Organic Letters
Letter
2009, 14, 1058−1066. (e) Bull, J. A.; Mousseau, J. J.; Pelletier, G.;
Charette, A. B. Chem. Rev. 2012, 112, 2642−2713.
unobserved intermediate III. Coordination of pyridine to III
regenerates the intermediate complex 5 to close the catalytic
cycle. Catalytically active intermediate 5 persisted in the reaction
mixture throughout the catalysis as oberved by 1H and 31P NMR
analyses.
(5) (a) Birch, A. J.; Karakhamor, E. A. J. Chem. Soc., Chem. Commun.
1975, 480−481. (b) Olah, G. A.; Hunadi, R. J. J. Org. Chem. 1981, 46,
715−718. (c) Donohoe, T. J.; McRiner, A. J.; Sheldrake, P. Org. Lett.
2000, 2, 3861−3863. (d) Danishefsky, S.; Cavanaugh, R. J. Am. Chem.
Soc. 1968, 90, 520−521. (e) Danishefsky, S.; Cain, P.; Nagel, A. J. Am.
Chem. Soc. 1975, 97, 380−387. (f) Danishefsky, S.; Cain, P. J. Org. Chem.
1975, 40, 3606−3608. (g) Danishefsky, S.; Cain, P. J. Steroid Biochem.
1975, 6, 177−181.
In summary, efficient regioselective 1,4-hydroboration of
pyridine compounds was demonstrated using well-defined
transition metal catalysts. Stoichiometric experiments and in
situ spectral studies allowed identification of the reaction
intermediates 2−5. Intermediates 2 and 3 are independently
synthesized, characterized, and further used in catalysis.
Phosphine ligated complex 3 turned out to be the optimal
catalyst for the regioselective 1,4-hydroboration of pyridines.
Solvent is required only when the substrate is solid or the
reaction mixture turns inhomogeneous; otherwise catalysis
proceeded very well under solventless conditions. Supported
by the experimental observations, a mechanism is postulated
involving in situ generation of mononuclear Ru−H complex 5,
which undergoes an intramolecular 1,5-hydride transfer leading
to the regioselective 1,4-hydroboration of pyridines. Further
studies to elucidate the scope of this transformation and the
details of the regiochemical discrimination are currently
underway.
(6) (a) Comins, D.; Abdullah, A. H. J. Org. Chem. 1984, 49, 3392−
3394. (b) Sundberg, R. J.; Hamilton, G.; Trindle, C. J. Org. Chem. 1986,
51, 3672−367.
(7) Katritzky, A. R.; Taylor, R. Adv. Heterocycl. Chem. 1990, 47, 1−467.
(8) (a) Adkins, H.; Kuick, L. F.; Farlow, M.; Wojcik, B. J. Am. Chem.
Soc. 1934, 56, 2425−2428. (b) Freifelder, M.; Stone, G. R. J. Org. Chem.
1961, 26, 3805−3808. (c) Lunn, G.; Sansone, E. B. J. Org. Chem. 1986,
51, 513−517. (d) Takasaki, M.; Motoyama, Y.; Higashi, K.; Yoon, S.-H.;
Mochida, I.; Nagashima, H. Chem. - Asian J. 2007, 2, 1524−1533.
(e) Buil, M. L.; Esteruelas, M. A.; Niembro, S.; Olivan, M.; Orzechowski,
L.; Pelayo, C.; Vallribera, A. Organometallics 2010, 29, 4375−4383.
(f) Freifelder, M. Practical Catalytic Hydrogenation; Wiley Interscience:
1971. (g) Glorius, F. Org. Biomol. Chem. 2005, 3, 4171−4175.
(9) (a) Hao, L.; Harrod, J. F.; Lebuis, A.-M.; Mu, Y.; Shu, R.; Samuel,
E.; Woo, H.-G. Angew. Chem., Int. Ed. 1998, 37, 3126−3129. (b) Harrod,
J. F.; Shu, R.; Woo, H. G.; Samuel, E. Can. J. Chem. 2001, 79, 1075−
1085. (c) Gutsulyak, D. V.; van der Est, A.; Nikonov, G. I. Angew. Chem.,
ASSOCIATED CONTENT
* Supporting Information
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Int. Ed. 2011, 50, 1384−1387. (d) Konigs, C. D. F.; Klare, H. F. T.;
̈
S
Ostreich, M. Angew. Chem., Int. Ed. 2013, 52, 10076−10079.
(10) Oshima, K.; Ohmura, T.; Suginome, M. J. Am. Chem. Soc. 2011,
133, 7324−7327.
The Supporting Information is available free of charge on the
(11) Daley, E. N.; Vogels, C. M.; Geier, S. J.; Decken, A.; Doherty, S.;
Westcott, S. A. Angew. Chem., Int. Ed. 2015, 54, 2121−2125.
Experimental procedures and spectral data; single-crystal
X-ray data of complex 3 CCDC 1444045 (PDF)
(12) Arrowsmith, M.; Hill, M. S.; Hadlington, T.; Kociok-Kohn, G.
̈
Organometallics 2011, 30, 5556−5559.
(13) Intemann, J.; Lutz, M.; Harder, S. Organometallics 2014, 33,
5722−5729.
AUTHOR INFORMATION
Corresponding Author
■
(14) Intemann, J.; Bauer, H.; Pahl, J.; Maron, L.; Harder, S. Chem. - Eur.
J. 2015, 21, 11452−11461.
Author Contributions
†A.K. and B.C. contributed equally to this work.
Notes
(15) Oshima, K.; Ohmura, T.; Suginome, M. J. Am. Chem. Soc. 2012,
134, 3699−3702.
(16) Dudnik, A. S.; Weidner, V. L.; Motta, A.; Delferro, M.; Marks, T. J.
Nat. Chem. 2014, 6, 1100−1107.
(17) Fan, X.; Zheng, J.; Li, Z. H.; Wang, H. J. Am. Chem. Soc. 2015, 137,
4916−4919.
The authors declare no competing financial interest.
(18) Kaithal, A.; Chatterjee, B.; Gunanathan, C. Org. Lett. 2015, 17,
4790−4793.
ACKNOWLEDGMENTS
■
We thank SERB New Delhi (SR/S1/OC-16/2012 and SR/S2/
RJN-64/2010), DAE and NISER for financial support. C.G.
thanks Prof. Bhargava B. L., NISER for his kind help. A.K. and
B.C. thank DST and UGC for the fellowships. C.G. is a
Ramanujan Fellow.
(19) Bennett, M. A.; Smith, A. K. J. Chem. Soc., Dalton Trans. 1974,
233−241.
(21) Chatterjee, B.; Gunanathan, C. Chem. Commun. 2014, 50, 888−
890.
(22) First-order kinetics is observed for the regioselective 1,4-
hydroboration of pyridine using catalyst 3. See Figure S2.
(23) No hydride signal at δ −10.2 ppm that corresponds to complex 6
was observed. See refs 18 and 21.
REFERENCES
■
(1) (a) Cozzi, P.; Carganico, G.; Fusar, D.; Grossoni, M.;
Menichincheri, M.; Pinciroli, V.; Tonani, R.; Vaghi, F.; Salvati, P. J.
Med. Chem. 1993, 36, 2964−2972. (b) Kumar, P. P.; Stotz, S. C.;
Paramashivappa, R.; Beedle, A. M.; Zamponi, G. W.; Rao, A. S. Mol.
(24) 1H NMR kinetic experiments at 50 °C indicated that the rate law
is first order with [3], [HBpin], and [Py]. However, at a higher
concentration (0.8 to 1 equiv) of pyridine, the rate approached being
zero order. See ref 20.
́
Pharmacol. 2002, 61, 649−658. (c) Lopez-Arrieta, J. M.; Birks, J.
Cochrane Database Syst. Rev. 2002, 3, CD000147. (d) Lavilla, R. J. Chem.
Soc., Perkin Trans. 1 2002, 1141−1156.
(2) Pollak, N.; Dolle, C.; Ziegler, M. Biochem. J. 2007, 402, 205−218.
̈
(3) Ouellet, S. G.; Walji, A. M.; MacMillan, D. W. C. Acc. Chem. Res.
2007, 40, 1327−1339.
(4) (a) Eisner, U.; Kuthan, J. Chem. Rev. 1972, 72, 1−42. (b) Stout, D.
M.; Meyers, A. I. Chem. Rev. 1982, 82, 223−243. (c) Keay, J. G. In
Comprehensive Organic Synthesis; Trost, B. M., Fleming, I., Eds.;
Pergamon: 1991; Vol. 8, Chapter 3.6, pp 579−602. (d) Edraki, N.;
Mehdipour, A. R.; Khoshneviszadeh, M.; Miri, R. Drug Discovery Today
D
Org. Lett. XXXX, XXX, XXX−XXX