Highly active oligomeric (salen)Co catalysts for asymmetric epoxide ring-opening reactions

Full text of DOI:10.1021/ja005867b

J. Am. Chem. Soc. 2001, 123, 2687-2688
2687
Scheme 1. Strategies for Polymerization of C2 Symmetric
Salen Ligands
Highly Active Oligomeric (salen)Co Catalysts for
Asymmetric Epoxide Ring-Opening Reactions
Joseph M. Ready and Eric N. Jacobsen*
Department of Chemistry and Chemical Biology
HarVard UniVersity, Cambridge, Massachusetts 02138
ReceiVed December 9, 2000
Cooperative bimetallic catalysis has been documented in several
recently reported asymmetric epoxide opening reactions that
display second-order kinetic dependence on catalyst, specific
requirements for multiple metal ions, and/or pronounced catalyst
nonlinear effects.1 In such systems, one metal is proposed to serve
as Lewis acid for epoxide activation and another as counterion
for the nucleophile. In this mechanistic context, complexes that
contain multiple metal centers in appropriate relative proximity
and orientation can provide improved reactivity relative to
monometallic catalysts. For example, chiral metal salen complexes
such as 1 are effective catalysts for asymmetric epoxide ring-
opening reactions, and operate by a second-order mechanism.2
Linking these catalysts as dimers3 or to polymeric4 or dendrimeric5
frameworks leads to catalytic systems with similar enantioselec-
tivity and substantially enhanced reactivity relative to 1. The
synthetic utility of multimeric catalysts prepared in this manner
is limited, however, by the inefficiency of their syntheses.6 We
report here new, easily synthesized oligomeric analogues of 1
that exhibit not only remarkably enhanced reactivity, but also
significantly higher enantioselectivity relative to 1.
Scheme 2. Preparation of the Cyclic Oligosalen Catalysts
it was found that oligomerization could be effected cleanly by
condensation of (R,R)-diaminocyclohexane (3) and dialdehyde 4
in solvents such as THF (Scheme 2).8,9 Subsequent metal insertion
and air oxidation in the presence of lutidinium p-toluenesulfonate
(LPTS) afforded a mixture of oligo-(salen)Co(OTs) complexes
(5). Mass spectral (FAB+-TOF) and 13C NMR data indicated the
exclusive formation of cyclic oligomers containing 2-6 metal-
(salen) units.10
Asymmetric hydrolysis of cyclohexene oxide (eq 1) was
selected as a challenging test of the reactivity of 5, as this reaction
has proven to be very difficult to catalyze with monomeric (salen)-
Co complexes.11 At a catalyst loading of 1.5 mol % with respect
The construction of oligomers or polymers consisting of
repeating C2 symmetric salen units would circumvent the problems
associated with the preparation of unsymmetrical salen derivatives
(Scheme 1).7 Extensive studies were carried out to establish the
optimal strategy for oligomerization of C2-symmetric salen units,
with evaluation of not only the two condensation strategies
outlined in Scheme 1, but also of such variables as linker identity,
use of endcaps, and reaction solvent and temperature. Ultimately,
to Co (i.e. 1.5/n mol % with respect to the oligmer mixture 5),12
hydrolysis of cyclohexene oxide was complete within 11 h
providing the corresponding trans-1,2-diol in 94-96% ee. As
reflected by the data in Figure 1, significant enhancements in both
rate and enantioselectivity were observed relative to monomeric
catalysts.
The catalytic asymmetric ring-opening of epoxides with
alcohols as nucleophiles is a second reaction class that has proven
particularly difficult to effect, with no examples reported to date.13
In the context of kinetic resolution of terminal epoxides, alcoholic
(1) (a) Hansen, K. B.; Leighton, J. L.; Jacobsen, E. N. J. Am. Chem. Soc.
1996, 118, 10924-10925. (b) Tokunaga, M.; Larrow, J. F.; Kakiuchi, F.;
Jacobsen. E. N. Science 1997, 277, 936-938. (c) McCleland, B. W.; Nugent,
W. A.; Finn, M. G. J. Org. Chem. 1998, 63, 6656-6666. (d) Matsunaga, S.;
Das, J.; Roels, J.; Vogl, E. M.; Yamamoto, N.; Iida, T.; Yamaguchi, K.;
Shibasaki, M. J. Am. Chem. Soc. 2000, 122, 2252-2260. (e) Schaus, S. E.;
Jacobsen, E. N. Org. Lett. 2000, 2, 1001-1004.
(2) For reviews, see: (a) Jacobsen, E. N.; Wu, M. H. In ComprehensiVe
Asymmetric Catalysis; Jacobsen, E. N., Pfaltz, A., Yamamoto, H., Eds.;
Springer-Verlag: New York, 1999; pp 1309-1326. (b) Jacobsen, E. N. Acc.
Chem. Res. 2000, 33, 421-431.
(8) The importance of chlorine substituents on the linker was established
through studies on the model monomer catalyst 2, which was found to display
reactivity and enantioselectivity similar to 1. Dialdehyde 4 was synthesized
as a mixture of diastereomers in two steps from pimelic acid via the
corresponding R,R′-dichlorodiacid chloride (see Supporting Information).
Harpp, D. N.; Bao, L. Q.; Black, C. J.; Gleason, J. G.; Smith, R. A. J. Org.
Chem. 1975, 40, 3420.
(3) Konsler, R. G.; Karl, J.; Jacobsen, E. N. J. Am. Chem. Soc. 1998, 120,
10780-10781.
(4) Annis, D. A.; Jacobsen, E. N. J. Am. Chem. Soc. 1999, 121, 4147-
4154.
(5) Breinbauer, R.; Jacobsen, E. N. Angew. Chem., Int. Ed. 2000, 39, 3604-
(9) Full experimental details, spectral data for new compounds and ee
determinations are presented in the Supporting Information.
3607.
(6) This inefficiency stems from the absence of local C2 symmetry in the
individual salen units, as present in 1. The condensation of two different
salicylaldehyde derivatives with 1,2-diaminocyclohexane provides a statistical
mixture of desired unsymmetrical and undesired symmetrical salen ligands
that are readily separable only by chromatography.
(7) For recent examples of polymeric catalysts, see: (a) Rossi, P.; Felluga,
F.; Tecilla, P.; Foermaggio, F.; Crisma, M.; Toniolo, C.; Scrimin, P. J. Am.
Chem. Soc. 1999, 121, 6948-6949. (b) Fan, Q.; Ren, C.; Yeung, C.; Hu, W.;
Chan, A. S. C. J. Am. Chem. Soc. 1999, 121, 7407-7408. (c) Yu, H.-B.; Hu,
Q.-S.; Pu, L. J. Am. Chem. Soc. 2000, 122, 6500-6501.
(10) For previous examples of cyclic disalen derivatives, see: (a) Huck,
W. T. S.; van Veggel, F. C. J. M.; Reinhoudt, D. N. Recl. TraV. Chim. Pays-
Bas 1995, 114, 273-276. (b) Li, Z.; Jablonski, C. Chem. Commun. 1999,
1531-1532.
(11) For asymmetric ring-opening of meso epoxides with other oxygen
nucleophiles, see ref 1d and: (a) Jacobsen, E. N.; Kakiuchi, F.; Konsler, R.
G.; Larrow, J. F.; Tokunaga, M. Tetrahedron Lett. 1997, 773-776. (b) Nozaki,
K.; Nakano, K.; Hiyama, T. J. Am. Chem. Soc. 1999, 121, 11008-11009. (c)
Weijers, C. A. G. M. Tetrahedron: Asymmetry 1997, 8, 639-647.
(12) The MW/Co of 5 is independent of n.
10.1021/ja005867b CCC: $20.00 © 2001 American Chemical Society
Published on Web 02/23/2001

2688 J. Am. Chem. Soc., Vol. 123, No. 11, 2001
Communications to the Editor
Table 2. Preparation of R-Aryloxy Alcohols by Kinetic Resolution
of Terminal epoxides with phenols catalyzed by (salen)Co
Complexesa
Co
yield ee
entry
1
R1
R2
catalyst
(mol %)b (%)c (%)d
H
CH2Cl monomer (1c)
oligomer (5)
4.0e
0.25
4.4
0.25
4.0
1.0
8.0
0.5
4.0
96
99
48
99
f
99
99
84
98
n.d.
97
94
98
2
3
4
5
o-O(allyl) CH2Cl 1c
5
1c
5
H
C6H5
Figure 1. Asymmetric hydrolysis of cyclohexene oxide catalyzed by
(salen)Co complexes. Reactions were carried out with [epoxide]0 ) 2.5
M in 1:1 CH3CN:CH2Cl2 at 4 °C. Conversion was determined by GC
analysis relative to an internal standard.
60
89
99
H
c-hexyl 1c
5
n-butyl 1c
5
o-Cl
80g 68
0.8
98
99
Table 1. Kinetic Resolution of Epoxides with Alcohols Catalyzed
by 5a
a Reactions were carried out with [epoxide]0 ) 5 M in TBME (1c)
or CH3CN (5) for 4-24 h unless indicated otherwise. See Supporting
Information for details. b Catalyst loading on a per Co basis relative to
phenol. c Isolated yields based on phenol. d Determined by chiral HPLC
f
or GC analysis. e Reference 17. After 10 d, the reaction had proceeded
Co
yield
(%)c
ee
to 63% conversion of phenol to afford a 2:3 mixture of regioisomeric
R1
R2
(mol %)b
(%)d
products favoring internal attack. g 72 h reaction time.
entry
1
2
3
4
5
6
7
8
9
C6H5
(TMS)CH2
H
2-BrC6H4
4-(OMe)C6H4 (CH2)3CH3
2-(NO2)C6H4
CH2dCH
C6H5
(CH2)3CH3
(CH2)3CH3
(CH2)3CH3
(CH2)3CH3
2.0
0.2
0.1
0.1
2.0
0.5
0.5
2.0
2.0
87
97
96
99
62
98
87
91
95
98
99
94
>99
94
99
97
98
98
epoxides with phenols (Table 2). Use of 5 allows substantial
decreases in catalyst loading and provides improved enantio-
selectivity in many cases (entries 1, 4, and 5). More striking,
perhaps, are the epoxide-phenol combinations that were unre-
active with catalyst 1c, but that provide the R-aryloxy alcohols
in high yield, ee, and regioselectivity in the presence of the
oligosalen catalyst 5 (entries 2 and 3).
(CH2)3CH3
(CH2)3CH3
CH2Cl
C6H5
CH2O(allyl)
Analysis of the addition of o-chlorophenol to (()-1,2-epoxy-
hexane in the presence of 5 revealed a first-order kinetic
dependence on catalyst,16 consistent with an intramolecular ring-
opening event. This stands in contrast to the second-order
dependence observed with monomeric catalysts, and provides a
compelling indication that epoxide ring-opening with 5 takes place
via cooperative reactivity of two (or possibly more)2b metal sites
within the cyclic framework. Whereas the act of oligomerizing
Co(salen) units was expected to lead to catalysts with enhanced
reactivity relative to monomeric analogues, the observed improve-
ments in enantioselectivity were unanticipated. The latter cannot
be ascribed to perturbations to the local coordination environment
of the catalysts, since monomer 2c is effectively identical to 5 in
that respect yet it displays enantioselectivities more akin to those
of 1. Instead, the cyclic architecture of 5 appears to constrain the
salen units in relative orientations that lead to enhanced stereo-
chemical communication in epoxide ring-opening reactions. A
fuller understanding of the origin of this improvement is the focus
of ongoing studies.
a Reactions were carried out with [epoxide]0 ) 5 M in CH3CN for
3-24 h. See Supporting Information for details. b Catalyst loading on
a per Co basis relative to alcohol. c Isolated yields based on alcohol.
d Determined by chiral HPLC or GC analysis.
ring opening provides an attractive strategy for the direct
preparation of optically active monoprotected 1,2-diols. The model
reaction of benzyl alcohol and (()-1,2-epoxyhexane was catalyzed
by 5 with complete regioselectivity to afford 1-benzyloxy-2-
hexanol in highly enantioenriched form, while monomeric
catalysts displayed very low levels of reactivity. A variety of
alcohols and epoxides were found to participate effectively in
the ring opening reaction catalyzed by 5 (Table 1). Thus, 1,2-
diols bearing benzyl, substituted benzyl,14 allyl, and SEM protec-
tion on the primary alcohol were synthesized in high yield and
enantioselectivity, and with complete regioselectivity.
The enhanced reactivity displayed by 5 prompted us to evaluate
its activity in the hydrolytic kinetic resolution (HKR) of terminal
epoxides.1b Using conditions optimized for isolation of either
epoxide or diol, the use of 5 allowed a 10- to 50-fold decrease in
Co concentration, with a simultaneous decrease in reaction time
by a factor of up to 16.15 The results with epichlorohydrin
highlight the practical potential of the new catalyst in the HKR:
under solvent-free conditions, 0.5 mol were resolved in 11 h at
room temperature using only 50 mg of catalyst, providing 23 g
of recovered epoxide in >99% ee.
Acknowledgment. This work was supported by the NIH (GM-43214)
and by a fellowship to J.M.R. from the American Chemical Society. We
thank Dr. J. Karl for important background experiments.
Supporting Information Available: Experimental details of the
catalyst synthesis, the epoxide ring-opening reactions, and the kinetic
studies (PDF). This material is available free of charge via the Internet
at http://pubs.acs.org.
Similar improvements in reactivity relative to monomeric
complexes were observed in the kinetic resolution of terminal
JA005867B
(13) Racemic opening of epoxides with alcohols: Iranpoor, N.; Shekarriz,
M.; Shiriny, F. Synth. Commun. 1998, 28, 347-366.
(16) Initial rates were determined over a 10-fold concentration range of
catalyst ([Co] ) 0.93-9.3 mM). Reactions were performed at 30 °C with
[epoxide]0 ) 2.96 M and [phenol]0 ) 1.33 M.
(17) Ready, J. M.; Jacobsen, E. N. J. Am. Chem. Soc. 1999, 121, 6086-
6087.
(14) For the use of 2-bromobenzyl ethers as protecting groups, see: Plante,
O. J.; Buchwald, S. L.; Seeberger, P. H. J. Am. Chem. Soc. 2000, 122, 7148-
7149.
(15) A table of specific examples is provided as Supporting Information.