Asymmetric alkene epoxidation with chromium oxo salen complexes. Effect of added phosphoryl ligands

Article abstract of DOI:10.1016/S0040-4039(02)00193-4

In the stoichiometric asymmetric epoxidation of E-β-methylstyrene with cationic chromium-salen oxo complexes, enantioselectivity is elevated by the addition of many different types of phosphoryl compounds. Triarylphosphine oxides are the most effective, a

Full text of DOI:10.1016/S0040-4039(02)00193-4

TETRAHEDRON
LETTERS
Pergamon
Tetrahedron Letters 43 (2002) 2107–2110
Asymmetric alkene epoxidation with chromium oxo salen
complexes. Effect of added phosphoryl ligands
Nessan J. Kerrigan, Ivan J. Langan, Cormac T. Dalton, Adrian M. Daly, Claudine Bousquet and
Declan G. Gilheany*
Chemistry Department and Conway Institute of Biomolecular and Biomedical Sciences, University College Dublin, Belfield,
Dublin 4, Ireland
Received 5 December 2001; accepted 24 January 2002
Abstract—In the stoichiometric asymmetric epoxidation of E-b-methylstyrene with cationic chromium–salen oxo complexes,
enantioselectivity is elevated by the addition of many different types of phosphoryl compounds. Triarylphosphine oxides are the
most effective, and, amongst them, tris(3,5-dimethylphenyl)phosphine oxide gave the highest ee to date (93%). There is a ceiling
effect of additive, bulky additives are ineffective, there is no substituent electronic effect within the additive and there is a
saturation of its effect with increasing concentration. © 2002 Elsevier Science Ltd. All rights reserved.
The use of metal complexes of chiral salen ligands in
catalytic asymmetric synthesis has been widespread in
recent years. Especially useful is the manganese–salen
were not fully maintained in the catalytic version of the
4b,c,e
reaction, although the latter gave a higher yield.
We
1
4e
proposed an explanation based on reaction of the
Cr(V)ꢀO with its reduced Cr(III) form to give an
unreactive m-oxo dimer, Cr(IV)–O–Cr(IV) (Fig. 1), the
manganese version of which is considered to be the
catalyzed asymmetric epoxidation of conjugated Z-
alkenes (Fig. 1, M=Mn) studied extensively by
2
3
4
Jacobsen and Katsuki. We have reported on the
complementary chiral chromium salen complexes which
give good selectivity for E-alkenes (Fig. 1, M=Cr) and
have the useful feature that the SalCr(V)ꢀO species is
6,8
resting state of the catalyst in the manganese series.
A notable aspect of our system was the change in
enantiomeric excess (ee) by as much as 30% on addition
5
stable, unlike the SalMn(V)ꢀO species which is a fleet-
6
,7
ing intermediate. Use of the isolated Cr(V)ꢀO species
of certain achiral oxo-type ligands (L), such as phos-
(
stoichiometric reaction) then enables separate study of
4b,c,f
phine oxides and amine N-oxides.
In the case of
the stereoselectivity and catalysis issues. We have
shown that the high ees obtained stoichiometrically
5,9
chromium salen complexes, it was known that such
additives are coordinated by the oxygen atom in the
apical position (L in complex 1, Scheme 1), which
weakens the CrꢀO bond and increases epoxidation rate.
We are not aware of any other studies of additives in
the chromium series. In contrast, additives have a wide
range of reported effects on the chiral manganese–salen
[
O]
M(III)
M(III)
M(V)=O
M(IV)OM(IV)
2,3
epoxidation. We hoped that the stoichiometric vari-
ant of the reaction available in the chromium series
might provide an understanding of the manganese sys-
tem. Our first studies showed that there is a complex
relationship between the effect of L addition and the
salen substituents W–Z in 1. Thus, ee can be increased
O
Figure 1. The catalytic cycle for chromium and manganese
salen epoxidation.
Keywords: asymmetric epoxidation; chromium; salen; phosphine
oxide; meta-effect.
*
Corresponding author. Tel.: +353-1-7162308; fax: +353-1-7162127;
e-mail: declan.gilheany@ucd.ie
Scheme 1.
0
040-4039/02/$ - see front matter © 2002 Elsevier Science Ltd. All rights reserved.
PII: S0040-4039(02)00193-4

2
108
N. J. Kerrigan et al. / Tetrahedron Letters 43 (2002) 2107–2110
The additive triphenylphosphine oxide (TPPO) had pre-
viously been most consistent in raising yield and
4b,c,e,f
ee.
Therefore, we examined a range of substituted
tertiary phosphine oxides with the hope of optimizing
the selectivity and of gaining an understanding of their
mode of action. Table 1 shows results for the
1
0,11
epoxidation
of b-methylstyrene using five of our
12
oxo-chromium(V) salen complexes in combination
with (1 equiv. of) various types of mostly triarylphos-
phine oxides, according to Scheme 1. The presence of
additive usually decreased the reaction time, but only
by as much as half at best, and it usually increased
epoxide yield. However, the best yields were still those
obtained with TPPO, except in the case of complex
13
4f
when substituents are present at X/Z but not at W/Y.
Since then we have embarked on more comprehensive
studies and we now report on phosphorus-containing
additives. Variations in nitrogen-containing and other
additives will be the subject of future reports. The
studies show that a very large range of ligands can
influence the observed selectivities. Included in the
work reported here are a series of triarylphosphine
oxides, one of which provided an improvement to give
our highest ee to date (93%) with our test substrate,
E-b-methylstyrene (Scheme 1).
1
:W=H, X=Z=Br (with the additive at entry 11). All
complexes gave very low yields (<5%) with at least one
additive. Note that the best yields only approach 50%
because the Cr(V)ꢀO species reacts with the Cr(III)
4e
product; the reaction time does not reflect the true
rate of epoxidation for the same reason.
a
Table 1. Results of stoichiometric epoxidation of E-b-methylstyrene according to Scheme 1 with various chiral non-racemic
b
c
substituted oxo-chromium(V) salen complexes in the presence of various substituted triarylphosphine oxides L as added
ligands
Complex
W
X
Y
H
H
H
H
Cl
Cl
H
Br
Br
H
H
Cl
H
H
CF3
Reaction timed
Yield with no additive (%)
Highest yield with additive (%)
ee with no additive
12 h
22
46
60 min
18
40
10 min
60 min
20
90 min
25
2
24
71
35
33
f
g
f
58
67
80/81
88 /90
Entry
Additive L
Increase in ee with additive
e
6/7f
2g/2f
1
2
3
4
5
6
7
8
9
Ph PO
14
14
11
16
6
16
16
16
11
8
3
h
i
i
Ph PO
6
6/6
6 /7
3
h
f
(4-MeOPh) PO
(3-MeOPh) PO
(2-MeOPh) PO
(2,4,6-triMeOPh) PO
(4-FPh) PO
(3-FPh) PO
(pentaFPh) PO
(3,5-diFPh) PO
(3,5-diMePh) PO
(2,4-diMePh) PO
(2,6-diMePh) PO
(2,4,6-triMePh) PO
Oct PO
Bu PO
(EtO) PO
(4-MePhO) PO
6
7
5
−5
−5
3
i
f
3
2
−3
5
3
−2
−23
3
15
13
8
−3
3
11
6
3
14
4
5
1
3
−12
−1
−3
4
−12
−2
3
10
11
12
13
14
15
16
17
18
19
3
7
1
3f
3
3
−7
4
11
5
7
7
3
h
h
h
h
h
h
−2
3
h
1
3
0
3
t
h
3
h
3
h
0
3
j
(C H N) PO
0
0
4
8
3
a
b
c
d
e
f
Procedure (CAUTION) as described in Ref. 10, all at 0°C; ee determined by CSP GC.
A=hexafluorophosphate unless noted otherwise and Y=H in all cases.
1
equivalent added, unless noted otherwise.
Time to discharge of green colour to orange.
Previously reported by us, Ref. 4.
A=nitrate.
g
h
i
Incorrectly reported as 86% (no additive) and 88% (TPPO as additive) in Ref. 4e.
2
equiv. of additive.
The (SS)-chromium complex was also used and gave the same ee of opposite enantiomer of epoxide.
Tris(1-pyrrolidinyl)phosphine oxide.
j

N. J. Kerrigan et al. / Tetrahedron Letters 43 (2002) 2107–2110
2109
A general trend in enantioselectivity is visible in Table
. The five complexes are arranged in order of increas-
tris(amino)phosphine oxide has no effect (entry 19).
17l
1
Phosphoryl chloride destroys selection.
ing ee without additive, and it can be seen very clearly
that the beneficial effect of additive becomes less as the
ee without additive increases. Thus, the values of the
entries become smaller or go negative to the right in
Table 1. This confirms previous observations with our
earlier more limited additive set. We refer to it as a
ceiling effect of additive. It can be explained if changes
in the salen-substitution pattern produce the same
effect as addition of ligand L, but with the latter giving
the weaker effect. Our working hypothesis is that both
Z-substituents and additives L can favorably influence
the conformation of complex 1 to give better selectivity.
In complexes with suitable Z-substituents, the confor-
mation without L reaches an optimum and the effect of
L is thus minimal. However, the same effects could be
produced by variations in the equilibrium involving
complex with and without additive (vide infra).
In all cases examined, addition of a second (or further)
equivalent of TPPO had no extra effect, giving the same
ee elevation as the first equivalent (Table 1, entry 2).
Indeed we found that maximum ee elevation is already
attained at substantially less than one equivalent of
additive. For example, with TPPO and complex 1:
W=X=H, Z=Cl, the maximum elevation (6) is
achieved at 0.2 equivalents. A similar result was
obtained with TPPO and complex 1: W=X=Z=Cl.
On the other hand, for the case of tris(3,5-
dimethylphenyl)phosphine oxide as additive with com-
plex 1: W=H, X=Z=Br, the maximum elevation (8)
was not achieved until approximately 0.5 equivalents of
additive were present.
4
c
It is clear that addition of tertiary phosphine oxide
increases rate and enantioselectivity. The latter, in turn,
could mean that the presence of L changes the confor-
mation of the complex. This would be in accord with
and support similar recent proposals by Wiest, Plattner
Table 1 also shows the effects on enantioselectivity of
substitution within the aryl rings of TPPO. The most
immediately obvious, and disappointing, observation is
that substitution mostly does not lead to increased
selectivity. Thus, of the approximately 50 new data
points in Table 1, only three are higher than obtained
with TPPO. ortho-Substitution leads to lower, some-
times much lower, selectivity (compare: entries 5/6 to
7
and co-workers in the manganese series. However, it
could also be that the presence of L affects the balance
between the epoxidation rates of two different oxidants.
We have previously had to postulate a second oxidant
4e
in the catalytic version of the reaction. Also, there are
other aspects of the results that present a dilemma in
analysis. With rate acceleration at less than one equiva-
lent of L, these effects are examples of ligand-acceler-
3
/4; 12/13/14 to 11; 16 to 1), assumed to be a steric
effect. It is also noticeable that electronic effects are
small, with electron donating groups (EDGs) only mar-
ginally better for selection than electron withdrawing
groups (EWGs) (compare entries 3/7 and 4/8: five
examples, two counter examples). Both EWGs and
EDGs are usually worse than TPPO itself, again this is
less noticeable with the EDGs (one example greater). It
is not clear at this time why EDGs and EWGs should
give similar changes in selectivity.
18
ated catalysis. However, they are lower than expected
5
from the work of Kochi and co-workers, who found
orders of magnitude accelerations with similar L and
achiral SalCr(V)ꢀO. On the other hand, the observed ee
elevations, especially at lower L concentrations, require
a substantially higher rate for LSalCr(V)ꢀO over Sal-
Cr(V)ꢀO. This is because the formation constant for
5
LsalCr(V)ꢀO is not very high. Kochi and co-workers
−
1
More encouraging was the observation that an EDG at
estimated it at approx. 13 M for L=Et PO with
3
the meta-position appears to be mostly beneficial
achiral SalCr(V)ꢀO. They also noted that it decreased
as the bulk of the additive increased. With one equiv. of
L, this corresponds to a ratio of LSalCr(V)ꢀO to Sal-
Cr(V)ꢀO of about 3. In addition, as the product Sal-
(
entries 4/11) and leads to our best ee to date (93%) for
complex 1 (W=X=H, Z=CF ) with L=tris(3,5-
3
dimethylphenyl)phosphine oxide, marginally better
than with TPPO. This additive also provides the best
selectivity with other salen complexes that we have
studied, for example with 1 (W=Cl, X=Z=H, not in
Table 1) it gives an ee of 80%, again marginally better
than with TPPO. This effect appears to be a combina-
tion of electronic and steric factors and has good
precedence in the recent literature of enantioselective
Cr(III) species builds up, it should sequester L as
5
L Cr(III). These considerations lead us to suspect that
2
the role of L in the chromium series is more complex
5
than previously envisaged and we are engaged in fur-
ther experiments to investigate this.
In summary, we have found that, in epoxidations by
SalCr(V)ꢀO complexes, many phosphoryl additives give
ee elevation, subject to a ceiling with the more benefi-
cial salen substituents. The effect falls off with increas-
ingly bulky substituents but there is almost no
electronic effect of the substituents. The elevation satu-
rates at less than one equivalent of additive.
1
4–16
catalysis.
Many other types of phosphoryl compound can lead to
an increase in selectivity (Table 1 and Ref. 17). How-
ever, none are as good as TPPO. Indeed introduction of
any non-aryl group in TPPO reduces the ee eleva-
1
7b
tion. Symmetrical trialkylphosphine oxides (entry 15;
Ref. 17c,d,e) do mostly give some reasonable ee eleva-
tion so long as they are not bulky (entry 16).
Acknowledgements
1
7a
17f
Unsymmetrical
so long as they are not bulky as are phosphinate
and phosphates (entries 17, 18, Ref. 17i,j,k) but
and asymmetric cases are similar
17g 17h
The authors are grateful to Professor O. Wiest for
helpful discussions. C.B. acknowledges a Marie Curie

2
110
N. J. Kerrigan et al. / Tetrahedron Letters 43 (2002) 2107–2110
Fellowship (No ERB4001GTR921129) from the
European Commission. We thank Enterprise Ireland
0°C. The donor ligand (L) (1 equiv.) was added followed
5 min later by the alkene substrate (9–12 ml, 1 equiv.) and
the solution was left until an orange/brown colour per-
sisted. After evaporation and short path chromatography
(
Grants SC/93/213, SC/94/569 and SC/97/536, Scholar-
ships for N.J.K., I.J.L.), University College Dublin for
Demonstratorships (N.J.K., I.J.L., A.M.D.), and Scher-
ing Plough (Avondale) Ltd. for an Irish American
Partnership Scholarship (C.T.D.). We also thank Drs.
Kenneth Ryan, Valerie Wall, Marie Renehan and Colm
O’Mahony for additional experiments.
(alumina, Et O), analysis was by GLC on a Supelco
2
a-cyclodextrin capillary column with n-decane as internal
standard. As discussed previously (Ref. 4e), reduced
yields are partially accounted for by recovered alkene,
along with some benzaldehyde and benzyl methyl ketone.
Burn ratios used and determination of absolute configu-
rations have been given previously (Ref. 4e).
References
1
1. We confirmed that the influence of small amounts of
water and atmospheric oxygen on the reaction was mini-
mal. We have previously shown that the effects of
extended reaction times and possible kinetic resolution
effects are not significant under these conditions (Ref.
1
. Canali, L.; Sherrington, D. C. Chem. Soc. Rev. 1999, 28,
5–93.
8
2
. Jacobsen, E. N.; Wu, M. H. In Comprehensive Asymmet-
ric Catalysis; Jacobsen, E. N.; Pfaltz, A.; Yamamoto, H.,
Eds.; Springer: New York, 1999; Chapter 18.2, pp. 649–
4e). The solvent used was acetonitrile but similar results
were obtained in more limited studies using
dichloromethane: O’Mahony, C. P.; Gilheany, D. G.;
unpublished results.
6
77.
3
4
. Katsuki, T. In Catalytic Asymmetric Synthesis, 2nd ed.;
Ojima, I., Ed.; Wiley-VCH: New York, 2000; Chapter
1
2. We have previously described in detail (Ref. 4e) the
synthesis of the precursor Cr(III) trifluoromethyl com-
plexes. The other precursor Cr(III) complexes used in this
work were synthesized in an analogous manner.
3. Most L are known compounds, prepared in short syn-
thetic sequences, while a few were available commercially.
4. (a) Trabesinger, G.; Albinati, A.; Feiken, N.; Kunz, R.
W.; Pregosin, P. S.; Tschoerner, M. J. Am. Chem. Soc.
6
B, pp. 287–325.
. (a) Dalton, C. T.; Ryan, K. M.; Wall, V. M.; Bousquet,
C.; Gilheany, D. G. Top. Catal. 1998, 5, 75–91; (b)
Bousquet, C.; Gilheany, D. G. Tetrahedron Lett. 1995,
1
1
3
6, 7739–7742; (c) Ryan, K. M.; Bousquet, C.; Gilheany,
D. G. Tetrahedron Lett. 1999, 40, 3613–3616; (d) Daly,
A. M.; Dalton, C. T.; Renehan, M. F.; Gilheany, D. G.
Tetrahedron Lett. 1999, 40, 3617–3620; (e) Daly, A. M.;
Renehan, M. F.; Gilheany, D. G. Org. Lett. 2001, 3,
1997, 119, 6315–6323; (b) Selvakumar, K.; Valentini, M.;
Pregosin, P. S.; Albinati, A.; Eisentrager, F.
Organometallics 2000, 19, 1299–1307 and references cited
therein.
6
63–666; (f) O’Mahony, C. P.; McGarrigle, E. M.; Rene-
han, M. F.; Ryan, K. M.; Kerrigan, N. J.; Bousquet, C.;
Gilheany, D. G. Org. Lett. 2001, 3, 3435–3438.
. Samsel, E. G.; Srinivasan, K.; Kochi, J. K. J. Am. Chem.
Soc. 1985, 107, 7606–7617.
. Srinivasan, K.; Michaud, P.; Kochi, J. K. J. Am. Chem.
Soc. 1986, 108, 2309–2320.
. (a) Feichtinger, D.; Plattner, D. A. Angew. Chem., Int.
Ed. Engl. 1997, 36, 1718–1719; (b) Plattner, D. A.;
Feichtinger, D.; El-Bahraoui, J.; Wiest, O. Int. J. Mass
Spectrom. 2000, 195/196, 351–362; (c) Feichtinger, D.;
Plattner, D. A. J. Chem. Soc., Perkin Trans. 2 2000,
1
5. RajanBabu, T. V.; Radetich, B.; You, K. K.; Ayers, T.
A.; Casalnuovo, A. L.; Calabrese, J. C. J. Org. Chem.
5
6
7
1999, 64, 3429–3447 and references cited therein.
1
6. (a) Hayashi, T.; Hirate, S.; Kitayama, K.; Tsuji, H.;
Torii, A.; Uozumi, Y. J. Org. Chem. 2001, 66, 1441–1449;
(
b) Hayashi, T.; Hirate, S.; Kitayama, K.; Tsuji, H.;
Torii, A.; Uozumi, Y. Chem. Lett. 2000, 1272–1273; (c)
Senda, T.; Ogasawara, M.; Hayashi, T. J. Org. Chem.
2001, 66, 6852–6856; (d) Blaser, H. U.; Buser, H. P.;
Hausel, R.; Jalett, H. P.; Spindler, F. J. Organomet.
Chem. 2001, 621, 34–38; (e) Vedejs, E.; Daugulis, O.;
MacKay, J. A.; Rozners, E. Synlett 2001, 1499–1505 and
references cited in this account.
1
023–1028; (d) Feichtinger, D.; Plattner, D. A. Chem.
Eur. J. 2001, 7, 591–599; (e) El-Bahraoui, J.; Wiest, O.;
Feichtinger, D.; Plattner, D. A. Angew. Chem., Int. Ed.
2
001, 40, 2073–2076.
1
7. Other ee results for 1: L, W,X,Z, ee increase %: (a)
8. Bryliakov, K. P.; Babushkin, D. E.; Talsi, E. P. J. Mol.
1
-NapPh PO, H,H,Cl, 3; (b) Ph MePO, H,H,Cl, −1; (c)
Catal. A: Chem. 2000, 158, 19–35.
2 2
n
Et PO, H,H,Cl: 11; (d) Bu PO: Cl,Cl,Cl, 4; (e) Oct PO,
9. Sidall, T. L.; Miyaura, N.; Huffmann, J. C.; Kochi, J. K.
J. Chem. Soc., Chem. Commun. 1983, 1185.
3
3
3
Cl,Cl,Cl, −1; (f) (±)-oAnMePhPO, H,H,H, 11; H,H,Cl, 6;
g) (±)-1-NapMePhPO, H,H,Cl, −2; (h) (±)-
(
1
0. Experimental procedure. CAUTION: Cr(V)ꢀO species
are known carcinogens, all complexes were generated in
situ. To the appropriate precursor (salen)Cr(III) complex
n
MeOMePhPO, H,H,H, 8; (i) ( HexO) PO, H,HH, 12;
3
H,H,Cl, −4; (j) (Me CH(CH ) O) PO, H,H,H, 7; H,H,Cl,
3
2 4
3
3
; Cl,Cl,Cl, 7; (k) (EtO) PO, Cl,Cl,Cl, 7; (l) Cl PO,
(
30–50 mg, 1 equiv.) in CH CN (5 mL) was added
3
3
3
Cl,C,Cl, −32.
iodosylbenzene (1–2 equiv.). A deep green/black colour
appeared almost immediately. After stirring for 30 min
this solution was filtered and the filtrate was cooled to
18. Berrisford, D. J.; Bolm, C.; Sharpless, K. B. Angew.
Chem., Int. Ed. Engl. 1995, 34, 1059–1070.