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Table 2 Evaluation of different N-substituents
Notes and references
1 J. A. Joule and K. Mills, Heterocycl. Chem., Wiley, New York, 5th edn,
2010.
2 For reviews on C–H functionalization, see: (a) T. W. Lyons and M. S.
Sanford, Chem. Rev., 2010, 110, 1147; (b) L. Ackermann, Chem. Rev.,
2011, 111, 1315; (c) K. M. Engle, T.-S. Mei, M. Wasa and J.-Q. Yu,
Acc. Chem. Res., 2012, 45, 788; (d) D. Y.-K. Chen and S. W. Youn,
Chem. – Eur. J., 2012, 18, 9452; (e) J. Wencel-Delord and F. Glorius,
Nat. Chem., 2013, 5, 369.
3 For heteroarene C–H functionalization: (a) S. H. Cho, J. Y. Kim,
J. Kwak and S. Chang, Chem. Soc. Rev., 2011, 40, 5068; (b) F. Collet,
R. H. Dodd and P. Dauban, Chem. Commun., 2009, 5061; (c) V. S.
Thirunavukkarasu, S. I. Kozhushkov and L. Ackermann, Chem.
Commun., 2014, 50, 29.
4 For pyridine C–H functionalization: (a) Y. Nakao, Synthesis, 2011, 3209.
For an elegant C3-selective oxidative C–H olefination: (b) M. Ye,
G.-L. Gao and J.-Q. Yu, J. Am. Chem. Soc., 2011, 133, 6964.
5 For directed alkenylation of pyridines with alkynes: (a) M. Murakami
and S. Hori, J. Am. Chem. Soc., 2003, 125, 4720; (b) Y. Nakao, K. S.
Kanyiva and T. Hiyama, J. Am. Chem. Soc., 2008, 130, 2448; (c) C.-C. Tsai,
W.-C. Shih, C.-H. Fang, T.-G. Ong and G. P. A. Yap, J. Am. Chem. Soc.,
2010, 132, 11887. For reviews on directed C–H functionalizations:
(d) G. Rousseau and B. Breit, Angew. Chem., Int. Ed., 2011, 50, 2450;
(e) G. Rouquet and N. Chatani, Angew. Chem., Int. Ed., 2013, 52, 11726;
( f ) S. R. Neufeldt and M. S. Sanford, Acc. Chem. Res., 2012, 45, 936.
6 For recent reviews on dehydrogenative Heck: (a) J. Le Bras and
J. Muzart, Chem. Rev., 2011, 111, 1170; (b) C. S. Yeung and V. M. Dong,
Chem. Rev., 2011, 111, 1215; (c) S. I. Kozhushkov and L. Ackermann,
Chem. Sci., 2013, 4, 886; (d) Y. Wu, J. Wang, F. Mao and F. Y. Kwong,
Chem. – Asian J., 2014, 9, 26.
7 (a) T. Satoh and M. Miura, Chem. – Eur. J., 2010, 16, 11212; (b) D. A. Colby,
R. G. Bergman and J. A. Ellman, Chem. Rev., 2010, 110, 624; (c) G. Song,
F. Wang and X. Li, Chem. Soc. Rev., 2012, 41, 3651; (d) F. W. Patureau,
J. Wencel-Delord and F. Glorius, Aldrichimica Acta, 2012, 45, 31.
8 For a review: C. Wang and Y. Huang, Synlett, 2013, 145.
9 (a) F. W. Patureau, T. Besset and F. Glorius, Angew. Chem., Int. Ed.,
2011, 50, 1064. See also: (b) K. Ueura, T. Satoh and M. Miura, Org.
Lett., 2007, 9, 1407.
Entry
R
Substrate t (h) Prod. Yielda (%) E/Zb
1
2
3
4
5
6
Et
C6H5
28
29
30
1a
4
16
4
1
1
31
32
33
2
11
34
57
0
89
498 : o2
—
90 : 10
CH2CH2C6H5
CH2C6H5
CH2( p-MeOC6H4) 1b
CH2( p-CF3C6H4) 1c
35c (86)d 498 : o2
22c (69)d 498 : o2
44c (79)d 498 : o2
1
a
b
c
Isolated yields. Determined by 1H NMR. GC yields after 1 h
d
(n-C16H34 as internal standard). Isolated yield after 4 h.
Scheme 3 Selective deprotection and catalytic hydrogenation of 2.
phenethyl group (benzyl homolog) restored the reactivity, albeit
with loss of stereocontrol (89% yield, E/Z-33 = 9 : 1, entry 3).
Understanding that the benzyl group has an active role in the
catalytic cycle, a kinetic study was performed to probe its
electronic sensitivity. Three electronically different N-benzyl-
type derivatives [benzyl, p-methoxybenzyl and p-(CF3)benzyl]
were subjected to the model reaction with methyl acrylate for
1 h (Table 2, entries 4–6). It was apparent that electron poor
substrates reacted slightly faster than electron-rich one, but in
all cases useful yields were obtained in 4 h (69–86%).
Scheme 3 illustrates the chemoselective N-deprotection of 2
to give product 35 (70% yield), and the selective hydrogenation
of the exocyclic double bond of 2 to afford 3 (74%).
10 (a) X. Wei, F. Wang, G. Song, Z. Dub and X. Li, Org. Biomol. Chem.,
2012, 10, 5521. See also: (b) G. Song, X. Gong and X. Li, J. Org. Chem.,
2011, 76, 7583.
11 See ESI† for X-ray structure of a Rh-complex of this type.
12 For examples of COPy-assisted C–H reactions: (a) V. G. Zaitsev,
D. Shabashov and O. Daugulis, J. Am. Chem. Soc., 2005, 127, 13154;
(b) G. He and G. Chen, Angew. Chem., Int. Ed., 2011, 50, 5192;
(c) L. D. Tran, I. Popov and O. Daugulis, J. Am. Chem. Soc., 2012,
134, 18237; (d) S.-Y. Zhang, G. He, W. A. Nack, Y. Zhao, Q. Li and
G. Chen, J. Am. Chem. Soc., 2013, 135, 2124; (e) R. Odani, K. Hirano,
T. Satoh and M. Miura, J. Org. Chem., 2013, 78, 11045.
13 For a rare exception: A. M. Suess, M. Z. Ertem, C. J. Cramer and
S. S. Stahl, J. Am. Chem. Soc., 2013, 135, 9797.
14 See, for instance: (a) M. L. Falck-Pedersen and K. Undheim, Acta
Chem. Scand., 1998, 52, 1327; (b) K.-N. Cho, S.-J. Park and K.-I. Lee,
Bull. Korean Chem. Soc., 2004, 25, 924.
In summary, we have developed a RhIII-catalyzed tandem
oxidative olefination/annulation of picolinamides enabling rapid
access to pyrrolo[3,4-b]pyridines. Good structural versatility in
both alkene and heteroarene coupling components, high func-
tional group tolerance and excellent regio- and stereocontrol
were achieved.
15 J. Zhou, B. Li, Z.-C. Qian and B.-F. Shi, Adv. Synth. Catal., 2014, 356, 1038.
16 Isolated compound 3 did oxidize to 2 under the reaction conditions,
suggesting that it could be an intermediate in its formation (see ESI†).
17 The E configuration of 2 was determined by X-ray diffraction (ESI†).
18 A. S. Tsai, M. Brasse, R. G. Bergman and J. A. Ellman, Org. Lett.,
2011, 13, 540.
We thank Spanish Government (MINECO, CTQ2012-35790)
and Madrid regional government (AVANCAT, S2009/PPQ-1634)
´
for financial support. N.R. thanks the MICINN for a Ramon y
Cajal contract and the Marie Curie Foundation (CIG: CHAAS-
304085). We thank Javier Echavarren for his contribution to
this project.
19 The reaction of 1a with a 1 : 1 mixture of styrene and methyl acrylate
(1 equiv. of each) led to decreased conversion (68% of 2, see ESI†).
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Chem. Commun., 2014, 50, 6105--6107 | 6107