Asymmetric synthesis of trans-disubstituted aryl-vinyl epoxides: A p-methoxy effect

Article abstract of DOI:10.1016/S0040-4039(00)01222-3

It was found that trans-aryl-vinyl epoxides could be synthesized with 77-100% conversion from conjugated aldehydes (which could also behave as Michael acceptors and lead to cyclopropanes) and chiral sulfonium salts with ee's ranging from 95 to 100%. When a p-methoxy group was present on the arylsulfonium salt, the epoxide was the sole product whatever the solvent. (C) 2000 Elsevier Science Ltd.

Full text of DOI:10.1016/S0040-4039(00)01222-3

Tetrahedron Letters 41 (2000) 7309±7312
Asymmetric synthesis of trans-disubstituted aryl-vinyl
epoxides: a p-methoxy e€ect
A. Solladie-Cavallo,* L. Bouerat and M. Roje
   Â
Laboratoire de stereochimie organometallique associe au CNRS, ECPM/Universite L. Pasteur, 25 rue Becquerel,
67087 Strasbourg, France
Â
Received 23 June 2000; accepted 18 July 2000
Abstract
It was found that trans-aryl-vinyl epoxides could be synthesized with 77±100% conversion from
conjugated aldehydes (which could also behave as Michael acceptors and lead to cyclopropanes) and chiral
sulfonium salts with ee's ranging from 95 to 100%. When a p-methoxy group was present on the
arylsulfonium salt, the epoxide was the sole product whatever the solvent. # 2000 Elsevier Science Ltd. All
rights reserved.
Keywords: asymmetric reactions; epoxides; sulfonium salts; phosphazenes.
Disubstituted aryl-vinyl epoxides are important synthetic intermediates and attractive
precursors of functionalized four-carbon sequences. As an application of our asymmetric
synthesis of diaryl epoxides, which have been shown to give almost total enantioselectivities,1 we
present here the enantioselective synthesis of aryl-vinyl epoxides 1a,b to 3a,b (Scheme 1).
Although the aldehydes 7±9 are Michael acceptors and could, in principle, provide cyclopropanes
as already observed,2 asymmetric synthesis of the epoxides 1±3 has been successfully carried out
from ylides 6a and 6b following our method (Scheme 1). The results are gathered in Table 1.
The sulfonium salt 5a was prepared from (R,R,R)-(+)-oxathiane 4 using Vedejs' tri¯ate
method3 (68% isolated yield) and the sulfonium salt 5b was synthesized from p-methoxy-
4
benzyliodide and (R,R,R)-(+)-oxathiane 4 in the presence of AgOTf (1 equiv.) in CH2Cl2 (57%
isolated yield). In both cases, only one diastereomer was formed, as seen from 400 MHz 1H NMR
spectra of the crude products of the reactions, and the (R,R,R,SS)-con®guration was assigned to
the single diastereomer of 5b5 from 1H NMR experiments and by comparison with 5a.6
In a typical experiment, 1 equiv. of the commercially available phosphazene base EtP2 was
added, at ^78ꢀC, to a stirred solution of the benzylic sulfonium salt (5a or 5b: 1 equiv., 1.5 mmol)
in anhydrous CH2Cl2. After stirring for 10±15 min, the aldehyde (1 equiv.) was added dropwise.
* Corresponding author. Tel: +33-3-88136979; fax: +33-3-88136913; e-mail: ascava@ecpm.u-strasbg.fr
0040-4039/00/$ - see front matter # 2000 Elsevier Science Ltd. All rights reserved.
PII: S0040-4039(00)01222-3

7310
Scheme 1.
Table 1
Epoxides 1a,b, 2a,b and 3a,b from addition (at ^78ꢀC) of aldehydes 7±9 on ylides 6a and 6b using EtP2 as base
The reaction mixture was then stirred for 30 min at ^78ꢀC. After addition of water, the organic
phase was separated and the aqueous phase extracted with CH2Cl2. The dried combined organic
phases were concentrated under vacuum and then re-dissolved in a 1:1 mixture of Et2O:n-hexane.
The phosphazene-base salt (EtP2H+TfO^) which precipitated, was ®ltered o€ and the solution
concentrated under vacuum to give the crude product, which was analyzed before separation.

7311
It is worth noting that, with ylide 6a, the desired epoxides (1a,2a,3a)7 were always the major
product (Table 1, entries 1, 5, 6, 9 and 10), except in the case of aldehyde 7 in THF, which
provided up to 68% of other products identi®ed by NMR as being cyclopropanes8 (Table 1, entry
2). Aldehyde 9 and ylide 6a in THF also led to cyclopropanes,8 but as minor products (37%;
Table 1, entry 10). However, using CH2Cl2 instead of THF allowed us to maximize formation of
the epoxide, which was obtained as the major or sole product (100% for 3a and 77% for 1a;
Table 1, entries 1 and 9).
Interestingly, ylide 6b provided the epoxide (1b,2b or 3b)9 as the sole product with all
aldehydes regardless of the solvent. It thus appears that the methoxy group leading to a less
stabilized and more reactive ylide (6b) favors formation of the epoxide to the detriment of the
cyclopropanes, suggesting that the rate constants leading to formation of epoxides become large
compared to those leading to cyclopropanes.
When cis-epoxides are formed,10 higher percentages were obtained in CH2Cl2 than in THF
(Table 1, entries 3, 7 and 11). This is consistent with less reversibility in formation of the syn-
betaine in solvents of low polarity (CH2Cl2) compared to polar solvents (THF).11
The percentages of conversion12 were about 95% in all cases, as usually observed with this
method.1 However, while oxathiane 4 is almost fully recovered (ꢁ90% after puri®cation) and can
be reused, signi®cant amounts of epoxides are often lost during chromatography. This diculty
can be overcome through in situ opening13 (or further reaction) of these epoxides.
In all cases, the enantiomeric excesses14 (ee) obtained for the desired trans-isomers ranged from
95 to 100% (Table 1, entries 1, 4, 5, 8, 9 and 12). From the (+) sign of its optical rotation (in
EtOH), the trans-epoxide 3b was assigned the (R,R)-con®guration according to the literature.15
This is consistent with our previous results1,2a,6 and our model of approach of the reactants.6
Therefore, the (R,R)-con®guration can also be assigned to the other major trans-epoxides
obtained (1a,1b,2a,2b,3a).
Acknowledgements
Dr. A. Wick (Sylachim-Finorga, Paris) is gratefully acknowledged for encouragment and
®nancial support, and Prof. V. Sunjic for his help in ee % determinations.
References
1. (a) Solladie-Cavallo, A.; Diep-Vohuule, A.; Sunjic, V.; Vinkovic, V. Tetrahedron: Asymmetry 1996, 7, 1783±1788.
(b) Solladie-Cavallo, A.; Diep-Vohuule, A. J. Org. Chem. 1995, 60, 3494±3498.
2. (a) Solladie-Cavallo, A.; Diep-Vohuule, A.; Isarno, T. Angew. Chem., Int. Ed. 1998, 37, 1689±1691. (b) Corey,
E. J.; Jautelat, M. J. Am. Chem. Soc. 1967, 89, 3912±3914. (c) De Vos, M. J.; Krief, A. Tetrahedron Lett. 1983, 24,
103±106. (d) Calmes, M.; Daunis, J.; Escale, F. Tetrahedron: Asymmetry 1996, 7, 395±396.
3. Vedejs, E.; Engler, D. A.; Mullins, M. J. J. Org. Chem. 1977, 42, 3109±3113.
4. Isarno, T. Ph.D. Thesis, Strasbourg, 28 February 2000.
ꢀ
1
3
5. Compound 5b: m.p. 104±105 C; H NMR (200 MHz, CDCl3) ꢀ 0.97 (d, 3H, J=6.5 Hz, CH3), 1.1±1.3 (m, 3H),
1.55 (m, 1H), 1.70 (s, 3H, CH3), 1.75 (s, 3H, CH3), 1.8 (m, 2H), 2.05 (m, 1H), 3.78 (td, 1H, 3Jae=4 Hz, 3Jaa=3Jaa
=10 Hz, CH±O), 3.80 (s, 3H, methoxy), 4.61 (s, 2H, S+±CH2±Ph), 4.83 (A from AB, 1H, 2JAB=12 Hz,, S+±CH2±
2
O), 5.52 (B from AB, 1H, JAB=12 Hz, S+±H2±O), 6.92 (ꢁd, 2H arom., J=8.5 Hz), 7.42 (ꢁd, 2H arom., J=8.5
Hz); 13C NMR (50 MHz, CDCl3) ꢀ 21.0 (CH3), 21.8 (CH3), 23.6 (CH2), 25.8 (CH3), 30.9 (CH), 33.8, 36.1 (CH2),

7312
40.0 (S+±CH2±arom), 43.1 (CH), 55.5 (methoxy), 57.7 (O±CH2±S+), 70.7 (Cq(Me)2), 76.01 (O±CH), 115.3 (CH
arom.), 117.9 (Cq arom.), 132.3 (CH arom.), 161.0 (Cq arom.); IR (CHCl3) 1040 cm^1 (C±S+).
6. Solladie-Cavallo, A.; Adib, A.; Schmitt, M.; Fischer, J.; Decyan, A. Tetrahedron: Asymmetry 1992, 3, 1597±1602.
7. trans-Epoxides 1a,2a,3a: 1H NMR spectra are identical to those described in the literature, cf. (a) Lindstrom,
U. M.; Somfai, P. Synthesis 1998, 1, 109±117. (b) Frohn, M.; Dalkiewicz, M.; Tu, Y.; Wang, Z. X.; Shi, Y. J. Org.
Chem. 1998, 63, 2948±2953. (c) Aggarwal, V. K.; Ford, J. G.; Fonquerna, S.; Adams, H.; Jones, R. V. H.;
Fieldhouse, R. J. Am. Chem. Soc. 1998, 120, 8328±8339.
8. The signals of the epoxide ring (d and dd at 3.75 and 3 ppm, respectively) and of the cyclopropane ring (ddd at
2.05 ppm) have been used for identi®cation of compound 11 (R1=R2=H), while the signals of the cyclopropane
ring (ddd at 2.65, 2.20 and 1.75 ppm) and of the aldehyde (d at 9.35 ppm) have been used in the case of 12
(R1=R2=H). Similarly, 13 (R1=H, R2=Ph) was identi®ed from the epoxide ring signal (d at 3.75 ppm), and 14
(R1=H, R2=Ph) from the cyclopropane ring signal (ddd at 2.5 ppm) and the aldehyde (d at 8.95 ppm).
9. Compound 1b-trans-(R,R): 1H NMR (400 MHz, CDCl3) ꢀ 3.38 (dd, 1H, 3J=2 Hz, 3J=7.5 Hz, epoxide ring), 3.74
3
3
2
(d, 1H, J=2 Hz, epoxide ring), 3.83 (s, 3H, OMe), 5.35 (dd, 1H, Jcis=10.5 Hz, J=0.5 Hz, CH vinyl), 5.55
3
2
3
3
3
(dd, 1H, Jtrans=16 Hz, J=0.5 Hz, CH vinyl), 5.75 (ddd, 1H, J=7.5 Hz, Jcis=10.5 Hz, Jtrans=16 Hz, CH
vinyl), 6.91 (ꢁd, 2H, arom.), 7.22 (ꢁd, 2H, arom.); 13C NMR (100 MHz, CDCl3) ꢀ 55.7 (methoxy), 60.5 (epoxide
ring), 63.1 (epoxide ring), 114.4 (CH arom.), 119.7 (CH2 vinyl), 127.2 (CH arom.), 129.4 (Cq arom.), 135.6 (CH
vinyl), 160.2 (Cq arom.). Compound 2b-trans-(R,R): H NMR (400 MHz, CDCl3) ꢀ 1.81 (bs, 6H, (CH3)2), 3.53
(dd, 1H, 3J=2 Hz, 3J=8.5 Hz, epoxide ring), 3.73 (d, 1H, 3J=2 Hz, epoxide ring), 3.83 (s, 3H, OMe), 5.02 (sept.
1
d, 1H, J=8.5 Hz, J=4J=4J=4J=4J=4J=1 Hz, CH vinyl), 6.91 (ꢁd, 2H, arom.), 7.24 (ꢁd, 2H, arom.); 13C
NMR (100 MHz, CDCl3) ꢀ 18.8 (CH3 vinyl), 26.3 (CH3 vinyl), 55.7 (methoxy), 60.1 (epoxide ring), 60.3 (epoxide
ring), 114.4 (CH arom.), 122.4 (Cq vinyl), 127.1 (CH arom.), 129.9 (Cq arom.), 140.8 (CH vinyl), 160.0 (Cq
3
4
25
25
D
arom.). Compound 3b-trans-(R,R): mp=100±102ꢀC; ‰ꢁŠ +209 (c 1.0; CHCl3); ‰ꢁŠ +266 (c 0.31; EtOH); 1H
D
3
3
NMR (200 MHz, CDCl3) ꢀ 3.52 (dd, 1H, J=2.5 Hz, J=7.5 Hz, epoxide ring), 3.84 (s, 3H, OMe), 3.85 (d, 1H,
3J=2.5 Hz, epoxide ring), 6.07 (dd, 1H, 3J=7.5 Hz, 3J=16 Hz, CH vinyl), 6.81 (d, 1H, 3J=16 Hz, CH vinyl), 6.90
(ꢁd, 2H, arom.), 7.2±7.45 (m, 7H, arom.); 13C NMR (100 MHz, CDCl3) ꢀ 55.7 (methoxy), 61.0 (epoxide ring),
63.3 (epoxide ring), 114.5 (CH arom.), 126.7 (CH arom.), 126.9 (CH), 127.2 (CH arom.), 128.5 (CH), 129.1 (CH
arom.), 129.4 (Cq arom.), 134.7 (CH), 136.6 (Cq arom.), 160.2 (Cq arom.).
10. The coupling constants (larger for the cis-isomer, ꢁ5 Hz, compared to the trans-isomer, ꢁ2 Hz) have been
determined on the signals of the epoxide ring protons and have been used to identify the cis-epoxides.
11. Aggarwal, V. K.; Calamai, S.; Ford, J. G. J. Chem. Soc., Perkin Trans. 1 1997, 5, 593±600.
1
12. Percentages of conversion were determined on solvent-free crude products by combining weights and H NMR.
13. Solladie-Cavallo, A.; Roje, M.; Isarno, T.; Sunjic, V.; Vinkovic, V. Eur. J. Org. Chem. 2000, 1077±1080. Oxathiane
is inert to reduction and nucleophilic opening of epoxides.
14. Analytical chiral columns: Chiralcel OJ, Chiralcel OB-H and Chiralpack AS (all 25 cmÂ4.6 mm I.D., from Daicel,
Japan) were used. The mobile phases were iPrOH:hexane mixtures (10:90 to 3:97).
15. Imuta, M.; Zi€er, H. J. Org. Chem. 1979, 44, 2505±2509.