CLUSTER
FLP Addition of N-Heterocycles to Unsaturated C–C Bonds
C
tures and that 2e is thermodynamically favored over the
five-membered regioisomer 2e′.
Table 1 Reactivity of Terminal and Internal Alkynylpyridines with
Acknowledgment
The authors gratefully acknowledge financial support from NSERC
of Canada. D.W.S. is grateful for the award of a Canada Research
Chair. L.E.L. is grateful for the award of an NSERC-CGS postgra-
duate scholarship.
B(C6F5)3
B(C6F5)3
R
Me
N
Me
N
Supporting Information for this article is available online at
or
Me
N
r
t
iornat
R
R
B(C6F5)3
B(C6F5)3
References and Notes
Substrate
Product
Yield
(%)
(1) Stephan, D. W.; Erker, G. Angew. Chem. Int. Ed. 2010, 49,
46.
(2) Welch, G. C.; Juan, R. R. S.; Masuda, J. D.; Stephan, D. W.
Science 2006, 314, 1124.
(3) Welch, G. C.; Stephan, D. W. J. Am. Chem. Soc. 2007, 129,
1880.
Me
N
Me
N
>99a
(4) Spies, P.; Erker, G.; Kehr, G.; Bergander, K.; Fröhlich, R.;
Grimme, S.; Stephan, D. W. Chem. Commun. 2007, 5072.
(5) Huber, D. P.; Kehr, G.; Bergander, K.; Fröhlich, R.; Erker,
G.; Tanino, S.; Ohki, Y.; Tatsumi, K. Organometallics 2008,
27, 5279.
B(C6F5)3
1d
2d
(6) Piers, W. E.; Marwitz, A. J. V.; Mercier, L. G. Inorg. Chem.
2011, 50, 12252.
(7) Mömming, C. M.; Otten, E.; Kehr, G.; Fröhlich, R.;
Grimme, S.; Stephan, D. W.; Erker, G. Angew. Chem. Int.
Ed. 2009, 48, 6643.
(8) Dobrovetsky, R.; Stephan, D. W. J. Am. Chem. Soc. 2013,
135, 4974.
(9) Otten, E.; Neu, R. C.; Stephan, D. W. J. Am. Chem. Soc.
2009, 131, 9918.
(10) McCahill, J. S. J.; Welch, G. C.; Stephan, D. W. Angew.
Chem. Int. Ed. 2007, 46, 4968.
(11) Sortais, J.-B.; Voss, T.; Kehr, G.; Fröhlich, R.; Erker, G.
Chem. Commun. 2009, 7417.
(12) Mömming, C. M.; Kehr, G.; Fröhlich, R.; Erker, G. Chem.
Commun. 2011, 47, 2006.
(13) Mömming, C. M.; Frömel, S.; Kehr, G.; Fröhlich, R.;
Grimme, S.; Erker, G. J. Am. Chem. Soc. 2009, 131, 12280.
(14) Dureen, M. A.; Stephan, D. W. J. Am. Chem. Soc. 2009, 131,
8396.
Me
N
Me
N
Me
1e
Me
1f
N
2e
95b
B(C6F5)3
B(C6F5)3
2e′
2e
Me
N
N
97a
B(C6F5)3
2f
a Reaction conditions: r.t., 13 h.
b Reaction conditions: 115 °C, 13 h.
In a similar situation, the enyne 1f cleanly forms six-mem-
bered zwitterion 2f (Table 1) at ambient temperature and
was isolated in 97% yield. This product was also charac-
terized crystallographically (Figure 2).
(15) Dureen, M. A.; Brown, C. C.; Stephan, D. W.
Organometallics 2010, 29, 6594.
(16) Dureen, M. A.; Brown, C. C.; Stephan, D. W.
Organometallics 2010, 29, 6422.
(17) Mömming, C. M.; Kehr, G.; Wibbeling, B.; Fröhlich, R.;
Schirmer, B.; Grimme, S.; Erker, G. Angew. Chem. Int. Ed.
2010, 49, 2414.
(18) Voss, T.; Chen, C.; Kehr, G.; Nauha, E.; Erker, G.; Stephan,
D. W. Chem. Eur. J. 2010, 16, 3005.
(19) Mahdi, T.; Heiden, Z. M.; Grimme, S.; Stephan, D. W.
J. Am. Chem. Soc. 2012, 134, 4088.
(20) Mahdi, T.; del Castillo, J. N.; Stephan, D. W.
Organometallics 2013, 32, 1971.
(21) Spande, T. F.; Jain, P.; Garraffo, H. M.; Pannell, L. K.; Yeh,
H. J. C.; Daly, J. W.; Fukumoto, S.; Imamura, K.;
Tokuyama, T.; Torres, J. A.; Snelling, R. R.; Jones, T. H.
J. Nat. Prod. 1999, 62, 5.
(22) Daly, J. W.; Spande, T. F.; Garraffo, H. M. J. Nat. Prod.
2005, 68, 1556.
In conclusion we have demonstrated that alkyne- and al-
kene-tethered pyridines and quinolines undergo cycliza-
tion upon addition of one equivalent of B(C6F5)3. If the N-
heterocycle is not sufficiently sterically encumbered, a
conventional Lewis adduct will result, precluding cycliza-
tion. The reversible nature of these activations are indicat-
ed in the reactions of 2b with H2 generating the
pyridinium hydridoborate salt 3b and by the isomerization
of regioisomers 2e and 2e′. It is also interesting to note
that the formation of 2e and 2f are, to the best of our
knowledge, the first examples of N–B FLP additions to in-
ternal alkynes. We are continuing to explore the applica-
tions of frustrated Lewis pair activation in target-oriented
synthesis.
(23) Representative Procedure for Cyclizations – Synthesis of
2c from 1b
In a nitrogen-filled glovebox, alkene 1b (16 mg, 0.1 mmol)
was dissolved in toluene (1 mL) and transferred to a vial
© Georg Thieme Verlag Stuttgart · New York
Synlett 2014, 25, A–D