functionalities and steric bulk tolerated by this reaction,
combined with the high yields obtainable for these cyclisations,
make this a valuable addition to the procedures currently
available for synthesising such complex b-lactam structures.
Further applications of alkene and enyne metathesis will be
reported in due course.
We thank Glaxo Wellcome Research Ltd. for the most
generous endowment (to A. G. M. B.) and for a CASE grant (to
S. P. D. B.), the Wolfson Foundation for establishing the
Wolfson Centre for Organic Chemistry in Medical Science at
Imperial College, and the Engineering and Physical Sciences
Research Council for studentships (to S. P. D. B. and K. F.).
Table 1 Enyne metathesis using ruthenium carbene 1a
Entry
Enyne
Product
1 (Mol%) Yieldb
(%)
H
1
0
0
1
N
N
N
10
O
O
O
Footnotes
H
11
2b
† E-mail: m.stow@ic.ac.uk
‡ E-mail: v.gibson@ic.ac.uk
§ All new compounds were fully characterised by spectroscopic data,
microanalysis and/or HRMS.
1
5
20
Me
N
2
52
88
O
10
Me
12
2c
¶ Typical experimental procedure: to enyne 2c (50 mg, 0.30 mmol) was
added a solution of catalyst 1 (21 mg, 0.03 mmol) in CH2Cl2 (3 ml). The
solution was heated to reflux for 3 h, concentrated and chromatographed on
silica (4:1 diethyl ether–hexane) to produce carbacephem 12 (44 mg, 88%)
as a colourless oil.
3
10
82
N
N
Me
Me
O
O
O
Me
Me
3b
13
O
O
4
10
10
88
70
N
N
N
O
14
4b
Ts
N
Ts
N
References
5
N
1 P. Schwab, M. B. France, J. W. Ziller and R. H. Grubbs, Angew. Chem.,
Int. Ed. Engl., 1995, 34, 2039.
Me
O
O
Me
2 R. R. Schrock, J. S. Murdzek, G. C. Bazan, J. Robbins, M. DiMare and
M. O’Regan, J. Am. Chem. Soc., 1990, 112, 3875.
3 For a recent review, see R. H. Grubbs, S. J. Miller and G. C. Fu, Acc.
Chem. Res., 1995, 28, 446.
15
5b
OSiMe2But
OSiMe2But
Me
6
10
15
100
72
4 For example, see D. Schinzer, A. Limberg, A. Bauer, O. M. Bo¨hm and
M. Cordes, Angew. Chem., Int. Ed. Engl., 1997, 36, 523; Z. Yang, Y. He,
D. Vourloumis, H. Vallberg and K. C. Nicolaou, Angew. Chem., Int. Ed.
Engl., 1997, 36, 166; R. E. Taylor and J. D. Haley, Tetrahedron Lett.,
1997, 38, 2061; F. P. J. T. Rutjes and H. E. Shoemaker, Tetrahedron Lett.,
1997, 38, 677; J. S. Clark and J. G. Kettle, Tetrahedron Lett., 1997, 38,
123; A. Fu¨rstner and K. Langemann, J. Org. Chem., 1996, 61, 8746;
P. Bertinato, E. J. Sorensen, D. Meng and S. J. Danishefsky, J. Org.
Chem., 1996, 61, 8000; A. G. M. Barrett, J. C. Beall, V. C. Gibson,
M. R. Giles and G. L. P. Walker, Chem. Commun., 1996, 2229;
H. S. Overkleeft and U. K. Pandit, Tetrahedron Lett., 1996, 37, 547.
5 A. Kinoshita and M. Mori, J. Org. Chem., 1996, 61, 8356; A. Kinoshita
and M. Mori, Synlett, 1994, 1020.
6 A. G. M. Barrett, S. P. D. Baugh, V. C. Gibson, M. R. Giles,
E. L. Marshall and P. A. Procopiou, Chem. Commun., 1996, 2231.
7 A. G. M. Barrett, S. P. D. Baugh, V. C. Gibson, M. R. Giles,
E. L. Marshall and P. A. Procopiou, Chem. Commun., 1997, 155.
8 For the preparation of 3a, see J. H. Bateson, A. J. G. Baxter,
P. M. Roberts, T. C. Smale and R. Southgate, J. Chem. Soc., Perkin
Trans. 1, 1981, 3242.
N
O
N
O
Me
16
OSiMe2But
6b
OSiMe2But
7
8
OSiMe2But
N
O
N
O
O
OSiMe2But
6c
17
O
Me
O
N
Me
5
48
74
N
10
O
9
18
OSiMe2But
O
O
O
OSiMe2But
9
10
82
N
N
O
10
19
9 A. Basak and U. Khamrai, Synth. Commun., 1994, 24, 131.
a
All reactions carried out on ca. 0.25 mmol scale as a 0.1 m solution in
b
CH2Cl2 with catalyst for 3 h. Isolated yield after column chromato-
graphy.
Received in Cambridge, UK, 30th April 1997; 7/02952G
1376
Chem. Commun., 1997