Page 5 of 7
Journal of the American Chemical Society
Zürcher, S.; Tilley, T. D., “New Zirconocene-Coupling Route to Large,
Functionalized Macrocycles.” J. Am. Chem. Soc. 2000, 122, 10345-10352;
c) Nugent, W. A.; Thorn, D. L.; Harlow, R. L., “Cyclization of diacetylenes
to E,E exocyclic dienes. Complementary procedures based on titanium and
zirconium reagents.” J. Am. Chem. Soc. 1987, 109, 2788-2796; (d) Wielstra,
Y.; Gambarotta, S.; Meetsma, A.; De Boer, J. L.; Chiang, M. Y., “Carbon-
carbon bond formation versus hydrogen transfer in the reaction of alkynes
with mono(cyclopentadienyl)zirconium(II) complexes: regioselective
dimerization, cocyclotrimerization, and catalytic cyclotrimerization. The
preparation and x-ray structures of Cp(dmpe)XZr[(R)C:C(R')C(R):C(R')]
and Related Alkaloids.” Chem. Rev. 2009, 109, 3080-3098; (e) Undheim,
K.; Benneche, T., 6.02 - Pyrimidines and their Benzo Derivatives A2 -
Katritzky, Alan R. In Comprehensive Heterocyclic Chemistry II, Rees, C.
W.; Scriven, E. F. V., Eds. Pergamon: Oxford, 1996; pp 93-231.
1
2
3
4
5
6
7
8
9
(
(17) (a) Perreault, S.; Rovis, T., “Multi-component cycloaddition
approaches in the catalytic asymmetric synthesis of alkaloid targets.” Chem.
Soc. Rev. 2009, 38, 3149-3159; (b) Gulevich, A. V.; Dudnik, A. S.;
Chernyak, N.; Gevorgyan, V., “Transition Metal-Mediated Synthesis of
Monocyclic Aromatic Heterocycles.” Chem. Rev. 2013, 113, 3084-3213;
(c) Chopade, P. R.; Louie, J., “[2+2+2] Cycloaddition Reactions Catalyzed
by Transition Metal Complexes.” Adv. Synth. Catal. 2006, 348, 2307-2327.
(18) (a) Hill, M. D.; Movassaghi, M., “New Strategies for the Synthesis
of Pyrimidine Derivatives.” Chem. Eur. J. 2008, 14, 6836-6844; (b)
Mahfoudh, M.; Abderrahim, R.; Leclerc, E.; Campagne, J.-M., “Recent
Approaches to the Synthesis of Pyrimidine Derivatives.” Eur. J. Org. Chem.
2017, 2017, 2856-2865; (c) Karad Somnath, N.; Liu, R. S.,
“Regiocontrolled Gold‐Catalyzed [2+2+2] Cycloadditions of Ynamides
with Two Discrete Nitriles to Construct 4‐Aminopyrimidine Cores.”
Angew. Chem. Int. Ed. 2014, 53, 9072-9076; (d) You, X.; Yu, S.; Liu, Y.,
“Reactions of Zirconocene Butadiyne or Monoyne Complexes with
Nitriles: Straightfoward Synthesis of Functionalized Pyrimidines.”
Organometallics 2013, 32, 5273-5276; (e) Chen, P.; Song, C.-x.; Wang,
W.-s.; Yu, X.-l.; Tang, Y., “TfOH-mediated [2 + 2 + 2] cycloadditions of
ynamides with two discrete nitriles: synthesis of 4-aminopyrimidine
derivatives.” RSC Advances 2016, 6, 80055-80058; (f) Burlakov, V. V.;
Becker, L.; Bogdanov, V. S.; Andreev, M. V.; Arndt, P.; Spannenberg, A.;
[
R = CH3; R' = H, CH3; X = Cl, CH3; dmpe = 1,2-
bis(dimethylphosphino)ethane] and of CpZr(dmpe)Cl[C.tplbond.C(t-
Bu)][CH:CH(t-Bu)].” Organometallics 1989, 8, 2696-2702.
(10) (a) Schaefer, C.; Werz, D. B.; Staeb, T. H.; Gleiter, R.; Rominger,
F., “CpCo-Stabilized Cyclopentadienones from Cyclobutadiene
1
1
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1
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0
Complexes:ꢀ
Experimental
and
Theoretical
Investigations.”
Organometallics 2005, 24, 2106-2113; (b) Schore, N. E., “Transition metal-
mediated cycloaddition reactions of alkynes in organic synthesis.” Chem.
Rev. 1988, 88, 1081-1119; (c) Gleiter, R.; Werz, D. B., “Reactions of Metal-
Complexed Carbocyclic 4π Systems.” Organometallics 2005, 24, 4316-
4
329; (d) Shibata, T.; Yamashita, K.; Ishida, H.; Takagi, K., “Iridium
Complex Catalyzed Carbonylative Alkyne−Alkyne Coupling for the
Synthesis of Cyclopentadienones.” Org. Lett. 2001, 3, 1217-1219.
(11) (a) Sikora, D. J.; Rausch, M. D., “Reactions of Cp2M(CO)2 and
Cp2M(CO)(PPh3) (M = Zr, Hf) with acetylenes: Formation of some
metallacyclopentadiene complexes of zirconocene and hafnocene.” J.
Organomet. Chem. 1984, 276, 21-37; (b) Guram, A. S.; Guo, Z.; Jordan, R.
F., “Zirconium-mediated reactions of carbon monoxide and alkynes.
Insertion chemistry of cationic Zr(IV) .eta.2-acyl and alkenyl complexes.”
J. Am. Chem. Soc. 1993, 115, 4902-4903; (c) Takahashi, T.; Huo, S.; Hara,
R.; Noguchi, Y.; Nakajima, K.; Sun, W.-H., “Reaction of
Zirconacyclopentadienes with CO in the Presence of n-BuLi. Selective
Formation of Cyclopentenone Derivatives from Two Alkynes and CO.” J.
Am. Chem. Soc. 1999, 121, 1094-1095; (d) Li, H.; Liu, L.; Zhao, F.; Wang,
C.; Wang, C.; Song, Q.; Zhang, W.-X.; Xi, Z., “Carbonylation of 1-
Lithiobutadiene with Carbon Monoxide Followed by Intramolecular
Acyllithiation of C═C Double Bond and Intermolecular Acylation with
Acid Chloride: Scope, Applications, and Mechanistic Aspects.” J. Org.
Chem. 2012, 77, 4793-4800.
Baumann, W.; Rosenthal, U., “Reactivity of
a Seven‐Membered
Zirconacyclocumulene towards CN Multiple Bonds – Formation of
Metallaheterocycles by Insertion of C≡N and C=N Groups.” Eur. J. Inorg.
Chem. 2014, 2014, 5304-5310; (g) Fuji, M.; Obora, Y., “FeCl3-Assisted
Niobium-Catalyzed Cycloaddition of Nitriles and Alkynes: Synthesis of
Alkyl- and Arylpyrimidines Based on Independent Functions of NbCl5 and
FeCl3 Lewis Acids.” Org. Lett. 2017, 19, 5569-5572; (h) Satoh, Y.; Yasuda,
K.; Obora, Y., “Strategy for the Synthesis of Pyrimidine Derivatives:
NbCl5-Mediated Cycloaddition of Alkynes and Nitriles.” Organometallics
2012, 31, 5235-5238; (i) Xie, L.-G.; Niyomchon, S.; Mota, A. J.; González,
L.; Maulide, N., “Metal-free intermolecular formal cycloadditions enable
an orthogonal access to nitrogen heterocycles.” Nat. Commun. 2016, 7,
10914; (j) Lane, T. K.; Nguyen, M. H.; D'Souza, B. R.; Spahn, N. A.; Louie,
J., “The iron-catalyzed construction of 2-aminopyrimidines from
alkynenitriles and cyanamides.” Chem. Commun. 2013, 49, 7735-7737.
(19) Liu, Y.; Yan, X.; Yang, N.; Xi, C., “Highly regioselective
cyclotrimerization of terminal alkynes catalyzed by Fe(II) complexes
(12) Gilbert, Z. W.; Hue, R. J.; Tonks, I. A., “Catalytic formal [2+2+1]
synthesis of pyrroles from alkynes and diazenes via TiII/TiIV redox
catalysis.” Nature Chemistry 2015, 8, 63.
(13) (a) Denhez, C.; Médégan, S.; Hélion, F.; Namy, J.-L.; Vasse, J.-L.;
Szymoniak, J., “Reduction of Cp2ZrCl2 with Mischmetall:ꢀ A New Method
for Generating an Efficient “Cp2Zr” Equivalent.” Org. Lett. 2006, 8, 2945-
bearing
2-(benzimidazolyl)-6-(1-(arylimino)ethyl)pyridines.”
Catal.
Commun. 2011, 12, 489-492.
2
947; (b) Zirngast, M.; Marschner, C.; Baumgartner, J., “Group 4
(20) (a) Hilt, G.; Vogler, T.; Hess, W.; Galbiati, F., “A simple cobalt
catalyst system for the efficient and regioselective cyclotrimerisation of
alkynes.” Chem. Commun. 2005, 1474-1475; (b) Hsieh, J.-C.; Cheng, C.-
H., “O-Dihaloarenes as aryne precursors for nickel-catalyzed [2 + 2 + 2]
cycloaddition with alkynes and nitriles.” Chem. Commun. 2008, 2992-2994.
(21) Takahashi, T.; Tsai, F.-Y.; Kotora, M., “Selective Formation of
Substituted Pyridines from Two Different Alkynes and a Nitrile:ꢀ Novel
Coupling Reaction of Azazirconacyclopentadienes with Alkynes.” J. Am.
Chem. Soc. 2000, 122, 4994-4995.
(22) Takahashi, T.; Tsai, F.-Y.; Li, Y.; Wang, H.; Kondo, Y.; Yamanaka,
M.; Nakajima, K.; Kotora, M., “Selective Preparation of Pyridines,
Pyridones, and Iminopyridines from Two Different Alkynes via
Azazirconacycles.” J. Am. Chem. Soc. 2002, 124, 5059-5067.
(23) (a) Hill, J. E.; Balaich, G.; Fanwick, P. E.; Rothwell, I. P., “The
chemistry of titanacyclopentadiene rings supported by 2,6-
diphenylphenoxide ligation: stoichiometric and catalytic reactivity.”
Organometallics 1993, 12, 2911-2924; (b) Tanaka, R.; Yuza, A.; Watai, Y.;
Suzuki, D.; Takayama, Y.; Sato, F.; Urabe, H., “One-Pot Synthesis of
Metalated Pyridines from Two Acetylenes, a Nitrile, and a Titanium(II)
Alkoxide.” J. Am. Chem. Soc. 2005, 127, 7774-7780; (c) Varela, J. A.; Saá,
C., “Construction of Pyridine Rings by Metal-Mediated [2ꢀ+ꢀ2ꢀ+ꢀ2]
Cycloaddition.” Chem. Rev. 2003, 103, 3787-3802.
Metallocene Complexes of Tris(trimethylsilyl)silylacetylene and Related
Alkynes.” Organometallics 2008, 27, 2570-2583; (c) Shenyong, R.;
Takashi, S.; David, N.; Hiroyuki, S.; Kiyohiko, N.; Ken-ichiro, K.; Zhiying,
S.; Tamotsu, T., “Selective Dimerization of Aryl-substituted Terminal
Alkynes on Bis(indenyl)zirconocene Derivatives.” Chem. Lett. 2011, 40,
1
443-1444; (d) Bousrez, G.; Jaroschik, F.; Martinez, A.; Harakat, D.;
Nicolas, E.; Le Goff, X. F.; Szymoniak, J., “Reactivity differences between
,4- and 2,5-disubstituted zirconacyclopentadienes: a highly selective and
general approach to 2,4-disubstituted phospholes.” Dalton Trans. 2013, 42,
2
1
0997-11004.
(14) Ma, W.; Yu, C.; Chen, T.; Xu, L.; Zhang, W.-X.; Xi, Z.,
“
Metallacyclopentadienes: synthesis, structure and reactivity.” Chem. Soc.
Rev. 2017, 46, 1160-1192.
15) Although alkyne homotrimerization products were not produced
(
when 3b was treated with excess phenylacetylene, in the presence of certain
additives (nitriles, CO), their formation was observed.
(16) (a) Gómez-de la Torre, F.; de la Hoz, A.; Jalón, F. A.; Manzano, B.
R.; Rodríguez, A. M.; Elguero, J.; Martínez-Ripoll, M., “Pd(II) Complexes
with Polydentate Nitrogen Ligands. Molecular Recognition and Dynamic
Behavior Involving Pd−N Bond Rupture. X-ray Molecular Structures of
[
[
{Pd(C6HF4)2}(bpzpm)] and [{Pd(η3-C4H7)}2(bpzpm)] (CF3SO3)2
bpzpm = 4,6-Bis(pyrazol-1-yl)pyrimidine].” Inorg. Chem. 2000, 39, 1152-
(24) A new species was formed upon addition of nitrile (2 equiv.) to 2,
with displacement of THF. Potential assignments include a bis(nitrile) ad-
duct or a diazazirconacyclopentadiene complex.
(25) (a) Becker, L.; Arndt, P.; Jiao, H.; Spannenberg, A.; Rosenthal, U.,
“Nitrile–Nitrile C� C Coupling at Group 4 Metallocenes to Form 1-
Metalla-2,5-diaza-cyclopenta-2,4-dienes: Synthesis and Reactivity.”
Angew. Chem. Int. Ed. 2013, 52, 11396-11400; (b) Becker, L.; Strehler, F.;
Korb, M.; Arndt, P.; Spannenberg, A.; Baumann, W.; Lang, H.; Rosenthal,
1
162; (b) Kua, J.; Xu, X.; Periana, R. A.; Goddard, W. A., “Stability and
Thermodynamics of the PtCl2 Type Catalyst for Activating Methane to
Methanol:ꢀ A Computational Study.” Organometallics 2002, 21, 511-525;
(c) Warsink, S.; Chang, I. H.; Weigand, J. J.; Hauwert, P.; Chen, J.-T.;
Elsevier, C. J., “NHC Ligands with a Secondary Pyrimidyl Donor for
Electron-Rich Palladium(0) Complexes.” Organometallics 2010, 29, 4555-
4
561; (d) Walker, S. R.; Carter, E. J.; Huff, B. C.; Morris, J. C., “Variolins
ACS Paragon Plus Environment