT, 74% (7); Ar=2,6-diisopropylphenyl.
The structure of the particularly robust complex 3 in the
solid state is depicted in Figure 1. The coordination geometry
about the MoVI center can be described as distorted octahe-
dral, with the imido ligand and one of the two inequivalent
hexafluoro-tert-butanolates residing trans to each other, even
though the corresponding N3-Mo1-O2 angle (167.04(4)8)
strongly deviates from linearity. Likewise, the angle between
the alkylidene C19 carbon and the trans-positioned N2 atom
of the bipyridine is reduced to 167.02(4)8. The distortion of
the ligand sphere also manifests in very uneven bond
distances between the Mo center and the N atoms of the
[*] Dipl.-Chem. J. Heppekausen, Prof. A. Fꢀrstner
Max-Planck-Institut fꢀr Kohlenforschung
45470 Mꢀlheim/Ruhr (Germany)
E-mail: fuerstner@kofo.mpg.de
[**] Generous financial support by the MPG and the Fonds der
Chemischen Industrie is gratefully acknowledged. We thank Dr.
C. W. Lehmann and J. Rust for solving the X-ray structures and all
analytical departments of our institute for their excellent support of
our program.
À
chelating bipyridine unit. The fact that the Mo1 N2 bond
(2.3503(11) ꢀ) is considerably longer than the corresponding
À
Mo1 N1 bond (2.2462(10) ꢀ) reflects the significant trans
influence of the alkylidene unit[13] and may be an essential
structural precondition for the decomplexation behavior
Supporting information for this article is available on the WWW
under http://dx.doi.org/10.1002/anie.201102012.
À
described below. The alkylidene Mo1 C19 bond length
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pyridine, quinuclidine), in which the coordination of the base
is partially reversible in solution at ambient temperature,[15]
the NMR spectra of 2, 3, 5, and 7 give no indications for
partial dissociation of the chelating bipyridine or phenanthro-
line residues.[16] As a result, these complexes are devoid of
catalytic activity in prototype ring closing metathesis (RCM)
reactions even at higher temperatures. Gratifyingly though,
the bidentate N ligands can be readily pulled off upon
treatment of these adducts with one equivalent of anhydrous
ZnCl2 in toluene at ꢀ 1008C, thus releasing the structurally
intact and catalytically competent parent Schrock alkylidene
from which they derive. As judged by NMR spectroscopy, the
reaction is complete in less than 30 min.[17] It is believed that
the structural distortion of the adducts and, in particular, the
À
weakened Mo N bond trans to the alkylidene unit are
essential for making this ligand interchange possible. In case
of complex 7, the decomplexation was performed at 60–808C
to avoid racemization of the enantiopure biaryl moiety.
The possibility to remove the phenanthroline (bipyridine)
unit from adducts 2, 3, 5, and 7 without compromising the
reactive metal core distinguishes the current method from
previous attempts to stabilize high valent alkylidene catalysts
with the aid of external donor ligands. Specifically, complex-
ation of Schrock alkylidenes with hydrotris(1-pyrazolyl)bo-
rate or derivatives thereof is known to afford indefinitely air
stable adducts. However, treatment with Lewis acids such as
AlCl3 did not cleanly regenerate the parent complexes but
rather produced mixtures containing one or even more than
one structurally undefined new species of low catalytic
competence.[18–20]
In striking contrast, the decomplexation of the phenathro-
line or bipyridine ligand from 2 or 3, respectively, released the
intact parent tetracoordinate molybdenum alkylidene 1 as
judged by NMR spectroscopy; its excellent reactivity was
found uncompromised by the presence of the precipitated
yellow bipyridine·ZnCl2 or phenanthroline·ZnCl2 that need
not be filtered off.[17] As expected for complex 1 as the active
principle, all chosen test reactions shown in Table 1 were high-
yielding under mild conditions.[21,22] This includes the forma-
tion of sterically hindered and even tetrasubstituted products
at room temperature, the cyclization of electronically disfa-
vored alkenes (vinylsilane, enol ether, enoate), the smooth
conversion of an azide-containing substrate (which is
destroyed by Grubbs-type catalysts bearing R3P ligands) to
an immediate precursor of the protein kinase inhibitor
balanol (entry 8),[23] as well as a desymmetrization reaction
(entry 11) and a kinetic resolution (entry 12) catalyzed by the
chiral complex 7 activated with ZnCl2. We hence conclude
that our new method combines the convenience of handling
of a crystalline and bench-stable precatalyst with the benefits
of a well defined active species of proven versatility. It is
hoped that this approach will foster the use of the remarkably
powerful Schrock alkylidenes and fertilize further investiga-
tions into metathesis reactions using non-noble transition
metal catalysts in general.
Figure 1. Structure of the bipyridine adduct 3 in the solid state.[14] The
structures of the analogous phenanthroline complexes 2 and 5b are
contained in the Supporting Information.
itself (1.9361(12) ꢀ) falls in the normal range and the
neophylidene group shows the expected syn conformation
(orientation toward the imido substituent).[1,2] The overall
structures of the related 1,10-phenanthroline complexes 2 and
5b (Supporting Information) as well as of the chiral bipy-
ridine adduct 7 (Figure 2) in the solid state are largely similar
in that they exhibit distorted octahedral coordination geo-
metries, unequal distances between the metal center and the
two inequivalent N atoms of the chelating donor ligand, as
well as syn-oriented molybdenum alkylidene units.[14]
In contrast to the known adducts of Schrock alkylidenes
with various monodentate donor ligands (ethers, phosphines,
Figure 2. Structure of complex 7 in the solid state.[14] Selected bond
length [ꢁ] and angles [8]: Mo1–N3 1.7626(16), Mo1–C11 1.967(2),
Mo1–N1 2.2561(17), Mo1–N2 2.3352(17), N3-Mo1-O2 169.57(7), C11-
Mo1-N2 168.12(7), Mo1-N3-C45 176.26(16).
Received: March 22, 2011
Published online: July 1, 2011
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[3] a) R. R. Schrock, A. H. Hoveyda, Angew. Chem. 2003, 115,
4740 – 4782; Angew. Chem. Int. Ed. 2003, 42, 4592 – 4633;
b) R. R. Schrock, Top. Organomet. Chem. 1999, 1, 1 – 36.
[4] For an early instructive example from this laboratory, see: A.
Fꢂrstner, K. Langemann, J. Org. Chem. 1996, 61, 8746 – 8749.
[5] a) A. H. Hoveyda, S. J. Malcolmson, S. J. Meek, A. R. Zhugralin,
Angew. Chem. 2010, 122, 38 – 49; Angew. Chem. Int. Ed. 2010, 49,
34 – 44; b) S. J. Malcolmson, S. J. Meek, E. S. Sattely, R. R.
Schrock, A. H. Hoveyda, Nature 2008, 456, 933 – 937.
Table 1: RCM using precatalyst 2 (5 mol%) activated with ZnCl2
(5 mol%); E=COOEt.[a]
Entry Substrate
t
Product
Yield [%]
1
10 min
98
2
12 h
94
[6] a) I. Ibrahem, M. Yu, R. R. Schrock, A. H. Hoveyda, J. Am.
Chem. Soc. 2009, 131, 3844 – 3845; b) A. J. Jiang, Y. Zhao, R. R.
Schrock, A. H. Hoveyda, J. Am. Chem. Soc. 2009, 131, 16630 –
16631; c) M. M. Flook, A. J. Jiang, R. R. Schrock, P. Mꢂller,
A. H. Hoveyda, J. Am. Chem. Soc. 2009, 131, 7962 – 7963; d) S. J.
Meek, R. V. OꢁBrien, J. Llaveria, R. R. Schrock, A. H. Hoveyda,
Nature 2011, 471, 461 – 466.
3
4
5
12 h
12 h
3 h
95, R=tBu
98, R=Ph
93, R=COOEt[b]
[7] a) R. H. Grubbs, Angew. Chem. 2006, 118, 3845 – 3850; Angew.
Chem. Int. Ed. 2006, 45, 3760 – 3765; b) G. C. Vougioukalakis,
R. H. Grubbs, Chem. Rev. 2010, 110, 1746 – 1787; c) C. Samojło-
wicz, M. Bieniek, K. Grela, Chem. Rev. 2009, 109, 3708 – 3742.
[8] J. Heppekausen, R. Stade, R. Goddard, A. Fꢂrstner, J. Am.
Chem. Soc. 2010, 132, 11045 – 11057.
6
7
12 h
1 h
95
96
[9] a) V. Hickmann, M. Alcarazo, A. Fꢂrstner, J. Am. Chem. Soc.
2010, 132, 11042 – 11044; b) K. Micoine, A. Fꢂrstner, J. Am.
Chem. Soc. 2010, 132, 14064 – 14066.
[10] a) To the best of our knowledge, a single example of a related
2,2’-bipyridine adduct was described in the literature; specifi-
8
9
1 h
92[c]
85
=
cally, the methylidene complex [Mo( CH2)(NAr)(ORF6)2]·bipy
was found stable enough for isolation in pure form (ORF6
=
12 h
OC(Me)(CF3)2; Ar= 2,6-diisopropylphenyl), see: H. H. Fox, J.-
K. Lee, L. Y. Park, R. R. Schrock, Organometallics 1993, 12,
759 – 768; b) for a VIII – alkylidene(bipyridine) complex, see:
U. J. Kilgore, C. A. Sengelaub, M. Pink, A. R. Fout, D. J.
Mindiola, Angew. Chem. 2008, 120, 3829 – 3832; Angew. Chem.
Int. Ed. 2008, 47, 3769 – 3772; c) CrIII – alkylidenes react irrever-
sibly with bipyridine, with dearomatization of one of the
heteroarene rings, see: S. Leelasubcharoen, K.-C. Lam, T. E.
Concolino, A. L. Rheingold, K. H. Theopold, Organometallics
2001, 20, 182 – 187.
10
11
1 h
6 h
93
85 (90% ee)[d]
[11] K. M. Wampler, R. R. Schrock, A. S. Hock, Organometallics
2007, 26, 6674 – 6680.
12
1 h
[e]
[12] J. B. Alexander, D. S. La, D. R. Cefalo, A. H. Hoveyda, R. R.
Schrock, J. Am. Chem. Soc. 1998, 120, 4041 – 4042.
[13] W. A. Nugent, J. M. Mayer, Metal – Ligand Multiple Bonds,
Wiley, New York, 1988.
[14] The anisotropic displacement parameters are drawn at the 50%
probability level; hydrogen atoms are omitted for clarity. The
structures of complexes 2 and 5b are depicted in the Supporting
Information. CCDC 816986 (2), 816985 (3), 816984 (5b), and
818215 (7) contain the supplementary crystallographic data for
this paper. These data can be obtained free of charge from The
Cambridge Crystallographic Data Centre via www.ccdc.cam.ac.
uk/data_request/cif.
[a] Unless stated otherwise, the precatalyst was activated by reaction
with ZnCl2 in toluene at 1008C for 30 min; the subsequent RCM
reactions were then performed at ambient temperature. [b] The RCM was
performed at 508C. [c] In CH2Cl2 at reflux. [d] Using precatalyst 7
activated with ZnCl2 in toluene at 808C. [e] Using precatalyst 7 activated
with ZnCl2 in toluene at 658C; at 72% conversion (determined by NMR
spectroscopy using dodecane as internal standard), the recovered
substrate (27%) showed an ee of 99%, and the product (33%) had an ee
of 70%.
[15] R. R. Schrock, W. E. Crowe, G. C. Bazan, M. DiMare, M. B.
OꢁRegan, M. H. Schofield, Organometallics 1991, 10, 1832 –
1843.
[16] A sensitive probe is the syn/anti isomerization of the alkylidene
unit, which can occur only if the ligation is reversible, cf.
Ref. [15].
Keywords: alkene metathesis · alkylidene complexes ·
molybdenum · precatalysts
.
[17] The formation of the corresponding ZnII–phenanthroline or
ZnII–bipyridine adduct was confirmed by mass spectrometry. For
a direct comparison of the NMR spectra of the complex released
from adduct 3 with the aid of ZnCl2 with the spectrum of
authentic 1, see the Supporting Information.
[18] a) L. L. Blosch, K. Abboud, J. M. Boncella, J. Am. Chem. Soc.
1991, 113, 7066 – 7068; b) L. L. Blosch, A. S. Gamble, K.
Abboud, J. M. Boncella, Organometallics 1992, 11, 2342 – 2344;
[1] a) R. R. Schrock, J. S. Murdzek, G. C. Bazan, J. Robbins, M.
DiMare, M. OꢁRegan, J. Am. Chem. Soc. 1990, 112, 3875 – 3886;
b) J. S. Murdzek, R. R. Schrock, Organometallics 1987, 6, 1373 –
1374.
[2] a) R. R. Schrock, Angew. Chem. 2006, 118, 3832 – 3844; Angew.
Chem. Int. Ed. 2006, 45, 3748 – 3759; b) R. R. Schrock, Chem.
Rev. 2009, 109, 3211 – 3226; c) R. R. Schrock, Chem. Rev. 2002,
102, 145 – 180.
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c) A. S. Gamble, J. M. Boncella, Organometallics 1993, 12, 2814 –
2819; d) W. M. Vaughan, K. A. Abboud, J. M. Boncella, J.
Organomet. Chem. 1995, 485, 37 – 43.
following and literature cited: a) M. T. Youinou, J. Kress, J.
Fischer, A. Aguero, J. A. Osborn, J. Am. Chem. Soc. 1988, 110,
1488 – 1493; b) J. H. Wengrovius, R. R. Schrock, Organometal-
lics 1982, 1, 148 – 155.
[19] Even though some of these in situ generated mixtures were
reported to effect ring opening metathesis polymerization, the
activity in acyclic diene polymerization was low even at elevated
temperature, cf. Ref. [18].
[20] For pioneering structural investigations on the activation of
metathesis precatalysts with the aid of Lewis acids, see the
[21] Within experimental error, the yields are identical with those
obtained with authentic 1 under the same conditions.
[22] T. A. Kirkland, R. H. Grubbs, J. Org. Chem. 1997, 62, 7310 –
7318.
[23] A. Fꢂrstner, O. R. Thiel, J. Org. Chem. 2000, 65, 1738 – 1742.
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