Table 3 Asymmetric epoxidation of aliphatic enones 1 using di-tert-butyl tartrate as ligand
Enone
R1
R2
Time/h
Epoxide
Conversiona (yield, %) Ee (%)a
1a
1b
1c
1d
1e
C4H9
C5H11
C6H13
CH3
CH3
CH3
CH3
Et
24
24
24
24
24
2a
2b
2c
ent-2d
2e
92% (53)
96% (59)
92% (63)
95% (67)
Nd (62)
91
93
92
71b
81
3,5-Di-Br-C6H3
CH3
a Conversions and ee values were measured using chiral phase HPLC or GC. Conditions are provided in the supplementary material. Isolated yields refer
to homogeneous material purified by flash chromatography.b
-(2)-di-tert-butyl tartrate was used.
L
hydroperoxide in the presence of 4 Å molecular sieves. The only
drawback was that the conversion to epoxide, whilst initially
fast, rapidly slowed down, presumably as a result of catalyst
inactivation. However, good conversions could be achieved by
portionwise addition of further solid catalyst 3 (total of 25
mol%), which was a straightforward solution to the problem.
Addition of 25 mol% catalyst initially resulted in very poor
conversion. Although in our early experiments we added the
catalyst 3 over a period of 3–5 d, it subsequently became clear
that the additional catalyst could be added much more quickly,
and good conversions could be achieved by addition of a total of
25 mol% catalyst over a period of 24 h. Our results are
summarised in Table 1.
While these results were encouraging, the enantiomeric
excesses that we obtained were lower than those obtained by
Shibasaki. Although in our initial screening of ligands for the
epoxidation of chalcone derivatives we had identified diethyl
tartrate as the optimum choice, the most profitable approach to
the optimisation of our catalyst now appeared to be a re-
appraisal of other related ligands under the new optimised
conditions for epoxidation of aliphatic enones. We therefore
screened a series of tartrate esters, in which the catalyst was
simply prepared in situ.
Scheme 2 Asymmetric epoxidation of aliphatic enones using in situ
generated catalyst.
although the amount of catalyst required is higher (typically 10
mol% for the Mg system, compared with 1–5 mol.% for the La–
BINOL system), the cost of the catalyst precursors is several
orders of magnitude less.
We thank EPSRC for the award of a research grant (GR/
M13633), Rhodia Chirex for studentship support (SJR), and
Professor A. McKillop and Dr S. Bone (formerly Rhodia
Chirex) for helpful discussions.
Thus, tert-butyl hydroperoxide was dried over 4 Å molecular
sieves, Bu2Mg was then added, followed by addition of the
ligand and finally non-3-en-2-one. These conditions were very
closely related to our original conditions for the epoxidation of
chalcone derivatives, with the use of 4 Å molecular sieves as the
only significant alteration to this earlier procedure. Our results
are reported in Table 2, and two striking features are evident.
Firstly the use of tartrate esters derived from secondary or
tertiary alcohols gave much higher conversions with only 10
mol% catalyst, and secondly the observed ee’s were now over
90%.
Notes and references
‡ General procedure for the asymmetric epoxidation of aliphatic
enones using di-tert-butyl tartrate: tert-butyl hydroperoxide (3.7 M in
toluene, 1.1 mmol, 1.1 eq.) was dried over activated powdered 4 Å
molecular sieves (200 mg, activated for 4 h at 200 °C) for 2 h. Bu2Mg (1 M
in heptane, 0.1 mmol, 0.1 eq.) was added. After stirring for 30 min, L-(+)-di-
tert-butyl tartrate (0.11 mmol, 0.11 equiv.) was added. After an additional
period of 30 min stirring, the aliphatic enone (1 mmol) was added, and the
mixture was stirred for 24 h. The conversion and enantiomeric excess were
checked either by chiral phase GC or HPLC. We have observed that best
results are obtained with solutions of tert-butyl hydroperoxide that have
been stored over 4 Å molecular sieves for an extended period.
From these results, the optimum ligand appears to be
commercially available di-tert-butyl tartrate, but the more easily
prepared and cheaper dicycloalkyl tartrates all give good
1 M. J. Porter and J. Skidmore, Chem. Commun., 2000, 1215.
2 D. Enders, J. Zhu and G. Raabe, Angew. Chem., Int. Ed. Engl., 1996, 35,
1725; D. Enders, J. Q. Zhu and L. Kramps, Liebigs Ann.-Recl., 1997,
1101.
3 B. Lygo and P. G. Wainwright, Tetrahedron, 1999, 55, 6289.
4 E. J. Corey and F.-Y. Zhang, Org. Lett., 1999, 1, 1287.
5 R. W. Flood, T. P. Geller, S. A. Petty, S. M. Roberts, J. Skidmore and
M. Volk, Org. Lett., 2001, 3, 683, and references therein.
6 Z.-X. Wang, S. M. Miller, O. P. Anderson and Y. Shi, J. Org. Chem.,
1999, 64, 6443.
7 M. Bougauchi, S. Watanabe, T. Arai, H. Sasai and M. Shibasaki, J. Am.
Chem. Soc., 1997, 119, 2329.
8 T. Nemoto, T. Ohshima, K. Yamaguchi and M. Shibasaki, J. Am. Chem.
Soc., 2001, 123, 2725.
results. Use of -(+)-di-tert-butyl tartrate for the epoxidation of
L
a range of other aliphatic enones resulted in equally good results
for the long chain aliphatic enones, Scheme 2, although the
challenging substrate 1d still falls short of a usable level of
enantiomeric excess. Our results are reported in Table 3.
The higher enantiomeric excesses obtained using the bulkier
ester derivatives may be rationalised on simple steric grounds,
but the apparently higher catalytic activity of the corresponding
magnesium tartrate derivatives of these bulkier tartrate esters is
not so immediately explained. The most probable explanation is
that the magnesium catalysts formed from the bulkier tartrate
esters are simply less prone to hydrolysis, and hence to
inactivation.
9 C. L. Elston, R. F. W. Jackson, S. J. F. MacDonald and P. J. Murray,
Angew. Chem., Int. Ed. Engl., 1997, 36, 410.
10 M. G. Finn and K. B. Sharpless, J. Am. Chem. Soc., 1991, 113, 113.
The magnesium tartrate system appears to offer the prospect
of an alternative to the excellent La–BINOL system in which
Chem. Commun., 2001, 2712–2713
2713
Jacques
