thienofuranones and displays excellent diastereoselectivity. We
have also shown that intramolecular Büchner reactions can
compete with ylide formation in such cases whereas 1,6-carbenoid
C–H insertion reactions do not.
We thank OSI Pharmaceuticals (PSS) and GlaxoSmithKline
(NAS) for CASE studentships and the Royal Society for a
University Research Fellowship (RCDB). We also acknowledge
Dr. M. E. Light and Prof. M. B. Hursthouse for X-ray structural
determination.
Scheme 3
Notes and references
1 For examples of oxygen activated C–H insertions, see: J. Adams and R.
Frenette, Tetrahedron Lett., 1987, 28, 4773; J. Adams, M. A. Poupart,
L. Grenier, C. Schaller, N. Ouimet and R. Frenette, Tetrahedron Lett.,
1989, 30, 1749.
2 For examples of nitrogen activated C–H insertions, see: T. C. Smale,
Tetrahedron Lett., 1984, 25, 2913; P. Brown and R. Southgate,
Tetrahedron Lett., 1986, 27, 247.
3 For reviews of diazo/carbenoid reactivity, see: M. P. Doyle, Chem. Rev.,
1986, 86, 919; J. Adams and D. M. Spero, Tetrahedron, 1991, 47,
1765–1808; A. Padwa and K. E. Krumpe, Tetrahedron, 1992, 48, 5385;
T. Ye and M. A. McKervey, Chem. Rev., 1994, 94, 1091; M. P. Doyle
and D. C. Forbes, Chem. Rev., 1998, 98, 911.
Fig. 1 Possible transition state model for C–H insertion to afford 2-endo-
substituted 7-oxa-3-thia-bicyclo[3.3.0]octanes.
interactions between R2, the C4 b-hydrogen and R increase when
R2 = Me. Therefore other pathways, including exo C–H insertion
and 1,2-insertion, to butenolide 8, become more important.
To conclude our study we examined two cases where 1,5-inser-
tion was not possible. Thus, exposure of phenyl sulfide 1h to
Rh2(OAc)4 gave cycloheptatriene 11 in high yield via an intra-
molecular Büchner reaction,15 while tert-butyl sulfide 1i gave
alcohol 12, presumably via hydrolysis of sulfonium ylide 10
(Scheme 4). No products derived from 1,6-carbenoid C–H insertion
were observed in either reaction.
4 A. Padwa and S. F. Hornbuckle, Chem. Rev., 1991, 91, 263.
5 A. Padwa, S. F. Hornbuckle, G. E. Fryxell and P. D. Stull, J. Org.
Chem., 1989, 54, 817.
6 For formation of a four-membered cyclic sulfonium ylide, see: H. M. L.
Davies and L. V. Crisco, Tetrahedron Lett., 1987, 28, 371.
7 Other examples of cyclisation reactions being biased towards an
abnormal course through the inclusion of a five membered ring in the
tethering chain include: D. C. Harrowven, N. L’Helias, J. D. Moseley,
N. J. Blumire and S. R. Flanagan, Chem. Commun., 2003, 2658; J. W.
Dankwardt and L. A. Flippin, J. Org. Chem., 1995, 60, 2312.
8 R. J. Clemens and J. A. Hyatt, J. Org. Chem., 1985, 50, 2431.
9 B. B. Snider and B. A. McCarthy, Tetrahedron, 1993, 49, 9447; M. P.
Bertrand, H. O. Mahamat, C. Moustrou and J. M. Surzur, J. Org. Chem.,
1989, 54, 5684.
In summary, we have shown that 1,5-carbenoid C–H insertion
reactions adjacent to sulfur may proceed efficiently and outpace
ylide formation when the latter leads to a strained bicyclic ring
system. The method has been used to synthesise a series of
10 C. S. Lee, K. I. Lee and A. D. Hamilton, Tetrahedron Lett., 2001, 42,
211; C. S. Lee, K. I. Lee and A. D. Hamilton, Tetrahedron Lett., 2001,
42, 2929.
11 N. A. Swain, R. C. D. Brown and G. Bruton, J. Org. Chem., 2004, 69,
122; R. C. D. Brown, C. J. R. Bataille, G. Bruton, J. D. Hinks and N. A.
Swain, J. Org. Chem., 2001, 66, 6719.
12 Procedure for the rhodium-catalysed C–H insertion of compound 1a: To
a solution of diazolactone 1a (58 mg, 0.18 mmol) in CH2Cl2 (4 mL) at
room temperature was added Rh2(OAc)4 (2 mg, 2 mol%) and the
resulting pink, slowly effervescing (N2) reaction mixture was stirred for
24 h. The reaction was concentrated in vacuo to afford crude
furofuranone as a pink gum (61 mg). Purification (SiO2) eluting with
10–20% EtOAc in hexane gave compound 2a as a white crystalline solid
(38 mg, 0.13 mmol, 72%); mp 136–138 °C (EtOAc/hexane); nmax
(neat)/cm21 1761; dH (400 MHz, CDCl3) 7.43–7.30 (10H, m, PhH),
5.43 (1H, d, J 6.9, PhCHO–), 4.87 (1H, d, J 9.0, PhCHS–), 3.58 (1H, t,
J 9.0, –O2CCH–), 3.41 (1H, dddd, J 9.0, 6.9, 5.8, 1.0, –SCH2CH–), 3.27
(1H, dd, J 12.6, 5.8, –SCHH–), 3.08 (1H, d, J 12.6, –SCHH–); dC (100
MHz, CDCl3) 174.5, 139.5, 135.4, 129.1, 128.9, 128.9, 128.7, 128.5,
125.8, 85.2, 56.8, 54.6, 53.9, 37.0; m/z (CI) 314 ([MNH4]+, 100%), 297
([MH]+, 96).
13 The stereochemistry of 2a was determined by X-ray crystallography;
details to be published elsewhere.
14 M. P. Doyle, L. J. Westrum, W. N. E. Wolthuis, M. M. See, W. P.
Boone, V. Bagheri and M. M. Pearson, J. Am. Chem. Soc., 1993, 115,
958.
Scheme 4
15 E. Büchner and T. Curtius, Chem. Ber., 1885, 18, 2374.
C h e m . C o m m u n . , 2 0 0 4 , 1 7 7 2 – 1 7 7 3
1773