An investigation into oxo analogues of molybdenum olefin metathesis complexes as epoxidation catalysts for alkenes

Article abstract of DOI:10.1016/j.tetlet.2009.07.011

The oxo-imido molybdenum complex 2a is an effective catalyst at low catalyst loadings (0.5 mol % or below) for the epoxidation of a range of alkenes with ^tBuOOH in PhMe at 90 °C. Reactions are complete in less than 4 h and the products are isolated in high yields. The catalytic system is chemoselective for the epoxidation of electron-rich alkenes and allylic alcohols.

Full text of DOI:10.1016/j.tetlet.2009.07.011

Tetrahedron Letters 50 (2009) 5344–5346
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Tetrahedron Letters
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An investigation into oxo analogues of molybdenum olefin metathesis
complexes as epoxidation catalysts for alkenes
b
c
b
James C. Anderson a, , Neil M. Smith , Michelle Robertson , Mark S. Scott
*
a Department of Chemistry, University College London, 20 Gower Street, London WC1H 0AJ, UK
b GlaxoSmithKline Research and Development Limited, Gunnels Wood Road, Stevenage, Hertfordshire SG1 2NY, UK
c School of Chemistry, University of Nottingham, Nottingham NG7 2RD, UK
a r t i c l e i n f o
a b s t r a c t
Article history:
The oxo-imido molybdenum complex 2a is an effective catalyst at low catalyst loadings (0.5 mol % or
below) for the epoxidation of a range of alkenes with BuOOH in PhMe at 90 °C. Reactions are complete
in less than 4 h and the products are isolated in high yields. The catalytic system is chemoselective for the
epoxidation of electron-rich alkenes and allylic alcohols.
t
Received 8 May 2009
Revised 23 June 2009
Accepted 3 July 2009
Available online 9 July 2009
Ó 2009 Elsevier Ltd. All rights reserved.
Metal-catalysed olefin epoxidation has received interest from
both academic and industrial research laboratories because epox-
ides are important building blocks in organic synthesis and poly-
mer science.1 Although numerous procedures have been
developed,2 there is still a need for the development of new cata-
lysts that may uncover a more detailed understanding of oxidation
pathways and inform the design of more efficient catalytic sys-
tems. Since the first example of a molybdenum oxo complex cata-
lysing the epoxidation of alkenes with peroxides such as organic
hydroperoxides and hydrogen peroxide,3 a variety of different
complexes have been developed.4–6 It has been reported that the
mixed oxo-imido complex 1 epoxidised cis-cyclooctene,7 but was
not investigated further due to the instability of the catalyst to
the reaction conditions (PhMe, 55 °C). Due to the similarity be-
tween this complex and our own oxo analogues of molybdenum
olefin metathesis catalysts 2,8 we chose to investigate the ther-
mally more stable complex 2a as a catalyst for the epoxidation of
a broad range of substrate alkenes (Fig. 1).
The scope of the reaction was examined using the optimised
conditions (Table 1).11 The epoxidation of trans-stilbene, cis-stil-
bene, styrene, cis-cyclooctene and decene showed complete con-
version by TLC or HPLC (entries 1–5). The isolated yields were
high, except for the reactive styrene oxide. It is noteworthy that
the epoxidation of cis-stilbene generated only cis-epoxide: no trans
product was detected. Functionalised alkenes were investigated to
probe the limitations of the catalyst system. Cyclohexenol (entry 6)
underwent directed epoxidation to give the cis-epoxide as the sole
product isolated in 87% yield, indicating hydrogen bonding or coor-
dination of the hydroxy group to the catalyst. This is an unusual
feature of molybdenum oxo catalysts which has not been com-
monly investigated.4–6 This directing effect was supported by the
regiospecific epoxidation of geraniol (entry 9) in 96% isolated yield.
Epoxidation of geraniol acetate (entry 10) indicates, that in the ab-
sence of a coordinating group, the electronic character of the com-
peting alkenes dictates the regiochemistry to give a 72% isolated
yield of the dimethyl epoxide. A 23% yield of the bis-epoxide was
also isolated with no mono-epoxidation of the allylic acetate de-
tected. However, the limitations of the present catalyst 2a and
reaction conditions are clear with limonene (entry 7) where a mod-
erate 58% yield of the most substituted mono epoxide was isolated.
Initial investigation involved the optimisation of the epoxida-
tion of trans-stilbene with complex 2a using the conditions origi-
nally described for the epoxidation of cis-cyclooctene with 1.7
These were essentially those of Sharpless,9 namely tBuOOH
(2 equiv), 1 (0.4 mol %) and Na2HPO4 (1 mol %) in PhMe at 55 °C.
Consistent and high yielding results for the epoxidation were ob-
tBu
t
tained with catalyst 2a with BuOOH (3 equiv) and 2a (0.5 mol %)
O
R
NtBu
in PhMe at 90 °C. Significant differences from the original literature
example with 1 were that catalyst 2a was active at a higher tem-
perature which ensured efficient conversion and the redundant
use of Na2HPO4 which seemed to retard the reaction.10
tBu
O
N
NtBu
N
Mo
O
R
R
O
O
Mo
N
O
tBu
1
R
i
2a
2b
R= Pr
R=Me
tBu
Figure 1.
* Corresponding author. Tel.: +44 115 951 4194; fax: +44 115 951 3564.
E-mail address: j.c.anderson@ucl.ac.uk (J.C. Anderson).
0040-4039/$ - see front matter Ó 2009 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetlet.2009.07.011

J. C. Anderson et al. / Tetrahedron Letters 50 (2009) 5344–5346
5345
Table 1
To illustrate the effectiveness of the catalytic system, a larger
scale (40 mmol) epoxidation of trans-stilbene was investigated
(Scheme 1). The catalyst loading was reduced from 0.5 mol % to
0.04 mol %, the reaction was monitored by HPLC and the product
epoxide was purified by recrystallisation from petroleum ether to
give an isolated yield of 68%. This represents a substrate to catalyst
loading of 2500:1 and potentially this may be reduced further as the
conversion by HPLC was high. This is testament to the thermal sta-
bility and extremely high reactivity of this particular molybdenum
oxo catalyst compared to many others described in the literature.4–6
Similar molybdenum-catalysed epoxidations are known to pro-
ceed via oxo-, peroxo- or peroxide metal intermediates and the
efficiency of the oxygen transfer step is dramatically influenced
by the coordination environment around the metal centre. Coordi-
nation of chiral ligands has not often led to efficient asymmetric
catalysts due, in part, to the molybdenum complex being di-oxo
or di-peroxo and thus being able to present two possible electro-
philic oxygen atoms to the substrate alkene. The mixed oxo-imido
complex 2, which possesses just one oxygen ligand, could be a
good candidate for development of an asymmetric catalyst by
replacement of the phenoxide ligands with chiral alcohols or a chi-
ral diol. In order to probe whether the mixed oxo-imido ligand set
may be beneficial for asymmetric catalysis we tested the analogous
di-oxo complex MoO2(2,6-Me2C6H3O)2py2 (3)12 and 2b for com-
parison purposes under our reaction conditions.13 The rate of epox-
idation of cis-stilbene was compared by HPLC (Fig. 2) and was
found to be identical for both complexes 2b and 3. This could mean
that each catalyst is converted into the same active di-oxo/di-per-
oxo oxidant. Conversely, the comparison may not be subtle enough
to differentiate between an oxo-peroxo or imido-peroxo ligand set.
Attempted isolation of 2b (or 2a in Table 1) after the reactions was
unsuccessful and led to degradation of the complex. Although this
rate comparison study was inconclusive we believe that the mixed
oxo-imido molybdenum complexes 2 are still attractive for inves-
tigation of an asymmetric process.
MoO(NtBu)(2,6-iPr2C6H3O)2py (2a)-catalysed epoxidation of alkenesa
Entry
1
Alkene
Product
Yieldb (%)
85 (99)c
Ph
Ph
O
Ph
Ph
Ph
Ph
O
2
3
99 (99)c
Ph
Ph
Ph
O
50
Ph
O
4
98d
nOct
O
nOct
5
80
O
6
87
OH
OH
O
O
58
26
7e
O
O
The mixed oxo-imido complex 2a has been shown to be a highly
reactive catalyst (down to 0.04% at least) and thermally stable for
8
9f
—
—
OEt
t
the epoxidation of a wide range of alkenes with BuOOH. The cat-
alytic system is susceptible to direction by a pendant hydroxy
96
72
2a
(0.04 mol%),
OH
OH
tBuOOH (3 equiv)
O
O
Ph
O
Ph
Ph
97% HPLC
PhMe, 90 °C, 20 h
Ph
OAc
O
O
10g
68% (recrystallised from
petroleum ether)
OAc
OAc
23
99
Scheme 1. Epoxidation of trans-stilbene (40 mmol) with 2a (0.04 mol %).
O
O
11
100
90
80
70
60
50
40
OMe
OMe
O
a
Alkene (4.0 mmol), 2a (0.02 mmol) and tBuOOH (12.1 mmol) in PhMe (7.4 mL),
90 °C, 1–4 h.
b
c
d
e
f
Isolated yield.
Yield determined by HPLC.
Conversion determined by 1H NMR.
1.2 equiv tBuOOH.
30
20
10
0
3
2.0 equiv tBuOOH.
2b
g
1.2 equiv tBuOOH.
0
50
100
150
200
Time (min)
Here again, no mono terminal epoxide was isolated. The epoxida-
tion system is electrophilic in nature as evidenced by the regiose-
lective epoxidation of methyl geranate (entry 11) and no
epoxidation was observed for the electronically deactivated ethyl
trans-cinnamate (entry 8).
Figure 2. Time course of MoO(NtBu)(2,6-Me2C6H3O)2py (2b) and MoO2(2,6-
Me2C6H3O)2py2 (3) catalysed epoxidation of cis-stilbene. Conditions: alkene
(4.0 mmol), 2a (0.02 mmol) and tBuOOH (12.1 mmol) in PhMe (7.4 mL), 90 °C, 1–
4 h.

5346
J. C. Anderson et al. / Tetrahedron Letters 50 (2009) 5344–5346
(c) Brito, J. A.; Teruel, H.; Muller, G.; Massou, S.; Gómez, M. Inorg. Chim. Acta
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a,b-unsaturated esters, showing
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Bencze, E.; Herdtweck, E.; Prazeres, A.; Santos, A. M.; Calhorda, M. J.; Romão, C.
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chemoselectivity for electron-rich alkenes. Work is ongoing to elu-
cidate the catalytically active species and chemo- and enantiose-
lective variants of this catalytic system are under investigation.
Acknowledgements
ˇ
79; (i) Petrovski, Z.; Pillinger, M.; Valente, A. A.; Gonçalves, I. S.; Hazell, A.;
We are grateful to Dr. W. B. Cross for a preliminary reaction and
the EPSRC and GlaxoSmithKline for funding.
Romão, C. C. J. Mol. Catal. A: Chem. 2005, 227, 67.
6. For examples of chiral molybdenum epoxidation catalysts, see: (a) Abrantes,
M.; Sakthievel, A.; Romão, C. C.; Kühn, F. E. J. Organomet. Chem. 2006, 691, 3137;
(b) Jain, K. R.; Herrmann, W. A.; Kühn, F. E. Coord. Chem. Rev. 2008, 252, 556; (c)
Barlan, A. U.; Basak, A.; Yamamoto, H. Angew. Chem., Int. Ed. 2006, 45, 5849; (d)
Burke, A. J. Coord. Chem. Rev. 2008, 252, 170; (e) Zhao, J.; Herdtweck, E.; Kühn, F.
E. J. Organomet. Chem. 2006, 691, 2199.
7. Rammauth, R.; Al-Juaid, S.; Motevalli, M.; Parkin, B. C.; Sullivan, A. C. Inorg.
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suggesting that it minimised by-product formation. See Ref. 9a.
11. To a solution of the alkene (4.0 mmol) and 2a (0.02 mmol, 0.5 mol %) in PhMe
(7.5 mL) under an argon atmosphere at rt was slowly added tBuOOH
(12.1 mmol of a 5.5 M solution in decane, 3.0 equiv). The reaction mixture
was heated to 90 °C and monitored by TLC or HPLC until the starting material
had been consumed, which was less than 4 h for all the examples studied. The
reaction mixture was cooled to rt and the solvent removed under vacuum to
obtain a residue. Purification by silica gel column chromatography gave pure
epoxides that possessed identical physical and spectroscopic properties to
those reported.
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identical yield of cis-stilbene oxide as 2a.