ROM of the norbornene before the RCM reactions (both
olefin and enyne) occurred. The tandem domino meta-
thesis–Diels–Alder strategy is currently being used in the
preparation of skeletally diverse small molecule collections.
We acknowledge the EPSRC, BBSRC and Augustus and
Harry Newman Foundation and Lilly for generous support.
We also acknowledge the EPSRC National Mass Spectro-
metry Service Centre, Swansea, for providing mass
spectrometric data.
Scheme 6 Ring closing metathesis gave both exo and endo cyclized
products (9 and 11, respectively), but only the exo isomer was able to
react with the dienophile to give 12.
Notes and references
1. For recent reviews on DOS see: (a) T. E. Nielsen and S. L. Schreiber,
Angew. Chem., Int. Ed., 2008, 47, 48–56; (b) D. S. Tan, Nat. Chem.
Biol., 2005, 1, 74–84; (c) R. J. Spandl, D. R. Spring and A. Bender,
Org. Biomol. Chem., 2008, 6, 1149–1158; (d) G. L. Thomas,
E. E. Wyatt and D. R. Spring, Curr. Opin. Drug Discovery Dev.,
2006, 9, 700–712 and references therein.
2. Selected recent examples: (a) S. K. Ko, H. J. Jang, E. Kim and
S. B. Park, Chem. Commun., 2006, 2962–2964; (b) E. E. Wyatt,
S. Fergus, W. R. J. D. Galloway, A. Bender, D. J. Fox,
A. T. Plowright, A. S. Jessiman, M. Welch and D. R. Spring,
Chem. Commun., 2006, 3296–3298; (c) G. L. Thomas,
R. J. Spandl, F. G. Glansdorp, M. Welch, A. Bender,
J. Cockfield, J. A. Lindsay, C. Bryant, D. F. J. Brown,
O. Loiseleur, H. Rudyk, M. Ladlow and D. R. Spring, Angew.
Chem., Int. Ed., 2008, 47, 2808–2812.
3. For a recent review see: R. J. Spandl, G. L. Thomas, M. Diaz-
Gavilan, K. M. G. O’Connell and D. R. Spring, Chem. Rec., 2008,
DOI: 10.1002/tcr.20144, and references therein.
4. For recent reviews see: (a) S. G. Aitken and A. D. Abell, Aust.
J. Chem., 2005, 58, 3–13; (b) S. J. Connon and S. Blechert,
Angew. Chem., Int. Ed., 2003, 42, 1900–1923. For
example see: (c) C. K. Malik and S. Ghosh, Org. Lett., 2007, 9,
2537–2540.
a recent
Scheme 7 Optimized Diels–Alder conditions.
converted directly to the adduct 15 in ‘one-pot’ (Scheme 8). An
alternative substrate, with trans-norbornene architecture, was
also investigated. Although 16 performed well in the initial
metathesis process, the selectivity in the Diels–Alder reaction
step was reduced; both 17 and 18 (which resulted from endo-/
top and endo-/bottom face attack, respectively) were formed.
In conclusion, we have developed an efficient process to
convert decorated norbornenes into complex polycyclic sys-
tems. It is notable that the choice of Grubbs’ metathesis
catalyst affected the reaction pathway, the product distribu-
tion, and the yield. Optimum results were obtained when
catalysts 1 and 2 were used in a stepwise fashion, to facilitate
5. (a) O. Arjona, A. G. Csaky, M. C. Murcia and J. Plumet,
Tetrahedron Lett., 2000, 41, 9777–9779; (b) M. Mori,
H. Wakamatsu, Y. Sato and R. Fujita, J. Mol. Catal. A: Chem.,
2006, 254, 64–67.
6. (a) T. Kitamura, Y. Kuzuba, Y. Sato, H. Wakamatsu, R. Fujita
and M. Mori, Tetrahedron, 2004, 60, 7375–7389; (b) S. Randl,
N. Lucas, S. J. Connon and S. Blechert, Adv. Synth. Catal., 2002,
344, 631–633.
7. For selected examples see: (a) D. Banti, E. Groaz and M. North,
Tetrahedron, 2004, 60, 8043–8052; (b) E. Groaz, D. Banti and
M. North, Eur. J. Org. Chem., 2007, 3727–3745 and references therein.
8. For recent reviews on enyne metathesis see: (a) H. Villar, M. Frings
and C. Bolm, Chem. Soc. Rev., 2007, 36, 55–66; (b) S. T. Diver and
A. J. Giessert, Chem. Rev., 2004, 104, 1317–1382.
9. M. Mori, Adv. Synth. Catal., 2007, 349, 121–135.
10. The selectivity problem in enyne metathesis has been reported/ad-
dressed previously: (a) T. Kitamura, Y. Sato and M. Mori, Adv. Synth.
Catal., 2002, 344, 678–693; (b) E. C. Hansen and D. S. Lee, Acc. Chem.
Res., 2006, 39, 509–519; (c) T. Kitamura, Y. Sato and M. Mori, Chem.
Commun., 2001, 1258–1259; (d) E. C. Hansen and D. S. Lee, J. Am.
Chem. Soc., 2004, 126, 15074-15080, 2004, 126, 15074–15080.
11. In the formation of 6- and 7-membered rings the ene-then-yne
pathway yields the smaller exo ring isomer B(n).
10a This pathway is
supported by: (a) G. C. Lloyd-Jones, R. G. Margue and J. G. de
Vries, Angew. Chem., Int. Ed., 2005, 44, 7442–7447. For a recent
review see: (b) S. T. Diver, Coord. Chem. Rev., 2007, 251, 671–701.
12. T. L. Choi and R. H. Grubbs, Angew. Chem., Int. Ed., 2003, 42,
1743–1746.
13. Full details including reaction yields and spectral data can be
found in the ESIz.
14. Observed previously: O. Arjona, A. G. Csaky, V. Leon, R. Medel
and J. Plumet, Tetrahedron Lett., 2004, 45, 565–567.
15. (a) D. S. Lee, J. K. Sello and S. L. Schreiber, Org. Lett., 2000, 2,
709–712; (b) B. R. Galan, K. P. Kalbarczyk, S. Szczepankiewicz,
J. B. Keister and S. T. Diver, Org. Lett., 2007, 9, 1203–1206;
(c) E. Comer, E. Rohan, L. Deng and J. A. Porco, E. Comer, E.
Rohan, L. Deng, J. A. Porco, Org. Lett., 2007, 9, 2123–2126.
16. (a) J. J. Lippstreu and B. F. Straub, J. Am. Chem. Soc., 2005, 127,
7444–7457; (b) a more detailed discussion can be found in section
3 of the ESIz.
Scheme
reactions.
8 ‘One-pot’, tandem domino metathesis–Diels–Alder
ꢀc
This journal is The Royal Society of Chemistry 2008
Chem. Commun., 2008, 3001–3003 | 3003