Asymmetric epoxidation of some arylalkenyl sulfones using a modified Juliá-Colonna procedure

Article abstract of DOI:10.1016/j.tetlet.2004.04.190

A modified procedure for performing the Juliá-Colonna epoxidation reaction effects the oxidation of some vinyl sulfones to generate the corresponding epoxides 5-8 in good to excellent optical purity.

Full text of DOI:10.1016/j.tetlet.2004.04.190

Tetrahedron
Letters
Tetrahedron Letters 45 (2004) 5073–5075
Asymmetric epoxidation of some arylalkenyl sulfones using a
ꢀ
modified Julia–Colonna procedure
Jose-Maria Lopez-Pedrosa,a Michael R. Pitts,a Stanley M. Roberts,a,b,
Shanthini Saminathanb and John Whittalla
*
aStylaCats Ltd., University of Liverpool, Liverpool L69 7ZD, UK
bDepartment of Chemistry, Robert Robinson Laboratories, University of Liverpool, Liverpool L69 7ZD, UK
Received 23 February 2004; revised 21 April 2004; accepted 30 April 2004
ꢀ
Abstract—A modified procedure for performing the Julia–Colonna epoxidation reaction effects the oxidation of some vinyl sulfones
to generate the corresponding epoxides 5–8 in good to excellent optical purity.
ꢀ 2004 Elsevier Ltd. All rights reserved.
1. Introduction and background information
reaction times (from ca. 16 to 1 h for chalcone oxida-
tion);
The employment of amino acids and low molecular
weight peptides as catalysts in asymmetric syntheses is a
subject of considerable current interest.1 One of the first
transformations to be investigated was the asymmetric
epoxidation of a,b-unsaturated ketones using aqueous
sodium hydroxide with 30% hydrogen peroxide and a
• production of immobilised catalyst7 (aiding recovery
and recycling) and homogeneous catalyst8 (for use
in membrane reactors9);
• substantial expansion of the range of a,b-unsaturated
ketones undergoing epoxidation, giving ready access
to a wide range of intermediates useful for the pro-
duction of an impressive portfolio of natural prod-
ucts10 and biologically active compounds.11
polyamino acid as the catalyst, a transformation dis-
2
covered by Julia and Colonna. The first documented
ꢀ
reaction mixture consisted of three phases, namely the
aqueous phase, an organic solvent such as hexane or
toluene and the insoluble polyamino acid such as poly-
alanine or polyleucine.
Recent work in the Bayer (Leverkeusen) laboratories
has resulted in yet another significant improvement in
ꢀ
the operation of the Julia–Colonna reaction. Thus
Geller et al.12 have shown that modification of the ori-
ginal triphasic conditions through inclusion of a phase
transfer catalyst (PTC) in the mixture gave rise to a
much faster reaction. Most significantly, the amount of
catalyst required was greatly reduced, 0.5 mol % of poly-
(L)-leucine being required for oxidation of chalcone
over 1.5 h.
The reaction has been developed and improved in recent
years in a variety of ways; some of the noteworthy
developments are as follows:
• production of the catalyst on a large scale3 and the
commercial availability of the polyamino acids;4
• modification of the protocol to allow the use of other
oxidants, such as percarbonate5 and urea hydrogen
peroxide (UHP),6 under nonaqueous two-phase con-
ditions with consequent reduction in the amount of
catalyst required (from ca. 20 to 5 mol %) and also
Contemporaneous work in the Liverpool laboratories
had shown that, in the two-phase system, mixing UHP
and poly-(L)-leucine in an organic solvent resulted in
rapid transfer of peroxide into the polyamino acid gel.13
This observation led us to speculate and then investigate
whether a polyamino acid could abstract hydrogen
peroxide from aqueous solution as used in the cheaper
three-phase system and, if so, whether the resulting
* Corresponding author. E-mail: smrsm@liv.ac.uk
0040-4039/$ - see front matter ꢀ 2004 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetlet.2004.04.190

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J.-M. Lopez-Pedrosa et al. / Tetrahedron Letters 45 (2004) 5073–5075
ꢀ
Table 1. Epoxides produced from the modified Julia–Colonna procedure
Entry
Epoxide formed
Literature reference
Reaction time (h)
Conversion % (isolated yield)
Optical purity of epoxide ee (%)
1
2
3
4
5
6
7
8
1
2
3
4
5
6
7
8
1
14
15
6
6
3
100 (80)
66 (51)
56 (51)
80 (60)
–– (66)
65 (49)
–– (61)
89 (76)
95
>95
>95
>95
91
3
3
16
––
––
––
6
6
94
95
6
18
70
ꢀ
material could be utilised to perform Julia–Colonna
oxidations.
In summary, this communication highlights the fact
that, surprisingly, polyleucine sequesters peroxide from
aqueous solution. The resultant polyamino acid/perox-
ide-containing gel efficiently oxidizes a selection of, a,b-
unsaturated ketones and, notably, transforms a small
range of arylvinyl sulfones to furnish the corresponding
optically active epoxides having good to excellent opti-
2. Results and discussion
Poly-(L)-leucine (insoluble, 0.1 mol %) was stirred with
aqueous sodium hydroxide (5 M, 2.0 equiv), hydrogen
peroxide (30%, 1.8 equiv), tetra-butylammonium
hydrogensulfate (1.5 mol %) and toluene. After 3 h, the
aqueous phase was removed to leave a biphasic system
(toluene and gel-like polyamino acid containing perox-
ide) to which chalcone was added. After 6 h, the epoxi-
dation reaction was complete and (2R,3S)-chalcone
epoxide 1 (Table 1, entry 1) was isolated in 95% ee. The
reaction has been conducted on a 5 g scale.
ꢀ
cal purity. Thus this latest modification of the Julia–
Colonna oxidation system represents the simplest,
cheapest and fastest way to effect the asymmetric
epoxidation of a wide range of substrates, including
unsaturated ketoesters and vinyl sulfones.
Acknowledgements
The reaction was applied to benzylidene acetone (entry
2) to afford the bis-epoxide 2 and the meso-isomer (de
92%). Of greater interest was that the hydroxide-sensi-
tive esters ethyl 3-oxo-3-phenylbut-2-enoate14 and
methyl 6-oxo-6-phenylhex-2,4-dienoate15 afforded the
epoxides 3 and 4 (Table 1, entries 3 and 4) in high yields
and excellent enantiomeric excesses. Such esters were
found to give baseline materials under the oxidation
conditions recommended by the Bayer scientists.
The Royal Society is thanked for provision of a Devel-
oping World Study Visit (to S.S.).
References and notes
1. Jarvo, E. R.; Miller, S. J. Tetrahedron 2002, 58, 2481–
2499.
ꢀ
2. Banfi, S.; Colonna, S.; Molinari, H.; Julia, S.; Guixer, J.
Tetrahedron 1984, 49, 5207–5211.
Attempts have been made previously to oxidize phenyl
ꢀ
styrylsulfone under Julia–Colonna conditions, with very
limited success.16 Gratifyingly, slight modification of the
new conditions17 provided a protocol better suited to the
oxidation of vinyl sulfones as illustrated by the last four
entries in Table 1. Thus phenylstyryl sulfone was oxi-
dized in standard fashion to afford the crystalline
epoxide 5, in 91% ee.18 The corresponding para-
bromostyryl sulfone and phenyl(3-pyridyl) vinyl sulfone
gave the epoxides 6 and 7 in similar optical purities.
Perhaps of greatest significance, para-tolyl vinyl sulfone
was oxidised relatively slowly, but cleanly to afford the
novel epoxide 8. The optical purity of the product is
moderate (70% ee) but the transformation has not been
optimised.
3. Baars, S.; Drauz, K.-H.; Krimmer, H.-P.; Roberts, S. M.;
Sander, J.; Skidmore, J.; Zanardi, G. Org. Process Res.
Dev. 2003, 7, 509–517.
4. Polyamino acid catalysts are available from Lancaster
Synthesis Ltd.
5. Allen, J. V.; Drauz, K.-H.; Flood, R. W.; Roberts, S. M.;
Skidmore, J. Tetrahedron Lett. 1999, 40, 5417–5420.
6. Allen, J. V.; Bergeron, S.; Griffiths, M. J.; Mukherjee, S.;
Roberts, S. M.; Williamson, N. M.; Wu, L. E. J. Chem.
Soc., Perkin Trans. 1 1998, 3171–3179.
7. Geller, T. P.; Roberts, S. M. J. Chem. Soc., Perkin Trans.
1 1999, 1397–1398.
8. Flood, R. W.; Geller, T. P.; Petty, S. A.; Roberts, S. M.;
Skidmore, J.; Volk, M. Org. Lett. 2001, 3, 683–685.
O
O
O
O
O
O
O
O
O
OEt
OMe
Ph
Ph
Ph
Ph
Ph
Ph
Ph
Ph
Ph
O
O
1
2
3
4
O
S
O
O
S
O
O
S
O
S
O
O
O
O
Ph
O
O
Br
N
Me
5
6
7
8

J.-M. Lopez-Pedrosa et al. / Tetrahedron Letters 45 (2004) 5073–5075
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Kuhnle, A.; Krimmer, H.-P.; Drauz, K. Synlett 2002, 707–
15. The tert-butyl ester is epoxidized successfully under the
triphasic conditions Kroutil, W.; Lasterra-Sanchez, M. E.;
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M. Chem. Commun. 1998, 1, 1159–1160; Chen, W.-P.;
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Flowerdew, B. E.; Jackson, M. P.; McCague, R.; Nugent,
T. C.; Roberts, S. M. J. Chem. Soc., Perkin Trans. 1 1997,
3501–3507; Carde, L.; Davies, H.; Geller, T. P.; Roberts,
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12. Geller, T.; Gerlach, A.; Krueger, C. M.; Militzer, H.-C.
Chimica Oggi 2003, 21, 6; Geller, T.; Krueger, C. M.;
Militzer, H.-C., preceding paper.
13. Caroff, E.; Flood, R. W.; Heal, W.; Kelly, D. R.; Roberts,
S. M. Chem. Commun., in press.
16. Bentley, P. A.; Bickley, J. F.; Roberts, S. M.; Steiner, A.
Tetrahedron Lett. 2001, 42, 3741–3743.
17. Typical procedure for sulfone oxidations: Poly-(L)-leucine
(insoluble, 1.0 mol %), Bu4NHSO4 (30 mol %), toluene
(2 mL), NaOH (5 M, 10 equiv) and aq H2O2 (30%, 10 equiv)
were stirred for 3 h. The aqueous layer was removed and
NaOH (5 M, 10 equiv) and H2O2 (30%, 10 equiv) were
added and the mixture was stirred overnight. The aqueous
layer was removed, the substrate (100 mg) added and the
mixture stirred in the dark at room temperature. The
reaction mixture was diluted with ethyl acetate (10 mL) and
the poly-(L)-leucine was removed by filtration, washing
with ethyl acetate. The filtrate was washed with water
(3 · 10 mL), dried (MgSO4) and concentrated in vacuo to
give the product. Purification by flash chromatography
(ethyl acetate:hexane) yielded the epoxide.
14. Lasterra-Sanchez, M. E.; Roberts, S. M. J. Chem. Soc.,
Perkin Trans. 1 1995, 1467–1468; See also Porter, M. J.;
Roberts, S. M.; Skidmore, J. Bioorg. Med. Chem. 1999, 7,
2145–2156.
18. The absolute configurations of the epoxysulfones are
tentative, having been assigned on the basis of the
equivalent epoxidation reactions on unsaturated ketones.