the cyclohexene template. The products of this study are under
evaluation as components for novel nucleoside and inositol
phosphate analogues as we learn more about the steric and
electronic effects of the mimetic group.
The authors wish to thank the Engineering and Physical
Sciences Research Council of Great Britain for support (Quota
Award to A. H. B).
Notes and references
† Selected data for 1: nmax (film)/cm21 3434br s, 1786s; dH(CDCl3, 300
2
MHz) 4.88–4.79 (m, 1H), 4.32–4.20 (m, 4H), 3.95 (dd, 1H, JH-H 12.5,
2
3
3JH-H 2.2), 3.65 (dd, 1H, JH-H 12.5, JH-H 2.6), 3.5 (br s, 1H, OH),
3.44–3.20 (m, 2H), 2.85 (dd, 1H, 2JH-H 18.8, 3JH-H 9.2), 2.77 (dd, 1H, 2JH-H
18.4, 3JH-H 7.0), 1.38 (t, 6H, 3JH-H 7.0); 13C dC(CDCl3, 75 MHz) 175.2 (s),
1
1
3
2
119.4 (td, JC-F 263.4, JC-P 214.8), 78.8 (q, JC-FNC-P 4.5), 65.4 (d, JC-P
6.8), 65.2 (d, 2JC-P 6.8), 63.4 (s), 40.3 (td, 2JC-F 20.9, 2JC-P 15.3), 29.1 (td,
3JC-F 5.1, 3JC-P 2.3), 16.4 (d, 3JC-P 5.7); dF(CDCl3, 282 MHz) 2116.8 (ddd,
2JF-F 342.1, 2JF-P 105.5, 3JF-H 16.5). 2117.99 (ddd, 2JF-F 343.3, 2JF-P 104.3,
3JF-H 17.8); dP(CDCl3, 121 MHz) 5.6 (t, 2JP-F 103.9 Hz); m/z (ES) 325 (M
+ Na, 100) HRMS calc. for C10H17O6F2NaP 325.0629, found 325.0632.
Anal. Calcd for C10H17O6F2P: C, 39.74, H, 5.70; found: C, 39.55, H,
5.45%.
Scheme 3 Reagents and conditions: i, Amberlyst-15, dry DCM, rt; ii,
CDCl3, rt, 18 h.
‡ Selected data for 2: nmax (film)/cm21 2987m, 1725s, 1684m; dH(CDCl3,
300 MHz) 6.10–5.89 (m, 2H), 4.25–4.10 (m, 4H), 3.39–3.19 (m, 1H), 2.89
(d, 1H, 2JH-H 22.4), 2.77 (d, 1H, 2JH-H 22.6), 2.71 (dd, 1H, 2JH-H 14.7, 3JH-H
6.6), 2.55 (dd, 1H, 2JH-H 15.1, 3JH-H 6.3), 1.28 (t, 6H, 3JH-H 6.3); dC(CDCl3,
75 MHz) 206.5 (s), 128.7 (s), 122.2–122.0 (m), 120.4 (td, 1JC-F 264.5, 1JC-P
211.9), 64.7 (t, 3JC-F 7.4), 41.9 (td, 2JC-F 21.5, 2JC-P 15.8), 39.1 (s), 37.5 (q,
3JCFNCP 5.1), 16.3 (d, JC-P 5.7); dF(CDCl3, 282 MHz) 2114.1 (ddd, JF-F
300.1, 2JF-P 105.5, 3JF-H 15.3), 2115.8 (ddd, 2JF-F 300.1, 2JF-P 109.8, 3JF-H
17.8); dP(CDCl3, 121 MHz) 6.0 (t, 2JF-P 106.8); m/z (ES) 305 (M + Na, 100);
HRMS calc. for C11H17O4F2P 305.0730, found 305.0722.
standing of this process is sought currently, but clearly the direct
cyclisation of 9b via nucleophilic attack involving the ester
carbonyl group is highly unfavourable.15
A change of tactics allowed access to an attractively
functionalised cyclohexenone (Scheme 4); vinylation of 3
protected the hydroxy group as 12 for the Shibuya–Yokomatsu
coupling allowing Dauben–Dietsche rearrangement16 to pro-
ceed affording enal 14.
3
2
1 T. Yokomatsu, Y. Hayakawa, K. Suemune, T. Kihara, S. Soeda, H.
Shimeno and S. Shibuya, Bioorg. Med. Chem. Lett., 1999, 9, 2833.
2 J. Matulic-Adamic, P. Haeberli and N. Usman, J. Org. Chem., 1995, 60,
2563.
3 A. S. Campbell and G. R. J. Thatcher, Tetrahedron Lett., 1991, 32,
2207.
4 K. Blades, A. H. Butt, G. S. Cockerill, H. J. Easterfield, T. P. Lequeux
and J. M. Percy, J. Chem. Soc., Perkin Trans. 1, 1999, 3609.
5 K. Blades, D. Lapoˆtre and J. M. Percy, Tetrahedron Lett., 1997, 38,
5895.
6 K. Blades and J. M. Percy, Tetrahedron Lett., 1998, 39, 9085.
7 M. Abarbi, J. Parran, J. Cintrat and A. Duchene, Synthesis, 1995, 82; I.
Marek, C. Mayer and J.-F. Normant, Org. Synth., 1996, 74, 194.
8 T. Yokomatsu, K. Suemune, T. Murano and S. Shibuya, J. Org. Chem.,
1996, 61, 7207.
9 We used the following procedure; R. Bao, S. Valverde and B. Herradon,
Synlett, 1992, 217.
10 D. A. Evans, G. C. Fu and A. H. Hoveyda, Chem. Rev., 1993, 93,
1307.
11 C. Cope´ret, H. Adolfsson and K. B. Sharpless, Chem. Commun., 1999,
1565.
12 D. Yang, M.-K. Wong and Y.-C. Yip, J. Org. Chem., 1995, 60, 3887.
13 The reaction was based upon the cyclisation reported by J. Cardellac, C.
Estopa, J. Font, M. Moreno-Man˜as, R. M. Ortun˜o, F. Sanchez-Ferrado,
S. Valle and L. Vilamajo, Tetrahedron, 1982, 28, 2377.
14 T. Yokomatsu, T. Sada, T. Shimizu and S. Shibuya, Tetrahedron Lett.,
1998, 39, 6299.
15 Iodolactonisation according to Ito et al. (H. Ito, A. Saito and T. Taguchi,
Tetrahedron Asymm., 1998, 9, 1979; I2, MeCN, rt, 18 h) of 7 afforded
exclusively the cis-iodolactone 19 (68%, stereochemistry assigned by
Scheme 4 Reagents and conditions: i, ethyl vinyl ether, Hg(OAc)2, reflux,
70%; ii, BrZnCF2PO(OEt)2, CuBr, DMF, 84%; iii, 140 °C, xylene, 75%; iv,
allylmagnesium bromide, ethyl ether, 60% (1+1 ratio); v, Grubbs’ catalyst,
DCM, reflux, 48 h; vi, allyltrimethylsilane, BF3·OEt2, DCM, rt, 83% (7+2
ratio); vii, PDC, DCM, rt.
Allylation under Grignard conditions afforded a pair (in a 1+1
ratio) of diastereoisomeric phosphodiesters 15a and 15b; slow
(48 h) RCM under standard Grubbs’ conditions17 then closed
the cis congener to yield 16 (64% by NMR) leaving the trans
isomer 15b unchanged. We inferred that cyclisation with loss of
ethanol had occurred after Grignard addition. Boron trifluoride-
catalysed (Sakurai) allylation with allyltrimethylsilane18 af-
forded homoallyl alcohols 17a and 17b in a 7+2 ratio
(unassigned) then RCM afforded a 7+2 mixture of cyclohex-
enols 18a and 18b which were converged by oxidation to 2‡
with PDC. Enone 2 contains a pattern of functional groups from
which four contiguous hydroxylated positions could be devel-
oped and we will explore its chemistry further.
GOESY); this process must follow a trajectory similar to that of the
closure of 9a to 1.
16 W. G. Dauben and T. J. Dietsche, J. Org. Chem., 1972, 37, 1212.
17 For a review, see R. H. Grubbs and S. Chang, Tetrahedron, 1998, 54,
4413.
The appeal of this strategy lies in the possibility of
asymmetric catalysis of the [3,3] rearrangement controlling the
absolute configuration of the mimetic-bearing carbon atom and
the potential for a high degree of subsequent stereocontrol on
18 A. Bottoni, A. L. Costa, D. DiTommaso, I. Rossi and E. Tagliavini,
J. Am. Chem. Soc., 1997, 119, 12131.
1692
Chem. Commun., 2000, 1691–1692