Information.11 We were unable to drive the reaction to
completion by increasing nitrile stoichiometry (1.5-5.0
equiv). When 25 mol % of 2 was used, only 17% conversion
was observed. Due to the hindered nature of these sub-
strates,12 we postulated that catalyst decomposition may be
competitive. Accordingly, we attempted to stabilize CpCo(I).
Surprisingly, a dramatic solvent effect was noted, despite
the reports of nonpolar, noncoordinating solvents as being
optimal in these reactions. 1,2-Dimethoxyethane (entry 3),
1,2-dichloroethane (entry 4), 2-methyltetrahydrofuran (entry
9), and THF (entry 10) all resulted in catalytic reactions using
25 mol % of 2. Attempts to stabilize CpCo(I) further by
introducing chelating ligands resulted in lower conversions
relative to the control reaction in THF, suggesting a possible
trade-off between ligand stabilization and substrate coordina-
tion (entries 11-15).13 Gratifyingly, when the reaction was
performed in THF in the absence of irradiation, conversion
increased to >95%. Attempts to reduce the temperature
abolished catalytic activity, which is expected due to the
stability of the CO ligands. NiCl2(dppp)/Zn,14 CoCl2/Zn,15
and RhCl(PPh3)3,16 resulted in recovery of starting materials
or complex mixtures of products.
6
CpCo(ethylene)2 ) exist that liberate active catalyst under
milder conditions, but these precatalysts are difficult to
handle.7 While studies have explored the effect of altering
the ligand sphere around cobalt,8 the effect of exogenous
ligands and solvents on catalyst performance has not been
studied extensively.9
When 110 was treated with 2-methoxy-5-pyridinecarbo-
nitrile and stoichiometric CpCo(CO)2 2 in xylenes (140 °C,
200 W irradiation), a moderate conversion to 5 was achieved
(Table 1, entry 1), while the regioisomeric pyridine 6 was
Table 1. Development of a Catalytic [2 + 2 + 2] Cycloaddition
Based on the above data, we adopted a standard procedure
using degassed THF at 140 °C in a sealed tube without
irradiation. Using these conditions, nitriles 7-18 were
screened to determine the generality of the reaction (Table
2). The electronics of the nitrile did not have a predictable
effect on either conversion or yield. Aromatic (entry 10),
heteroaromatic (entries 1 and 9), benzylic (entry 3), as well
as primary (entry 8) and secondary (entry 12) aliphatic nitriles
were effective reactants. Pyrazine-containing nitrile 15,
nitriles bearing free hydroxyl and amine groups (16 and 17),
and strongly deactivated nitriles (e.g., 18) failed to give
detectable amounts of pyridines. In selected cases where
conversions were low or where products coeluted chromato-
graphically with diyne 1, the desired heterocycles were
obtained with >95% conversion by increasing loading of 2
a Experimental procedures provided in the Supporting Information.
Nitrile: 2-methoxy-5-pyridine carbonitrile. b Solvents were degassed by
bubbling argon for 20 min prior to use. 1,2-DME: dimethoxyethane. 1,2-
DCE: dichloroethane. 1,2-DCB: dichlorobenzene. TCE: trichloroethylene.
DMA: dimethylacetamide. c 1,4-Dioxane, pyridine, and DMA gave <2%
conversion. d Additives at 50 mol %. e Conversions determined by 1H NMR
spectroscopy. f Reaction ran without irradiation.
(9) A reaction of diynes with cyanamides using 2 in 1,4-dioxanes has
been reported: Bon˜aga, L. V. R.; Zhang, H-C.; Maryanoff, B. E. Chem.
Commun. 2004, 21, 2394–2395.
(10) Petit, M.; Chouraqui, G.; Aubert, C.; Malacria, M. Org. Lett. 2003,
5, 2037–2040.
(11) In other intramolecular reactions, the length of the tether affects
the regioselectivity; see: Moretto, A. F.; Zhang, H-C.; Maryanoff, B. E.
J. Am. Chem. Soc. 2001, 123, 3157–3158.
not detected. The regiochemistry of the pyridines was
determined by NoE; data are provided in the Supporting
(12) Examples often append the silyl group externally: (a) McCormick,
M. M.; Duong, H. A.; Zuo, G.; Louie, J. J. Am. Chem. Soc. 2005, 127,
5030–5031. (b) Gutnov, A.; Abaev, V.; Redkin, D.; Fischer, C.; Bonrath,
W.; Heller, B. Synlett 2005, 1188–1190. (c) Varela, J. A.; Castedo, L.; Saa´,
C. J. Org. Chem. 1997, 62, 4189–4192.
(4) (a) Senaiar, R. S.; Young, D. D.; Deiters, A. Chem. Commun. 2006,
1313–1315. (b) Bon˜aga, L. V. R.; Zhang, H-C.; Moretto, A. F.; Ye, H.;
Gauthier, D. A.; Li, J.; Leo, G. C.; Maryanoff, B. E. J. Am. Chem. Soc.
2005, 127, 3473–3485. (c) Groth, U.; Huhn, T.; Kesenheimer, C.;
Kalogerakis, A. Synlett 2005, 1758–1760.
(13) Coordination of pyridines with CpCo is also possible. Examples
of coordination to products of [2 + 2 + 2]-cycloaddition exist. See: Gandon,
V.; Leboeuf, D.; Amslinger, S.; Vollhardt, K. P. C.; Malacria, M.; Aubert,
C. Angew. Chem., Int. Ed. 2005, 44, 7114–7118.
(5) (a) Heller, B.; Oehme, G. Chem. Commun. 1995, 179–180. (b)
Bo¨nnemann, H.; Brinkmann, R.; Schenkluhn, H. Synthesis 1974, 57, 5–
577.
(6) Jonas, K.; Deffense, E.; Habermann, D. Angew. Chem., Int. Ed. 1983,
22, 716–717.
(14) Turek, P.; Nova´k, P.; Pohl, R.; Hocek, M.; Kotora, M. J. Org. Chem.
2006, 71, 8978–8981.
(7) King, R. B.; Treichel, P. M.; Stone, F. G. A. J. Am. Chem. Soc.
1961, 83, 3593–3597.
(15) Saino, N.; Kogure, D.; Okamoto, S. Org. Lett. 2005, 7, 3065–3067.
(16) Nova´k, P.; Pohl, R.; Kotora, M.; Hocek, M. Org. Lett. 2006, 8,
2051–2054.
(8) (a) Gutnov, A.; Heller, B.; Fisher, C.; Drexler, H-J.; Spannenberg,
A.; Sundermann, B.; Sundermann, C. Angew. Chem., Int. Ed. 2004, 43,
3795–3797. (b) Fatland, A. W.; Eaton, B. E. Org. Lett. 2000, 2, 3131–
3133. (c) Bo¨nnemann, H. Angew. Chem., Int. Ed. Engl. 1985, 24, 248–
262.
(17) For a [2 + 2 + 2] example with CO2, see: Louie, J.; Gibby, J. E.;
Farnworth, M. V.; Tekavec, T. N. J. Am. Chem. Soc. 2002, 124, 15188–
15189. (b) Diyne cycloaddition with isocyanates: Yamamoto, Y.; Takagishi,
H.; Itoh, K. Org. Lett. 2001, 3, 2117–2119.
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