case (eqn (2)). Unfortunately, extending this chemistry to
2-tert-butylfuran provided the corresponding product 29 as an
equal mixture of regioisomers (eqn (3)). Finally, in an effort to
explore potentially more regioselective benzyne cycloaddition
chemistry, we opted to examine the reactions of substrates
23a,b that contain an o-bromo substituent (eqn (4); only one
regioisomer of substrate shown for clarity). Indeed, carrying
out azide cycloaddition with the in situ generated benzyne
intermediate provided the corresponding triazole 30 in modest
yield, but as a 4 : 1 mixture of regioisomers. The identity of the
major regioisomer suggests that the reaction proceeds under
steric control.18
Org. Lett., 2002, 4, 2767; (c) D. Pena, S. Escudero, D. Pe
E. Guitian and L. J. Castedo, Angew. Chem., Int. Ed., 1998, 37,
2659.
´
rez,
´
10 For the use of alkynylboronates in pericyclic reactions see:
(a) J. E. Moore, K. M. Goodenough, D. Spinks and J. P. A.
Harrity, Synlett, 2002, 2071; (b) J. E. Moore, M. W. Davies,
K. M. Goodenough, R. A. J. Wybrow, M. York, C. N. Johnson
and J. P. A. Harrity, Tetrahedron, 2005, 61, 6707; (c) J. E. Moore,
M. York and J. P. A. Harrity, Synlett, 2005, 860; (d) M. D. Helm,
J. E. Moore, A. Plant and J. P. A. Harrity, Angew. Chem., Int. Ed.,
2005, 44, 3889; (e) P. M. Delaney, J. Huang, S. J. F. Macdonald
and J. P. A. Harrity, Org. Lett., 2008, 10, 781; (f) D. L. Browne,
M. D. Helm, A. Plant and J. P. A. Harrity, Angew. Chem., Int. Ed.,
2007, 46, 8656; (g) D. L. Browne, J. F. Vivat, A. Plant, E. Gomez-
Bengoa and J. P. A. Harrity, J. Am. Chem. Soc., 2009, 131, 7762;
(h) J. Huang, S. J. F. Macdonald and J. P. A. Harrity, Chem.
Commun., 2009, 436.
11 For recent metal mediated or catalysed processes see:
(a) M. W. Davies, C. N. Johnson and J. P. A. Harrity, J. Org.
Chem., 2001, 66, 3525; (b) V. Gandon, D. Leca, T. Aechtner,
K. P. C. Vollhardt, M. Malacria and C. Aubert, Org. Lett., 2004, 6,
3405; (c) V. Gandon, D. Leboeuf, S. Amslinger, K. P. C.
Vollhardt, M. Malacria and C. Aubert, Angew. Chem., Int. Ed.,
In conclusion, we demonstrate that the [4+2] cycloaddition
of silyl-substituted alkynylboronate 9 with 2-pyrones followed
by C–B bond oxidation and trifluoromethylsulfonylation
provides an effective means for the synthesis of a range of
functionalised benzyne precursors. Studies towards extending
the scope of this strategy are underway and will be reported in
due course.
2005, 44, 7114; (d) A. Geny, D. Leboeuf, G. Rouquie,
´
K. P. C. Vollhardt, M. Malacria, V. Gandon and C. Aubert,
Chem.–Eur. J., 2007, 13, 5408; (e) G. Hilt and K. I. Smolko,
Angew. Chem., Int. Ed., 2003, 42, 2795; (f) G. Hilt, S. Luers and
K. I. Smolko, Org. Lett., 2005, 7, 251; (g) Y. Yamamoto, J.-i. Ishii,
H. Nishiyama and K. Itoh, J. Am. Chem. Soc., 2004, 126, 3712;
(h) Y. Yamamoto, J.-i. Ishii, H. Nishiyama and K. Itoh,
Tetrahedron, 2005, 61, 11501; (i) Y. Yamamoto, K. Hattori,
J.-i. Ishii and H. Nishiyama, Tetrahedron, 2006, 62, 4294;
We are grateful to the EPSRC and sanofi-aventis for
financial support.
Notes and references
1 (a) F. Shi, J. P. Waldo, Y. Chen and R. C. Larock, Org. Lett.,
2008, 10, 2409; (b) Z. Liu, F. Shi, P. D. G. Martinez, C. Raminelli
and R. C. Larock, J. Org. Chem., 2008, 73, 219; (c) M. Dai,
Z. Wang and S. J. Danishefsky, Tetrahedron Lett., 2008, 49, 6613;
(d) X.-C. Huang, Y.-L. Liu, Y. Liang, S.-F. Pi, F. Wang and
J.-H. Li, Org. Lett., 2008, 10, 1525.
2 (a) C. Raminelli, Z. Liu and R. C. Larock, J. Org. Chem., 2006, 71,
4689; (b) A. A. Cant, G. H. V. Bertrand, J. L. Henderson, L. Roberts
and M. F. Greaney, Angew. Chem., Int. Ed., 2009, 48, 5199.
3 (a) J. L. Henderson, A. S. Edwards and M. F. Greaney, J. Am.
Chem. Soc., 2006, 128, 7426; (b) S. A. Worlikar and R. C. Larock,
J. Org. Chem., 2009, 74, 9132; (c) S. A. Worlikar and R. C. Larock,
Org. Lett., 2009, 11, 2413; (d) Z. Qiu and C. Xie, Angew. Chem.,
Int. Ed., 2009, 48, 5729; (e) C. Xie, L. Liu, Y. Zhang and P. Xu,
Org. Lett., 2008, 10, 2393.
4 (a) K. Okuma, A. Nojima, N. Matsunaga and K. Shioji, Org. Lett.,
2009, 11, 169; (b) D. G. Pintori and M. F. Greaney, Org. Lett.,
2010, 12, 168.
5 G. Wittig and R. W. Hoffman, Org. Synth., 1971, Coll. Vol. V, 60.
6 T. Kitamura, K. Wasai, M. Todaka and Y. Fujiwara, Synlett,
1999, 731.
7 Y. Himeshima, T. Sonoda and H. Kobayashi, Chem. Lett., 1983, 1211.
8 For recent synthetic approaches to this compound: (a) S. M. Bronner
and N. K. Garg, J. Org. Chem., 2009, 74, 8842; (b) D. J. Atkinson,
J. Sperry and M. A. Brimble, Synthesis, 2010, 911.
´ ´
9 (a) D. Pena, D. Perez, E. Guitian and L. J. Castedo, J. Am. Chem.
Soc., 1999, 121, 5827; (b) H. Yoshida, S. Sugiura and A. Kunai,
(j) J. Barluenga, P. Barrio, L. Riesgo, L. A. Lo
M. Tomas, J. Am. Chem. Soc., 2007, 129, 14422.
´
´
pez and
12 (a) P. M. Delaney, J. E. Moore and J. P. A. Harrity, Chem.
Commun., 2006, 3323; (b) P. M. Delaney, D. L. Browne,
H. Adams, A. Plant and J. P. A. Harrity, Tetrahedron, 2008, 64,
866.
13 K. Afarinkia, M. J. Bearpark and A. Ndibwami, J. Org. Chem.,
2005, 70, 1122.
14 K. Afarinkia, M. J. Bearpark and A. Ndibwami, J. Org. Chem.,
2003, 68, 7158.
15 (a) C.-G. Cho, J.-S. Park, I.-H. Jung and H. Lee, Tetrahedron
Lett., 2001, 42, 1065; (b) G. H. Posner, K. Afarinkia and H. Dai,
Org. Synth., 1995, 73, 231.
16 (a) V. Kvita and H. Sauter, Helv. Chim. Acta, 1990, 73, 883;
(b) I. W. Ashworth, M. C. Bowden, B. Dembofsky, D. Levin,
W. Moss, E. Robinson, N. Szczur and J. Virica, Org. Process Res.
Dev., 2003, 7, 74.
17 Oxidation and protodesilylation of compounds 10a,b provided a
mixture of m- and p-chlorophenols, thereby providing a means to
determine the identity of the product regioisomers by 1H NMR
spectroscopy. See ESIw for details.
18 Assignment of product regiochemistry of compounds 24 and 26
was not carried out, however the regiochemical assignment of
compound 30a was determined by a nOe spectroscopy experiment.
ꢀc
This journal is The Royal Society of Chemistry 2010
5156 | Chem. Commun., 2010, 46, 5154–5156