Bidentate carbenoid ester coordination in ruthenium(II) Schiff-base complexes leading to excellent levels of diastereo- and enantioselectivity in catalytic alkene cyclopropanation

Article abstract of DOI:10.1039/b104964j

Exceptionally high stereoselectivity (ee ≤ 98%, dr ≤ 99:1) in the cyclopropanation of alkenes with ethyl diazoacetate using a non-planar ruthenium(II) Schiff-base precatalyst is a result of η²C, O binding of the carbenoid ester intermediate, according to DFT calculations.

Full text of DOI:10.1039/b104964j

Bidentate carbenoid ester coordination in ruthenium(II) Schiff-base
complexes leading to excellent levels of diastereo- and
enantioselectivity in catalytic alkene cyclopropanation†
Ian J. Munslow, Kevin M. Gillespie, Robert J. Deeth and Peter Scott*
Department of Chemistry, University of Warwick, Coventry, UK CV4 7AL.
E-mail: peter.scott@warwick.ac.uk
Received (in Cambridge, UK) 5th June 2001, Accepted 12th July 2001
First published as an Advance Article on the web 14th August 2001
Exceptionally high stereoselectivity (ee @ 98%, dr @ 99+1) in
the cyclopropanation of alkenes with ethyl diazoacetate
using a non-planar ruthenium(II) Schiff-base precatalyst is a
result of h2C,O binding of the carbenoid ester intermediate,
according to DFT calculations.
The design of selective methods for the catalytic enantiose-
lective synthesis of cyclopropanes remains of great interest to
organic chemists, not least because of the importance of the
compounds in biological and medicinal chemistry.1 The
asymmetric addition of carbenes to electron rich alkenes2
(alkene cyclopropanation) represents a conceptually simple
approach,3 but typical reactions, such as that of styrenes with a–
diazoacetates in the presence of a chiral metal catalyst, give a
total of six organic products (Scheme 1).
Chemoselectivity for cyclopropanes over carbene dimerisa-
tion products (diethyl malonate and fumarate) is achieved
through use of an excess of alkene and slow addition of the
carbene source e.g. ethyl diazoacetate (EDA) to the reaction
mixture.4,5 For trans-selective catalysts, excellent enantiomeric
excesses have been obtained,6 but most exhibit only moderate
trans/cis- i.e. diastereoselectivity. For example, Evans’ bis(ox-
azoline) copper system gave 99% ee in the trans product which
was formed with a dr of 73+27.6 This and other results are
consistent with Pfaltz’s analysis that the cis/trans selectivity for
a given metal depends almost exclusively on the structure of the
alkene and diazo compound; the effect of the ligand is relatively
unimportant.7 Correspondingly, the use of bulkier diazo ester
substituents such as tert-butyl and 2,6-di-tert-butyl-4-methyl-
phenol leads to much higher diastereoselectivities.6,8,9 An
exception here is found in Che’s D4-symmetric Ru porphyrin
system (dr 97+3, ee 98% at 240 °C) where the four sterically-
demanding chiral substituents strongly orient alkene ap-
proach.10 Highly cis selective catalysts based on Co and Ru
using tert-butyl diazoacetate have recently been reported (e.g.
dr 7+93 and ee 99%).11
that unlike salen-derived ligands, the system L in its early
transition metal complexes gives the a-cis topology I or
occasionally the b-cis structure II;13 both arrangements dictate
that the co-ligands X are placed in mutually cis coordination
sites. This has important consequences for alkene cyclopropa-
nation by the complexes M = Ru as described herein.
The reaction of Na2Ln with [{RuCl(m-Cl)(h-C6H6)}2] in
acetonitrile gave the RuII complexes of ligands Ln in high
yield.
The molecular structure of one example b-cis-
[RuL1(CH3CN)2] is shown in Fig. 1.† This, and analogous
complexes of L2 and L3 retain the b-cis structure II in solution
as evidenced by NMR spectroscopy.
We have been interested in the use of biaryldiimine
complexes in enantioselective catalysis,12 and have discovered
Scheme 1 Products typically formed in metal catalysed cyclopropanation
via intermolecular carbene transfer to alkene.
† Electronic supplementary information (ESI) available: experimental and
2
theoretical details, structures of [RuL1(CH3CN)2] and [RuL1(h -
CHCO2Et)] (.pdb). CCDC 167600. See http://www.rsc.org/suppdata/cc/b1/
b104964j/
Fig. 1 Molecular structure of the precatalyst b-cis-[RuL1(CH3CN)2].
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Chem. Commun., 2001, 1638–1639
This journal is © The Royal Society of Chemistry 2001
DOI: 10.1039/b104964j

Table
1 Enantioselective cyclopropanation catalysed by (R)-b-cis-
[RuL1(CH3CN)2]a
Entry
1
Product
Yield/(%)b
92
dr/(%)
ee/(%)c
98
99+1
2
3
88
94
99+1
98+2
97
95
2
Fig. 2 Calculated structure of the carbene catalyst [RuL1(h -CHCO2Et)]
showing the preferred orientation of approach of styrene.
4
5
90
89
96+4
96+4
86
86
P. S. wishes to thank EPSRC for a postdoctoral fellowship
(K. M. G.) and Pfizer Ltd for a CASE award (I. J. M.). R. J. D.
acknowledges the use of the EPSRC UK Computational
Chemistry Facility.
Notes and references
6
80
—
91
‡ This complex also efficiently catalyses the intramolecular cyclopropana-
tion/cylisation of a range of allylic diazoacetates. For example, trans-hex-
2-enyl and geranyl diazoacetates were converted to the corresponding
oxabicyclohexanones (entries 6 and 7) in a similar manner to Doyle et al.,3
with the exception that slow addition of substrate was not required and the
reaction proceeded at rt in under 2 h.
7
98
—
85
§ Attenuated selectivity in polar solvents, particularly for more electron rich
alkenes, suggests significant polarity in the transition state. This will be
investigated by Hammett methods. Preliminary kinetic experiments have
indicated that the reaction is first order in catalyst.
¶ The (S)-catalyst shown in Fig. 2 gives rise to 1S-2S cyclopropanes, hence
(S)-b-cis-[RuL1(CH3CN)2] used in the experimental study is predicted to
yield 1R-2R isomers (Table 1).
a Entries 1–5; 5 mol% of (R)-b-cis-[RuLn(CH3CN)2] in toluene, 4/5 equiv.
of styrene, 2 h at rt. b Isolated yield after flash chromatography (yield based
on EDA for entries 1–5). c Absolute configuration of trans isomer (1R,2R)
by comparison of optical rotations with literature values (ref. 15) for entries
1–5.
1 J. Salaün, Top. Curr. Chem., 2000, 207, 1; J. Salaun and M. S. Baird,
Curr. Med. Chem., 1995, 2, 511; C. J. Suckling, Angew. Chem., Int. Ed.,
1988, 27, 537.
2 For cyclopropanation of electron poor alkenes see V. K. Aggarwal,
H. W. Smith, G. Hynd, R. V. H. Jones, R. Fieldhouse and S. E. Spey,
J. Chem. Soc., Perkin Trans. 1, 2000, 3267; A.-H. Li, L.-X. Dai and
V. K. Aggarwal, Chem. Rev., 1997, 97, 2341.
3 M. P. Doyle and D. C. Forbes, Chem. Rev., 1998, 98, 911.
4 M. P. Doyle, D. V. Leusen and W. H. Tamblyn, Synthesis, 1981, 787.
5 H.-L. Kwong, L.-S. Cheng, W. -S. Lee, W.-L. Wong and W.-T. Wong,
Eur. J. Inorg. Chem., 2000, 1997; M. M. Díaz-Requejo, T. R.
Belderrain, M. C. Nicasio, F. Prieto and P. J. Pérez, Organometallics,
1999, 18, 2601.
6 D. A. Evans, K. A. Woerpel, M. M. Hinman and M. M. Faul, J. Am.
Chem. Soc., 1991, 113, 726.
7 H. Fritschi, U. Leutenegger and A. Pfaltz, Helv. Chim. Acta., 1988, 71,
1553.
8 T. Fukuda and T. Katsuki, Tetrahedron, 1997, 53, 7201; S.-B. Par, N.
Sakata and H. Nishiyama, Chem. Eur. J., 1996, 2, 303.
9 R. Rios, J. Liang, M. M.-C. Lo and G. C. Fu, Chem. Commun., 2000,
377.
10 C.-M. Che, J.-S. Huang, F.-W. Lee, Y. Li, T.-S. Lai, H.-L. Kwong. P.-F.
Teng, W.-S. Lee W.-C. Lo, S.-M. Peng and Z.-Y. Zhou, J. Am. Chem.
Soc., 2001, 123, 4119.
11 T. Uchida, R. Irie and T. Katsuki, Tetrahedron, 2000, 56, 3501; T.
Niimi, T. Uchida, R. Irie and T. Katsuki, Tetrahedron Lett., 2000, 41,
3647.
12 C. J. Sanders, K. M. Gillespie, D. Bell and P. Scott, J. Am. Chem. Soc.,
2000, 122, 7132; K. M. Gillespie, E. J. Crust, R. J. Deeth and P. Scott,
Chem. Commun., 2001, 785.
13 P. R. Woodman, N. W. Alcock, I. J. Munslow, C. J. Sanders and P.
Scott, J. Chem. Soc., Dalton Trans., 2000, 3340; P. R. Woodman, I. J.
Munslow, P. B. Hitchcock and P. Scott, J. Chem. Soc., Dalton Trans.,
1999, 4069; P. R. Woodman, C. J. Sanders, N. W. Alcock, P. B.
Hitchcock and P. Scott, New J. Chem., 1999, 23, 815.
14 M. Brookhart, Y. Liu, E. W. Goldman, D. A. Timmers and G. D.
Williams, J. Am. Chem. Soc., 1991, 113, 927.
The results of addition of EDA over 2 h to solutions of
styrenes at rt in the presence of pure precatalyst (R)-b-cis-
[RuL1(CH3CN)2] are summarised in Table 1 (entries 1–5).‡ The
chemoselectivity (yield), trans+cis ratios (dr) and ee are
arguably the best yet attained.10,11 The ligand L1 appears to be
close to optimal for the cyclopropanation of styrenes; prelimi-
nary experiments with the bulky system L2 and the electron
withdrawing L3 gave significantly lower selectivities. Mecha-
nistic details for the catalytic reaction are currently under
investigation.§
The selectivity determining step in alkene cyclopropanation
involves the transfer of a metal bound carbene to the substrate,14
and we set out to investigate this crucial step for the current
system using Density Functional Theory (DFT) calculations. A
fully optimised DFT structure of the precatalyst b-cis-
[RuL1(CH3CN)2] was found to be virtually superimposable on
the molecular structure shown in Fig. 1. Minimisation of a
structure arising from the removal of the CH3CN groups and
addition of the carbene derived from EDA (i.e. :CH-CO2Et) led
2
spontaneously to formation of a chelate, reminiscent of h -
carboxylate, with both carbene C atom and carbonyl oxygen
atom bound to Ru (Fig. 2). This structure with the carbene C
atom trans to phenolate is ca. 30 kJ mol21 more stable than that
with the carbene trans to imine; an observation in accord with
the expected order of trans influence of the two groups (N >
O).
Hence the electronically controlled placement of the carbene
trans to phenolate and the subsequent ester binding determines
which diastereomeric face of the carbenoid is presented to the
incoming alkene. The sense of asymmetric induction is as
predicted by this model.¶ Also as a result of tight binding of the
carbenoid ester, the orientation of approach of the alkene toward
the reaction centre is exceptionally well directed by the chiral
biaryldiimine ligand (Fig. 2); this leads to the high diaster-
eoselectivity observed.
15 A. Nakamura, A. Konishi, R. Tsujitani, M. Kudo and S. Otsuka, J. Am.
Chem. Soc., 1978, 100, 3449.
Chem. Commun., 2001, 1638–1639
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