Zirconocene-mediated intermolecular coupling of one molecule of Si-tethered Diyne with three molecules of organonitriles: One-pot formation of pyrrolo[3,2-c]pyridine derivatives via cleavage of C≡n triple bonds of organonitriles

Article abstract of DOI:10.1021/ja0497173

One Si-tethered diyne is coupled in one pot with three molecules of organonitriles promoted by a low-valent zirconocene species. Cleavage of one of the three C≡N triple bonds and cleavage of the two Si-C bonds take place to afford pyrrolo[3,2-c]pyridine derivatives after hydrolysis. Copyright

Full text of DOI:10.1021/ja0497173

Published on Web 05/19/2004
Zirconocene-Mediated Intermolecular Coupling of One Molecule of
Si-Tethered Diyne with Three Molecules of Organonitriles: One-Pot
Formation of Pyrrolo[3,2-c]pyridine Derivatives via Cleavage of CtN Triple
Bonds of Organonitriles
Xiaohua Sun,† Congyang Wang,‡ Zhiping Li,‡ Shiwei Zhang,‡ and Zhenfeng Xi*,‡
Institute of Chemistry, Chinese Academy of Sciences, Beijing 100080, China, and Key Laboratory of Bioorganic
Chemistry and Molecular Engineering of Ministry of Education, College of Chemistry, Peking UniVersity,
Beijing 100871 China
Received January 16, 2004; E-mail: zfxi@pku.edu.cn
Table 1. Zirconocene-Mediated Coupling of a Bis(alkynyl)silane
with Three Molecules of Organonitriles Affording
Pyrrolo[3,2-c]pyridine Derivatives
Transition-metal-mediated reaction of organonitriles has attracted
much attention, since novel reaction patterns of the CtN triple
bonds can be developed and synthetically useful methodologies for
construction of C-C, C-N, and C-O bonds can be expected.1
Particularly, transition-metal-mediated coupling of organonitriles
with other unsaturated organic substrates such as alkynes is of great
synthetic interest.2-5 In this paper, we report a zirconocene-mediated
coupling reaction of organonitriles with alkynes, in which one Si-
tethered diyne 1 is coupled in one pot with three molecules of
nitriles promoted by a low-valent zirconocene species (eq 1). Along
with coupling, cleavage of one of the three CtN triple bonds and
cleavage of the two Si-C bonds took place, affording pyrrolo[3,2-
c]pyridine derivatives 2 after hydrolysis.6
A typical procedure is as follows. To a toluene solution (10 mL)
of Cp2ZrBu2 (Negishi reagent), generated in situ from the reaction
of 1 mmol of Cp2ZrCl2 and 2 mmol of n-BuLi at - 78 °C, was
added 1 mmol of bis(phenylethynyl)dimethylsilane (1a, Ar ) Ph).7
The reaction mixture was warmed to 50 °C and stirred at this
temperature for 3 h. A zirconacyclobutene-silacyclobutene fused
ring compound (3a, Ar ) Ph) as a reactive organometallic
intermediate was formed (eq 2), as previously reported by Takahashi
and co-workers.7 Benzonitrile (3.5 mmol) was then added and the
reaction mixture was stirred at 50 °C for 1 h. The reaction mixture
was then cooled to room temperature and quenched with saturated
aqueous NaHCO3. Normal workup procedure afforded the fused-
ring compound 2a (Ar ) R1 ) Ph) in 70% isolated yield.
a Isolated yields. Reaction conditions are given in eq 2.
2-thiophenyl) have been determined by single-crystal X-ray analysis
(see Supporting Information).
Listed in Table 1 are representative results obtained from the
zirconocene-mediated coupling of bis(alkynyl)silanes and organo-
nitriles. Both aliphatic and aromatic nitriles could be used to afford
the final products in high isolated yields. The structures of
compounds 2b (Ar ) Ph, R1 ) tolyl) and 2c (Ar ) Ph, R1 )
When a 1:1 molar ratio mixture of p-tolunitrile and 2-thiophen-
ecarbonitrile was treated with 3a (eq 3), compound 2h was obtained
† Institute of Chemistry, CAS.
‡ Peking University.
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C O M M U N I C A T I O N S
as one of the products and has been structurally characterized by
single-crystal X-ray analysis (see Supporting Information). This
result indicates that three molecules of nitriles are incorporated into
the product via a step-by-step manner.
(Scheme 1, c), product 2k containing a CD2 moiety was obtained.
Addition of p-tolunitrile as a third molecule of nitrile to the reaction
intermediate of 3a with two molecules of i-PrCN afforded product
2l in 67% isolated yield (Scheme 1, d). This product 2l was formed
chemo- and regioselectively from two molecules of i-PrCN and
one molecule of p-tolunitrile. These results are instructive for
understanding the reaction mechanism (see Supporting Information
for a proposed reaction mechanism). Further investigation to
elucidate the reaction mechanisms and further applications of these
novel and synthetically useful reactions are in progress.
Acknowledgment. This work was partially supported by the
Natural Science Foundation of China (29825105, 20172003,
20232010) and the Major State Basic Research Development
Program (G2000077502-D). Cheung Kong Scholars Program and
Qiu Shi Science & Technologies Foundation are gratefully ac-
knowledged.
Supporting Information Available: Experimental details, char-
Addition of PrCN to a 1:1 molar ratio mixture of 3a and 3b (Ar
) tolyl) afforded two products 2d and 2g in 72% (1:1) combined
isolated yield (eq 4). No cross-coupled products were obtained,
indicating that the coupling reaction and cleavage proceeded
intramolecularly.
1
acterization data, copies of H and 13C NMR spectra for all isolated
compounds and crystallographic data, positional and thermal parameters,
and lists of bond lengths and angles for 2b, 2c, 2h, 2j. This material is
available free of charge via the Internet at http//pubs.acs.org.
References
(1) For leading recent reviews, see: (a) Kukushkin, V.; Y.; Pombeiro, A. J.
L. Chem. ReV. 2002, 102, 1771-1802 and references therein. (b)
Murahashi, S. I.; Takaya, H. Acc. Chem. Res. 2000, 33, 225-233. (c)
Michelin, R. A.; Mozzon, M.; Bertani, R. Coord. Chem. ReV. 1996, 147,
299-338 and references therein.
(2) For reviews on metal-mediated cycloadditions of alkynes and nitriles
forming pyridine derivatives, see: (a) Varela, J. A.; Saa, C. Chem. ReV.
2003, 103, 3787-3801. (b) Bonnemann, H. Angew. Chem., Int. Ed. Engl.
1985, 24, 248-262. (c) Vollhardt, K. P. C. Angew. Chem., Int. Ed. Engl.
1984, 23, 539-556.
(3) For formation of azazirconacyclopentadienes, see: (a) Takahashi, T.; Xi,
C. J.; Xi, Z. F.; Kageyama, M.; Fischer, R.; Nakajima, K.; Negishi, E. J.
Org. Chem. 1998, 63, 6802-6808. (b) Negishi, E.; Holms, S. J.; Tour, J.
M.; Miller, J. A.; Cederbaum, F. E.; Swanson, D. R.; Takahashi, T. J.
Am. Chem. Soc. 1989, 111, 3336-3346. (c) Fagan, P. J.; Nugent, W. A.
J. Am. Chem. Soc. 1988, 110, 2310-2312. (d) Quntar, A. A.; Melman,
A.; Srebnik, M. J. Org. Chem. 2002, 67, 3769-3772. See also: (e)
Buchwald, S. L.; King, S. M. J. Am. Chem. Soc. 1991, 113, 258-
265.
Interestingly, when i-PrCN was used, the reaction could be
stopped after a second nitrile was incorporated into the reaction
intermediate. As demonstrated in Scheme 1, the ketone derivative
2j (Scheme 1, b) was obtained in 51% isolated yield and its structure
was determined by single-crystal X-ray analysis (see Supporting
Information). When the reaction mixture was quenched with D2O
Scheme 1
(4) Fpr formation of aldimido-zirconocene complexes, see: (a) Doring, S.;
Erker, G.; Frohlich, R. J. Organomet. Chem. 2002, 643, 61-67. (b)
Maraval, A.; Donnadieu, B.; Igau, A.; Majoral, J. P. Organometallics 1999,
18, 3138-3141. (c) Breen, T. L.; Stephan, D. W. Organometallics 1997,
16, 365-369. (d) Zippel, T.; Arndt, P.; Ohff, A.; Kempe, R.; Rosenthal,
U. Organometallics 1998, 17, 4429-4437. (e) Ohff, A.; Zippel, T.; Arndt,
P.; Spannenberg, A.; Kempe, R.; Rosenthal, U. Organometallics 1998,
17, 1649-1651.
(5) For formation of zirconocene-imido complexes and reactions, see: (a)
Walsh, P. J.; Hollander, F. J.; Bergman, R. G. J. Am. Chem. Soc. 1988,
110, 8729-8731. (b) Walsh, P. J.; Hollander, F. J.; Bergman, R. G.
Organometallics 1993, 12, 3705-3723. (c) Sweeney, Z. K.; Salsman, J.
L.; Andersen, R. A.; Bergman, R. G. Angew. Chem., Int. Ed. 2000, 39,
2339-2343. (d) Blum, S. A.; Tan, K. L.; Bergman, R. G. J. Org. Chem.
2003, 68, 4127-4137.
(6) For metal-mediated cleavage of CtN triple bonds of organonitriles, see
the following. Mo: (a) Tanabe, Y.; Seino, H.; Ishii, Y.; Hidai, M. J. Am.
Chem. Soc. 2000, 122, 1690-1699. (b) Seino, H.; Tanabe, Y.; Ishii, Y.;
Hidai, M. Inorg. Chim. Acta 1998, 280, 163-171. W: (c) Schrock, R.
R.; Listemann, M. L.; Sturgeoff, L. G. J. Am. Chem. Soc. 1982, 104,
4291-4293. (d) Chisholm, M. H.; Folting, K.; Tiedtke, D. B.; Lemoigno,
F.; Eisenstein, O. Angew. Chem., Int. Ed. Engl. 1995, 34, 110-112. (e)
Chisholm, M. H.; Folting, K.; Lynn, M. L.; Tiedtke, D. B.; Lemoigno,
F.; Eisentein, O. Chem. Eur. J. 1999, 5, 2318-2326. Ti: (f) Xi, Z.; Sato,
K.; Gao, Y.; Lu, J.; Takahashi, T. J. Am. Chem. Soc. 2003, 125, 9568-
9569. (g) Doxsee, K. M.; Mouser, J. K. M. Organometallics 1990, 9,
3012-3014.
(7) (a) Xi, Z.; Fischer, R.; Hara, R.; Sun, W.; Obora, Y.; Suzuki, N.; Nakajima,
K.; Takahashi, T. J. Am. Chem. Soc. 1997, 119, 12842-12848. (b)
Takahashi, T.; Xi, Z.; Obora, Y.; Suzuki, N. J. Am. Chem. Soc. 1995,
117, 2665-2666. (c) Yu, T.; Deng, L.; Zhao, C.; Li, Z.; Xi, Z. Tetrahedron
Lett. 2003, 44, 677-679.
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