Stereoselective epoxidation of electron poor dienes using poly(L-leucine)

Article abstract of DOI:10.1039/a706238i

Poly(L-leucine) catalysed oxidation of dienes 2, 3, 10, 16 and 18 and the triene 17 furnishes the corresponding epoxides 4, 5, 11, 19, 21 and 20 respectively in good to excellent yield and in states of high optical purity. Some regioselective reactions of the saturated epoxy ketones 5 and 11 are described.

Full text of DOI:10.1039/a706238i

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Stereoselective epoxidation of electron poor dienes using
poly(L-leucine)
Joanne V. Allen, Michael W. Cappi, Pierre D. Kary, Stanley M. Roberts,
Natalie M. Williamson and L. Eduardo Wu
Department of Chemistry, University of Liverpool, Liverpool, UK L69 7ZD
Poly(L-leucine) catalysed oxidation of dienes 2, 3, 10, 16
and 18 and the triene 17 furnishes the corresponding
epoxides 4, 5, 11, 19, 21 and 20 respectively in good to excel-
lent yield and in states of high optical purity. Some regio-
selective reactions of the saturated epoxy ketones 5 and 11
are described.
5 h using urea hydrogen peroxide (UHP) and 1,8-diazabicyclo-
[5.4.0]undec-7-ene (DBU) in tetrahydrofuran under catalysis by
poly(-leucine) to give the epoxides 4 (95% yield, 90% ee) and 5
(90% yield, 90% ee) respectively. Use of poly(-leucine) in the
preparation of ent-5 gives comparable results (91% yield, 95%
ee).
The optically active products are susceptible to attack at
multiple points by other reagents; the ketone carbonyl group,
the alkene moiety and the ester unit may be attacked in a
chemoselective fashion. For example, reaction of the keto ester
5 with methylmagnesium chloride gives the tertiary alcohol 6 as
the only stereoisomer (70% yield) (Scheme 2).
The stereoselective oxidation of chalcones using basic hydrogen
peroxide and poly(L-leucine) was pioneered by Banfi et al.1 We
have shown that the original three-phase oxidation system
could be applied to α,β-unsaturated ketones other than chal-
cones (1,3-diphenylprop-2-en-1-ones).2 Use of a two-phase
oxidation method considerably enhanced the rate of oxidation
of chalcones and allowed the range of substrates to be extended
further.3
H3CO
O
O
α,β-Unsaturated esters as well as vinyl chlorides and electron
rich alkenes are totally unreactive even under the new con-
Ph
OH
H3CO
O
O
O
O
OH
9
ditions. Less predictably α-methylchalcone [PhCH᎐C(CH )-
᎐
3
COPh] is far less reactive than chalcone itself; the relative rates
of oxidation of α,β-unsaturated carbonyl compounds can be
ordered qualitatively as shown below.
Ph
OH
OH
iii
iv
8
O
OCH3
Ph
Ph
CH3
Ph
O
~
O
>
>>
~
,
5
ii
O
O
O
O
O
CH3
i
OCH3
OCH3
,
Ph
OH
O
O
HO
Ph
CH3
OCH3
7
O
Cl
O
6
While the lack of reactivity of species such as cinnamate
esters is disappointing, the marked difference in reactivity of
different alkenes may be used to advantage in some circum-
stances.
Scheme 2 Reagents and conditions: i, MeMgCl, THF, 71%; ii,
MeLiCuCN, THF, 30%; iii, ‘super’ AD mix α, 58%; iv, ‘super’ AD mix
β, 68%
For example keto esters 2 and 3 are readily prepared from the
aldehyde 1 (Scheme 1) and are readily oxidised over a period of
In contrast, reaction of compound 5 with LiCuCNMe gave
the epoxy-ring opened product 7 albeit in modest yield.
Dihydroxylation of the alkene unit in compound 5 with N-
methylmorpholine N-oxide and a catalytic amount of osmium
tetraoxide gave an inseparable mixture of the diols 8 and 9 in
the ratio 2:1. Good control over the introduction of the cis-diol
unit is achieved using the ‘super’ AD mix preparations recom-
mended by Sharpless et al.4 (Scheme 2).
O
O
i
H
OR
Ph
Ph
O
O
2 R = But
3 R = CH3
1
The asymmetric epoxidation of the dienone 10 (naphthyl
refers to the 2-naphthyl isomer) gives the oxirane 11 with
poly(-leucine) and the enantiomer ent-11 with poly(-leucine)
(Scheme 3).5 Once again the differing reactivity of the alkene
unit, the epoxide moiety and the carbonyl group may be used to
advantage. Thus, bis-hydroxylation and acetonide formation,
according to Sharpless’s rules,4,6 allows access to the compound
12; reaction of this compound with higher order cuprate leads
to opening of the three-membered ring and formation of the
secondary alcohol 13. The latter product was unexpected and
ii
O
OR
Ph
O
O
4 R = But
5 R = CH3
Scheme 1 Reagents and conditions: i, Ph3P᎐CHCO2R, PhCH3, 70%;
ii, poly(L-leucine), urea hydrogen peroxide, DBU, THF, 90%
᎐
J. Chem. Soc., Perkin Trans. 1, 1997
3297

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O
O
O
O
ii
H3C
Naphthyl
Naphthyl
Ph
Naphthyl
Ph
Ph
Cl
Ph
O
ent–11
O
10
17
16
i
CH3
O
Ph
O
O
Ph
Ph
iii
O
Ph
Naphthyl
18
O
O
O
O
11
12
O
O
O
O
iv
H3C
Cl
Ph
Ph
O
O
Ph
OH
20
19
Naphthyl
O
CH3
O
O
O
Ph
Ph
13
O
Scheme 3 Reagents and conditions: i, poly(-leucine), urea hydrogen
peroxide, DBU, THF, 85%, 96% ee; ii, poly(D-leucine), urea hydrogen
peroxide, DBU, THF, 80%, 90% ee; iii, (a) AD mix-β, 95%, (b) for
clarity (D-2,2Ј-dimethoxypropane, toluene-p-sulfonic acid (p-TSA,
cat.), acetone, 92%; iv, MeLiCuCN, THF, 55%
21
Experimental
Procedure for the poly(L-leucine) oxidation of dienone ester 3
To a solution of the dienone 3 (3.96 mmol) in THF (13 cm3) was
added successively poly(-leucine) (1.65 g), urea–hydrogen per-
oxide (447 mg, 4.8 mmol, 1.2 equiv.), and DBU (718 µl, 4.8
mmol, 1.2 equiv.). The reaction mixture was stirred at room
temperature for 5 h after which time TLC analysis (50% ethyl
acetate–light petroleum) indicated total consumption of start-
ing material. The poly(-leucine) was removed by suction fil-
tration, washing with ethyl acetate. The filtrate was concen-
trated in vacuo and the resulting brown residue was purified by
flash-column chromatography [light petroleum–ethyl acetate
(70:30)] to yield the epoxide 5 as a colourless solid (90%), mp
58–59 ЊC; [α]D23 Ϫ80.4 (c 1.15, CHCl3) (Found: Mϩ, 232.07331.
C13H12O4 requires M, 232.07356); δH(300 MHz; CDCl3) 3.71
was characterised only after a full spectroscopic data set had
been obtained.†
Subsequent oxidation of 13 under standard Baeyer–Villiger
conditions gave the ester 14, which was then treated with
O
OH
Ph
O
OH
Ph
mCPBA
pH 7 buffer
Naphthyl
NaphthylO
O
O
CH2Cl2
54%
O
O
13
14
CF3CO2H
H2O
57%
Ph
(1H, dd, J 1.8 and 7.2, ᎐CHCHO), 3.78 (3H, s, OCH ), 4.24
᎐
3
O
O
HO
(1H, d, J 1.8, CHOC᎐O), 6.28 (1H, d, J 15.7, ᎐CHCO CH ),
᎐
᎐
2
3
6.78 (1H, dd, J 7.2 and 15.7, ᎐CHCHO), 7.49–7.54 (2H, m,
2 × ArCH), 7.62–7.67 (1H, m, ArCH), 8.01 (2H, d, J 7.0,
2 × ArCH); δC(75 MHz; CDCl3) 51.90 (OCH3), 56.94 (CHO),
᎐
HO
15
58.67 (CHO), 125.64 (᎐CH), 128.44 (᎐CH), 129.02 (᎐CH),
᎐
᎐
᎐
aqueous trifluoroacetic acid to afford the γ-lactone 15 in 57%
yield over two steps.‡
134.26 (᎐CH), 135.35 (ArC), 142.20 (᎐CH), 165.69 (C᎐O),
᎐
᎐
᎐
192.63 (C᎐O); νmax(thin film)/cmϪ1 1722 (ester C᎐O), 1689
᎐
᎐
Finally, the chlorodiene 16, the trienone 17 and alkylated
dienone 18 were oxidised with urea–hydrogen peroxide under
catalysis by poly(-leucine) to furnish the epoxides 19 (57%
yield, 86% ee), 20 (43% yield, 90% ee) and 21 (70% yield, 92%
ee) with remarkable selectivity, emphasising the predictability
and regioselectivity of the oxidation process on the basis of
double bond reactivity as shown above.
(ketone C᎐O), 1231 (epoxide); m/z (EI) 232 (Mϩ, 1%), 217
᎐
(Mϩ Ϫ CH3, 3), 201 (217 Ϫ O, 2), 105 (PhCO, 100).
Acknowledgements
We thank the BBSRC for a postgraduate assistantship (P. D. K.)
and postdoctoral fellowships (to J. V. A. and N. M. W.). The
Leverhulme Centre for Innovative Catalysis provided a student-
ship (L. E. W.).
† [α]D29 ϩ50 (c 0.8, CHCl3) (Found: MHϩ, 377.174 81. C24H24O4 requires
MH, 377.175 29); δH(400 MHz; CDCl3) 1.59 (3H, s, CH3), 1.62 (3H, s,
CH3), 3.18 (1H, dd, J 3.1 and 17.4, CHHЈ), 3.21 (1H, s, OH, exchange-
able with D2O), 3.48 (1H, dd, J 9.0 and 17.4, CHHЈ), 3.88 (1H, dd, J 8.6
and 1.8, CHO), 4.36 (1H, approx. dt, J 9.0 and 2.5, CHOH), 5.17 (1H,
d, J 8.6, CHO), 7.48 (7H, m, 6 × naphthyl-CH, 1 × Ar-CH), 7.91 (4H,
m, ArCH), 8.40 (1H, s, naphthyl-CH); δC(75 MHz; CDCl3) 26.92
(CH3), 27.32 (CH3), 43.01 (CH2), 65.21 (CHOH), 78.78 (CHO), 85.55
(CHO), 109.52 [(CH3)2C], 123.67 (naphthyl-CH), 126.93, 127.87,
128.46 (Ph-CH), 128.59, 128.77, 129.68, 130.13 (naphthyl-CH), 132.53,
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᎐
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Paper 7/06238I
Received 26th August 1997
Accepted 10th September 1997
(ArCH), 128.22 (ArCH), 140.50 (ArC), 175.65 (C᎐O); m/z (CI) 226
᎐
(M ϩ NH4, 100%), 208 (M ϩ NH4 Ϫ H2O, 44%).
3298
J. Chem. Soc., Perkin Trans. 1, 1997