Manganese catalysed asymmetric cis-dihydroxylation with H2O 2

Article abstract of DOI:10.1039/b808355j

High turnover enantioselective alkene cis-dihydroxylation is achieved with H₂O₂ catalysed by manganese based complexes containing chiral carboxylato ligands. The Royal Society of Chemistry.

Full text of DOI:10.1039/b808355j

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Manganese catalysed asymmetric cis-dihydroxylation with H2O2w
Johannes W. de Boer,ab Wesley R. Browne,a Syuzanna R. Harutyunyan,a
Laura Bini,c Theodora D. Tiemersma-Wegman,a Paul L. Alsters,c Ronald Hagebd
and Ben L. Feringa*a
Received (in Cambridge, UK) 19th May 2008, Accepted 25th June 2008
First published as an Advance Article on the web 17th July 2008
DOI: 10.1039/b808355j
High turnover enantioselective alkene cis-dihydroxylation is
achieved with H2O2 catalysed by manganese based complexes
containing chiral carboxylato ligands.
In our earlier reports6 we described the cis-dihydroxylation
and epoxidation of alkenes with H2O2 catalysed by bis-m-car-
boxylato bridged dinuclear manganese(III) complexes
(i.e. [MnIII2(m-O)(m-RCO2)2(tmtacn)2]2+, where tmtacn is
N,N0,N00-trimethyl-1,4,7-triazacyclononane, Fig. 1). For the
substrate cyclooctene, over 2000 turnovers towards the cis-
diol could be achieved and catalyst loadings below 0.1 mol%
have been used successfully with near complete efficiency in the
consumption of H2O2. The selectivity towards either cis-dihy-
droxylation or epoxidation can be tuned through the carboxy-
lato ligand employed (RCO2ꢀ), e.g. 2,6-dichlorobenzoate or
2-hydroxybenzoate, respectively. The catalyst becomes more
active with increased electron deficiency of the carboxylic acid
and, importantly, the selectivity towards cis-dihydroxylation is
highest with sterically demanding carboxylato ligands.
The central importance of chirality to modern chemistry has
driven the development of asymmetric reactions and especially
enantioselective catalysis.1 Amongst the many catalysed organic
transformations, selective catalytic oxidation, in particular the
cis-dihydroxylation of alkenes, has proven to be challenging
with regard to achieving atom efficiency and selectivity.2
The seminal report3 and subsequent development2,4 of the
osmium catalysed asymmetric cis-dihydroxylation (AD) of
alkenes by Sharpless and co-workers have proven to be
invaluable to synthetic organic chemistry. However, the cost
and toxicity of the osmium based AD systems, prevents their
widespread industrial application.5 This has provided a strong
driving force to the identification and development of eco-
nomically viable and environmentally benign methods based
on first row transition metals and H2O2.
Our identification of carboxylato bridged MnIII2 complexes as
the active catalyst species,6 taken together with the results of
Bolm,9 Sherrington10 and co-workers, where enantiomeric ex-
cesses of up to 60% were achieved for alkene epoxidation using
related manganese complexes based on chiral tmtacn type
ligands,11 prompted us to explore the use of readily available
chiral carboxylic acids in achieving AD.12 Chiral carboxylic
acids hold a distinct advantage over synthetically challenging
chiral versions of the tmtacn ligand in that the catalytically
Recently we have demonstrated that highly efficient and
selective cis-dihydroxylation of alkenes with H2O2 can be
achieved with manganese based catalysts.6 Taken together
with the recent discovery of highly enantioselective AD of,
especially, trans-alkenes by iron(II) based catalysts, by Que and
co-workers, albeit with very low turn over numbers,7 so far
these findings indicate that the goal of high turnover 1st row
transition metal based AD methods may be within reach.
Herein, we describe the development of the first manga-
nese based catalyst system for asymmetric cis-dihydroxylation
(AD) of alkenes with H2O2. With 0.4 mol% catalyst
loading the enantioselective cis-dihydroxylation of 2,20-
dimethylchromene proceeds with full conversion and high
selectivity towards the cis-diol product with enantiomeric
excess of up to 54% and with high turnover.
active bis-m-carboxylato MnIII complex can be formed6 in situ
2
by reduction of 113 {[MnIV2(m-O)3(tmtacn)2]2+} with H2O2 in
the presence of the carboxylic acid of interest, which facilitates
optimising the ee (Fig. 1, ESI Table S1w).
a Stratingh Institute for Chemistry, Faculty of Mathemathics and
Natural Sciences, University of Groningen, Nijenborgh 4, Groningen
9747 AG, The Netherlands. E-mail: b.l.feringa@rug.nl; Fax: +31
50 363 4279
b Rahu Catalytics, Oliver van Noortlaan 120, 3133 AT Vlaardingen,
The Netherlands
c DSM Pharma Products Innovative Synthesis and Catalysis, PO Box
6160, MD Geelen, The Netherlands
d Unilever R&D Vlaardingen, PO Box 114, 3130 AC Vlaardingen
The Netherlands
w Electronic supplementary information (ESI) available: Synthesis
and characterisation of all complexes and compounds, experimental
procedures, NMR analysis, discussion of analysis methods. See DOI:
10.1039/b808355j
Fig. 1 In situ conversion of 1 to [MnIII2(m-O)(m-RCO2)2(tmtacn)2]2+
by reduction with H2O2 in the presence of RCO2H. Complexes 2–6
were prepared independently also (see ESIw).
ꢁc
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Scheme 1 Asymmetric cis-dihydroxylation (AD) of chromene with
H2O2 catalysed by the system 6/Ac-D-Phg.8
A series of twenty four chiral carboxylic acids were selected
(see ESI, Fig. S1w) containing a stereogenic centre a to
the carboxylic acid. The substrate scope6a for the system
1/RCO2H shows that the highest selectivity and activity
towards cis-dihydroxylation are obtained with electron-rich
cis-alkenes and hence the prochiral cis-alkene 2,2-dimethyl-
chromene, one of the more challenging substrates in the
osmium catalysed AD,4 was selected as substrate to identify
chiral carboxylic acids suitable for inducing enantioselectivity
(Scheme 1).
Fig. 2 Enantioselective cis-dihydroxylation of 2,2-dimethylchromene
by 2 (1 mM, 0.4 mol%) and Boc-phenylglycine (62.5 mM, 25 mol%) in
CH3CN–H2O (9:1) at 0 1C. Conversion of substrate as function of
time (filled squares), ee of the cis-diol as function of time (open stars).
Overall, chiral carboxylic acids, which contain a phenyl or
naphthyl group attached directly to the stereogenic carbon atom
show similar ee (13–20%) with substrate conversion generally
higher than 60% (Table S1,w Scheme 2). The N-carbamate
protected amino acids provided an enantiomeric excess of ca.
30% (Table S1w). Those acids lacking an aromatic group at the
stereogenic centre showed good substrate conversion albeit
providing low enantiomeric excess for the cis-diol product.
The cis-diol product is the major product in all cases and the
cis-/trans-diol ratio8 is generally good (typically varying between
2.7 and 4.3, see ESI for detailed discussionw). The highest
cis-/trans-diol ratio (7.0) is observed for (1S)-(+)-ketopinic acid
(Table S1w) and this indicates that steric bulk close to the
carboxylic acid functionality favours cis-dihydroxylation over
the epoxidation of cyclooctene. Thus, based on preliminary
screening, it can be concluded that the system 1/carboxylic acid
is effective for catalytic AD of chromene where the carboxylato
ligand is functionalised with an aromatic group at the stereogenic
carbon atom and that the other atom attached to the stereogenic
carbon is, preferably, a protected amine. The combination of 1
with acetyl protected D-phenylglycine (Ac-D-Phg) provided
the highest substrate conversion (99%) and ee (38%) of the
3R,4R-cis-diol.
Scheme 2 Asymmetric dihydroxylation (AD) of chromene with H2O2
catalysed by the system 1–6/RCO2H.8
m-bis-carboxylato MnIII complexes were formed in situ.
2
[MnIII2(m-O)(m-N-Boc-phenylglycine)2(tmtacn)2]2+ (2) and com-
plexes 3–6 were prepared as described earlier (see ESIw). Almost
complete conversion of 2,2-dimethylchromene was observed and
the corresponding cis-diol was obtained with 37% ee (Table 1,
entry 1). Importantly the ee of the cis-diol remains constant over
the entire course of the reaction (Fig. 2). Decreasing the amount
of Boc-Phg-OH from 25 to 4 mol% resulted in a somewhat lower
yield, however the ee was unaffected (entry 2). The conversion
and ee of the cis-diol product are essentially the same as observed
with in situ formation of 2 from 1/Boc-Phg-OH by pretreatment
with H2O2 (entry 5). As expected Boc-D-Phg-OH in place of Boc-
Phg-OH provides the same enantioselectivity but for the opposite
enantiomer (Table S1w).
With Boc-phenylalanine (Boc-Phe-OH), Boc-D-proline
(Boc-D-Pro-OH) and Boc-alanine (Boc-Ala-OH) and their
respective complexes 3–5 (see ESIw), cis-dihydroxylation of
2,20-dimethylchromene proceeded (Table 1) as with the
complexes formed in situ (Table S2w).15
The AD of 2,2-dimethylchromene with H2O2 catalysed by the
independently prepared and characterised (see ESIw) complex
[MnIII2(m-O)(m-Boc-phenylglycine)2(tmtacn)2]2+ (2, 0.4 mol%)/
Boc-phenylglycine (25 mol%) was examined to confirm that the
Table 1 Manganese catalysed AD of 2,2-dimethylchromenea
Entry
Catalyst/carboxylic acid (mol%)
Conv. (%)b
ee (%) cis-diolcd
cis/transe ratioc
1
2
3
4
5
6
7
8
9
a
2/Boc-Phg (25)
2/Boc-Phg (4)
2/Boc-Phg (4)f
2/—
97
85
41
48
80
0
80
50
75
c
37
36
44
36
35
—
2.5
12h
4.7
d
4.1
5.3
4.3
7.7
1.8
—
1.2
1.4
2.4
1/Boc-Phg (4)g
MnII(ClO4)2ꢂ6H2O/Boc-Phg (25)
3/Boc-Phe (4)
4/Boc-D-Pro (4)
5/Boc-Ala (4)
b
At 0 1C in CH3CN–H2O (9 : 1), see ESI for details.w Determined by GC. Determined by HPLC. Absolute configuration (3S,4S) by comparison
with reported optical rotation.14 e This ratio provides an indirect estimation of the cis-diol/epoxide selectivity of the reaction (see ESIw); the ee of the
trans-diol was in each case o8%. In CH3CN. Catalyst treated with H2O2 prior to addition of substrate (see ESIw). (3R,4R) configuration.
f
g
h
ꢁc
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Table 2 Temperature dependence of the AD of 2,2,-dimethylchromenea
Entry
Catalyst/carboxylic acid (mol%)
Temp. (1C)
ee (%) cis-diol
Conv. (%)
1
2
3
4
5
6
7
8
a
1/Boc-Phg (25)b
2/Boc-Phg (25)
2/Boc-Phg (25)c
1/Ac-D-Phg (25)b
1/Ac-D-Phg (4)d
6/Ac-D-Phg (4)c
6/ Ac-D-Phg (4)e
6/ Ac-D-Phg (4)f
20
0
ꢀ20
20
0
28 (3S,4S)
37 (3S,4S)
47 (3S,4S)
38 (3R,4R)
42(3R,4R)
54 (3R,4R)
50 (3R,4R)
42 (3R,4R)
d
88
97
51
99
80
55
n.d.
n.d.
ꢀ20
0
0
b
c
See procedure A (ESIw). See procedure B (ESIw). Reaction performed in CH3CN/H2O (19 : 1 v/v). Pre-treatment of the catalyst with
e
H2O2. 30% D2O2. 30% H2O2; n.d. not determined.
f
At 0 1C with 6/Ac-D-Phg the cis-diol product was obtained
in 42% isolated yield and 41% ee. The use of D2O/D2O2
facilitated the recording of the 1H NMR spectrum of the
reaction mixture at the end of the reaction. Almost complete
conversion of the alkene substrate was observed and further-
more, only the cis-diol and (a minor amount of the) trans-diol
products were observed (see Fig. S2 ESIw).
eds. E. L. Eliel, S. H. Wilen and M. P. Doyle, Wiley-Interscience,
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The temperature dependence of the enantioselectivity shows an
increase in ee with reduction in temperature (Table 2). For
example, the ee of (3R,4R)-chromene-diol is 38%, 42% and
54% when the reaction catalysed by the system 1/Ac-D-Phg-OH
is performed at 20 1C, 0 1C and ꢀ20 1C, respectively (Table 2,
entries 4, 5 and 6).16 In our earlier report6b we demonstrated
that the activity and the cis-diol/epoxide selectivity of the system
1/CCl3CO2H was unaffected by the use of D2O2/D2O. However,
in the AD of chromene the use of D2O2 with the system
6/Ac-D-Phg-OH results in a significant increase in enantiomeric
excess (from 42 to 50% ee, Table 2, entries 7 and 8).
5 M. Beller, Adv. Synth. Catal., 2004, 346, 107.
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8 In addition to cis-diol, for chromene a significant amount of the
trans-diol product is formed, in all cases with an ee o10%. The
direct formation of trans-diol is unlikely, but instead it is formed
from the epoxide product via two distinct routes, i.e. via epoxida-
tion of the alkene followed by hydrolysis of the epoxide by H2O
directly and via opening of the epoxide by the chiral carboxylic acid
followed by hydrolysis of the intermediate carboxylato ester (see
ESI, Scheme S2).
In conclusion, we have demonstrated the AD of 2,2-dimethyl-
chromene with H2O2 catalysed by dinuclear manganese com-
plexes. The reactivity and selectivity is readily tunable by variation
of the carboxylic acid employed. The preference of the present
[MnIII2(m-O)(m-RCO2)2(tmtacn)2]2+ catalyst systems towards
electron-rich cis-alkenes limits the scope of the system. However,
the high turnover numbers and efficiency achievable, the tunablity
of the system and its use of H2O2 as the terminal oxidant
demonstrate that a sustainable and synthetically useful method
for the 1st row transition metal catalysed AD is now within reach.
The present system constitutes the first manganese based
catalyst for the enantioselective cis-dihydroxylation of alkenes.
Taken together with the recent report of AD by Que and
coworkers7 where iron based catalysts demonstrate activity in
the AD of trans-alkenes, the present system forms an excellent
basis on which to build on a range of selective and economic-
ally and environmentally acceptable 1st row transition metal
catalysed AD methods.
9 C. Bolm, D. Kadereit and M. Valacchi, Synlett, 1997, 687; C.
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¨
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´
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We thank the Dutch Economy, Ecology, Technology
(Grant EETK01106) program for financial support. We thank
Prof. J. Reedijk and Dr J. G. Roelfes for valuable discussions
and suggestions.
14 P. Anastasis and P. E. Brown, J. Chem. Soc., Perkin Trans. 1, 1983,
1431.
15 The combination of Boc-Phg-OH and a MnII salt was not active
under the present conditions.
Notes and references
16 A further decrease in temperature to below ꢀ20 1C results in the
freezing out of the water present in the reaction mixture, which
reduces the activity of the catalyst significantly.
1 Comprehensive asymmetric Catalysis, eds. E. N. Jacobsen, A. Pfaltz
and H. Yamamoto, Springer, 2004, Basic Organic Stereochemistry,
ꢁc
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