asc.wiley-vch.de
Table 1. [2+2+2] Cyclization of the enediyne 5 with the sys-
After one hour, a solution of enediyne 5 (0.52 mmol, 1 equiv)
in CH2Cl2 (3 mL) was added. The reaction was monitored by
TLC, and after completion, the reaction mixture was con-
centrated, filtered over celite, and purified by flash chroma-
tography.
tem [CoX2/Mn/phosphine][a]
Entry CoX2
(equiv)
Phosphine Solvent Time (h) Yield (%)[b]
(equiv)
1
2
3
4
5
6
7
8
9
CoI2 (1)
CoI2 (0.5) PPh3 (1)
CoI2 (2)
CoI2 (1)
PPh3 (2)
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
THF
CH2Cl2
THF
0.5
4
0.5
12
0.1
24
1
24
24
51
17
0
42
34
0
34
0
19
PPh3 (4)
dppe (1)
PPh3 (2)
PPh3 (2)
PPh3 (2)
PPh3 (2)
PPh3 (2)
References
CoI2 (1)
CoBr2 (1)
CoBr2 (1)
CoCl2 (1)
CoCl2 (1)
[1] For excellent reviews on metal-mediated cycloaddi-
tions, see: (a) M. Lautens, W. Klute, W. Tam, Chem.
Rev. 1996, 96, 49±92; (b) B. M. Trost, M. J. Krische,
Synlett 1998, 1±16; (c) I. Ojima, M. Tzamarioudaki,
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(d) D. B. Grotjahn in Comprehensive Organometallic
Chemistry II, Vol. 12 (Eds: F. W. Abel, F. G. A. Stone,
G. Wilkinson, L. S. Hegedus), Pergamon Press, New
York, 1995, pp. 741±770.
CH2Cl2
THF
[a] With respect to CoX2/Mn/phosphine = 1/10/2.
[b]
The reactions are monitored by TLC and, after comple-
tion, worked-up.
peared to be totally consumed, the yield of the cycli-
zation remained moderate. The removal of the cy-
cloadduct from the heterogeneous medium seems
to be the major problem of the reaction. Indeed, the
presence of an excess of manganese probably allows
associations with the gem-diester. Moreover, the use
of one equivalent of cobalt salt appears necessary to
drive the reaction to completion, suggesting the for-
mation of a very sensitive complexed form of the tri-
cyclic compound, which could be decomplexed and
decomposed during the purification. The exact nat-
ure of the catalyst intermediate is not yet known
and the cyclization could be promoted either by
Co(0) or Co(I) species.
In summary, these preliminary results show that
the system CoI2/Mn/PPh3 is able to catalyze success-
fully the intramolecular [2+2+2] cyclizations of
triynes at room temperature in very high yields. For
the first time, it has been shown that this combination
is also efficient for the cyclization of an enediyne in
which the olefinic partner is not activated. This sys-
tem is cheap, easy to handle, and employs phosphines
as well as diphosphines. The use of such ligands, as-
sociated to the fact that the free dienic compound is
directly isolated, bodes well for the success of the cat-
alytic asymmetric version of this reaction. These stu-
dies are currently under very active investigations in
our laboratories.
[2] B. M. Trost, Angew. Chem. 1995, 107, 285±307; Angew.
Chem. Int. Ed. Engl.1995, 34 259±281.
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hardt in Organic Synthesis Today and Tomorrow (Eds:
B. M. Trost, C. R. Hutchinson), Pergamon Press, Ox-
ford, 1981, 71±83; (c) K. P. C. Vollhardt, Pure & Appl.
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Vollhardt, J. Org. Chem. 1984, 49, 1564±1573; (e) T. R.
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Org. Chem. 1984, 49, 5010±5012; (g) E. P. Johnson,
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Experimental Section
The preparation and spectral data on compounds 1±5 and
12±16 are available as ªSupporting Informationº which is
available on the ASC website.
[9] I. F. Duan, C. H. Cheng, J. S. Shaw, S. S. Cheng, K. F.
Liou, J. Chem. Soc., Chem. Commun. 1991, 1347±1348.
[10] O. Pardigon, A. Tenaglia, G. Buono, J. Org. Chem.
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Met. Chem. 1984, 9, 360±362; (b) G. P. Chiusoli,
Typical Procedure for the Cyclization of 5
In a flask wrapped with aluminium foil, at room tempera-
ture, under argon, CoI2 (163 mg, 0.52 mmol, 1 equiv) was
added to a suspension of Mn (286 mg, 5.2 mmol, 10 equiv)
and PPh3 (273 mg, 1.04 mmol, 2 equiv) in CH2Cl2 (5 mL)
66
Adv. Synth. Catal. 2001, 343, 64±67