LETTER
New Insights into the Enyne-Metathesis Mechanism
2381
OTBS
(m, 2 H), 1.57–1.50 (m, 1 H), 0.84 (s, 9 H), 0.06 (s, 3 H), 0.03 (s, 3
1
3
cat. I (5 mol%)
H). C NMR (100.6 MHz, CDCl ): d = 163.4, 146.0, 139.2, 136.8,
3
3
114.3, 84.2, 71.7, 36.6, 28.8, 26.1, 19.4, 18.3, –4.1, –4.6. MS (DI,
CH2Cl2, 40 °C
O
O
–1
O
CI NH ): m/z = 295, 249. IR: 2928, 2856, 1719, 1632 cm .
3
36%
TBSO
9
10
All new compounds gave satisfactory spectroscopic and analytical
data.
O
Scheme 7
Acknowledgment
In conclusion, we have uncovered further evidence to
confirm that the alkyne first pathway should be the
favored process in enyne metathesis. Moreover, to the
best of our knowledge, this is the first time that steric
hindrance at the propargylic position was proven to be of
importance in the outcome of this reaction.
We thank Dr. J. A. Funel and Dr. J. Prunet for fruitful discussions.
E.V. and J.O. thank the MENR for a fellowship. Financial support
was provided by the ENSTA.
References
(
1) (a) David, J. P.; Santos, A. J.; Guedes, M. L.; David, J. M.;
Chai, H.-B.; Pezzuto, J. M.; Angerhofer, C. K.; Cordell, G.
A. Pharm. Biol. 1999, 37, 165. (b) This molecule had been
previously isolated from Ambrosia dumosa in 1979, see:
Seaman, F. C.; Mabry, T. J. Rev. Latinoam. Quim. 1979, 10,
85.
Typical Procedure for Metathesis
The reaction was performed in a 25 mL Schlenk equipped with a
condenser. A solution of the enyne in CH Cl was degassed once
2
2
under Ar. The catalyst I (5 mol%) was added and the mixture was
heated at 40 °C overnight. Solvent is removed in vacuo and the
crude product was purified by flash silica gel column chromato-
graphy.
(2) Likhitwitayawuld, K.; Angerhofer, C. K.; Cordell, G. A.;
Pezzuto, J. M.; Ruangrungsi, N. J. Nat. Prod. 1993, 56, 30.
(3) (a) Kingsbury, J. S.; Harrity, J. P. A.; Bonitatebus, P. J. Jr.;
Hoveyda, A. H. J. Am. Chem. Soc. 1999, 121, 791.
(b) Garber, S. B.; Kingsbury, J. S.; Gray, B. L.; Hoveyda, A.
H. J. Am. Chem. Soc. 2000, 122, 8168. (c) Gessler, S.;
Randl, S.; Blechert, S. Tetrahedron Lett. 2000, 41, 9973.
(4) For recent reviews on enyne metathesis, see: (a) Diver, S.
T.; Giessert, A. J. Chem. Rev. 2004, 104, 1317. (b) Poulsen,
C. S.; Madsen, R. Synthesis 2003, 1.
(5) For a discussion concerning enyne metathesis mechanism,
see: (a) Kinoshita, A.; Mori, M. Synlett 1994, 1020.
(b) Stragies, R.; Schuster, M.; Blechert, S. Angew. Chem.,
Int. Ed. Engl. 1997, 36, 2518. (c) For a more recent study,
see: Galan, B. R.; Giessert, A. J.; Keister, J. B.; Diver, S. T.
J. Am. Chem. Soc. 2005, 127, 5762.
(6) Recently, in contrast to our results, Diver and co-workers
suggested that more substituted alkynes gave faster
reactions: Galan, B. R.; Giessert, A. J.; Keister, J. B.; Diver,
S. T. J. Am. Chem. Soc. 2005, 127, 5762.
(7) According to NMR spectra, regioisomer 2 seemed to be
isolated as one single stereoisomer whose configuration was
not determined.
Spectroscopic Data for Compound 8
1
H NMR (400 MHz, CDCl ): d = 6.22 (dd, J = 17. 8, 11.2 Hz, 1 H),
3
5
.95 (dd, J = 8.2, 5.5 Hz, 1 H), 5.10 (d, J = 17.8 Hz, 1 H), 4.92 (d,
J = 11.2 Hz, 1 H), 4.52 (s, 1 H), 3.58 (dd, J = 10.9, 3.5 Hz, 1 H),
.55 (dt, J = 13.3, 5.5 Hz, 1 H), 2.36–2.25 (m, 1 H), 1.95 (dd,
J = 13.3, 8.2 Hz, 1 H), 1.72–1.60 (m, 2 H), 1.41–1.33 (m, 1 H), 0.89
2
1
3
(
s, 18 H), 0.10 (s, 3 H), 0.07 (s, 3 H), 0.04 (s, 3 H), 0.03 (s, 3 H).
C
NMR (100.6 MHz, CDCl ): d = 141.3, 140.0, 137.1, 110.0, 74.1,
3
7
3.8, 34.6, 30.1, 26.9, 26.4, 26.2, 18.7, 18.5, –4.1, –4.2, –4.4, –4.5.
MS (DI, CI NH ): m/z = 382, 268, 251, 223. IR: 2926, 2855, 1472
3
–
1
cm .
Spectroscopic Data for Compound 8¢
1
H NMR (400 MHz, CDCl ): d = 7.22 (d, J = 15.9 Hz, 1 H), 6.39
3
(
dd, J = 8.3, 5.8 Hz, 1 H), 5.81 (d, J = 15.9 Hz, 1 H), 4.47 (s, 1 H),
3
.76 (s, 3 H), 3.57 (dd, J = 11.2, 3.5 Hz, 1 H), 2.61 (dt, J = 12.9, 5.8
Hz, 1 H), 2.29 (q, J = 11.2 Hz, 1 H), 2.07 (dd, J = 12.9, 8.3 Hz, 1
H), 1.77–1.63 (m, 2 H), 1.44–1.39 (m, 1 H), 0.89 (s, 9 H), 0.88 (s, 9
1
3
H), 0.11 (s, 3 H), 0.06 (s, 3 H), 0.05 (s, 3 H), 0.03 (s, 3 H). C NMR
(
100.6 MHz, CDCl ): d = 168.0, 148.1, 146.1, 139.8, 114.1, 74.2,
(8) (a) This could be done in a one-step procedure according to
our previous work (see ref. 8b) or in a two-step procedure
(see ref. 8c). (b) Royer, F.; Vilain, C.; El Kaïm, L.; Grimaud,
L. Org. Lett. 2003, 5, 2007. (c) Cesati, R. R.; De Armas, J.;
Hoveyda, A. H. J. Am. Chem. Soc. 2004, 126, 96.
(9) (a) Choi, T.-L.; Grubbs, R. H. Chem. Commun. 2001, 2648.
(b) Boyer, F.-D.; Hanna, I.; Ricard, L. Org. Lett. 2004, 6,
1817.
3
7
–
1
3.3, 51.1, 34.3, 27.1, 26.3, 26.2, 25.2, 18.7, 18.5, –4.1, –4.2, –4.4,
4.5. MS (DI, CI NH ): m/z = 441, 257. IR: 2928, 2856, 1724, 1623,
3
–
1
472 cm .
Spectroscopic Data for Compound 10
1
H NMR (400 MHz, CDCl ): d = 6.85 (d, J = 9.5 Hz, 1 H), 6.23 (dd,
3
J = 8.8, 5.8 Hz, 1 H), 5.68 (d, J = 9.5 Hz, 1 H), 5.44 (s, 1 H), 5.21–
5
.18 (m, 1 H), 2.46–2.38 (m, 1 H), 2.14–2.01 (m, 2 H), 1.87–1.67
Synlett 2005, No. 15, 2379–2381 © Thieme Stuttgart · New York