Organic Letters
Letter
Scheme 6. Mechanism of Rearrangement to
Tetrahydroquinoline
REFERENCES
■
(1) (a) Sharma, V.; Kumar, P.; Pathak, D. J. Heterocycl. Chem. 2010, 47,
491. (b) Kaushik, N. K.; Kaushik, N.; Attri, P.; Kumar, N.; Kim, C. H.;
Verma, A. K.; Choi, E. H. Molecules 2013, 18, 6620. (c) Zhang, M.-Z.;
Chen, Q.; Yang, G.-F. Eur. J. Med. Chem. 2015, 89, 421. (d) Ishikura, M.;
Abe, T.; Choshi, T.; Hibino, S. Nat. Prod. Rep. 2013, 30, 694.
(e) Kochanowska-Karamyan, A. J.; Hamann, M. T. Chem. Rev. 2010,
110, 4489.
(2) (a) Taber, D. F.; Tirunahari, P. K. Tetrahedron 2011, 67, 7195.
(b) Inman, M.; Moody, C. J. Chem. Sci. 2013, 4, 29. (c) Vicente, R. Org.
Biomol. Chem. 2011, 9, 6469. (d) Gribble, G. W. J. Chem. Soc. Perkin 1
2000, 1045. (e) Cacchi, S.; Fabrizi, G. Chem. Rev. 2011, 111, PR215.
(f) Bartoli, G.; Dalpozzo, R.; Nardi, M. Chem. Soc. Rev. 2014, 43, 4728.
(3) (a) Robinson, B. Chem. Rev. 1963, 63, 373. (b) Robinson, B. Chem.
Rev. 1969, 69, 227. (c) Robinson, B. The Fischer Indole Synthesis; Wiley,
1982.
(4) (a) Larock, R. C.; Yum, E. K. J. Am. Chem. Soc. 1991, 113, 6689.
(b) Larock, R. C.; Yum, E. K.; Refvik, M. D. J. Org. Chem. 1998, 63, 7652.
(c) Zeni, G.; Larock, R. C. Chem. Rev. 2006, 106, 4644.
(5) (a) Alex, K.; Schwarz, N.; Khedkar, V.; Sayyed, I. A.; Tillack, A.;
Michalik, D.; Holenz, J.; Díaz, J. L.; Beller, M. Org. Biomol. Chem. 2008,
6, 1802. (b) Arcadi, A.; Cacchi, S.; Carnicelli, V.; Marinelli, F.
Tetrahedron 1994, 50, 437. (c) Pawlak, J. M.; Khau, V. V.; Hutchison,
(Scheme 4) while preserving them in the next synthetic steps.
This represents a marked departure from the previous work,
where mainly hydrocarbon-substituted indoles could be
obtained. The intermediacy of an iminium cation enables the
use of a wider array of nucleophiles than only Grignard reagents,
which have been used under rather forcing conditions.7 The
method described is carried out in a straightforward and rapid
fashion, permitting the synthesis of large libraries of compounds
in a timely manner. A diverse set of nucleophiles can be
employed, including C- and S-nucleophiles, which leads to
greater diversification of the products.
In summary, we have developed an expeditious method of
synthesizing 2,3-disubstituted indoles from commercially
available isatins regiospecifically. The methodology is charac-
terized by high functional group tolerance and employs the
readily available Schwartz’s reagent as the reducing agent. It
opens up an attractive route to a variety of 2,3-disubstituted
indoles and has the potential to aid in the synthesis of
pharmacologically and synthetically relevant indole derivatives.
We have also described a new diastereoselective synthesis of
highly substituted tetrahydroquinolines.
D. R.; Martinelli, M. J. J. Org. Chem. 1996, 61, 9055. (d) Kruger (nee
́
̈
Alex), K.; Tillack, A.; Beller, M. Adv. Synth. Catal. 2008, 350, 2153.
(6) (a) Silva, J. F. M. da; Garden, S. J.; Pinto, A. C. J. Braz. Chem. Soc.
2001, 12, 273. (b) Garden, S. J.; da Silva, R. B.; Pinto, A. C. Tetrahedron
2002, 58, 8399.
(7) Dou, X.; Yao, W.; Wen, S.; Lu, Y. Chem. Commun. 2014, 50, 9469.
(8) (a) Spletstoser, J. T.; White, J. M.; Tunoori, A. R.; Georg, G. I. J.
Am. Chem. Soc. 2007, 129, 3408. (b) Schedler, D. J. A.; Li, J.; Ganem, B. J.
Org. Chem. 1996, 61, 4115. (c) Oda, Y.; Sato, T.; Chida, N. Org. Lett.
2012, 14, 950. (d) Nakajima, M.; Oda, Y.; Wada, T.; Minamikawa, R.;
Shirokane, K.; Sato, T.; Chida, N. Chem. - Eur. J. 2014, 20, 17565.
(9) Connolly, T. J.; Durst, T. Can. J. Chem. 1997, 75, 542.
(10) (a) Jensen, A. E.; Dohle, W.; Sapountzis, I.; Lindsay, D. M.; Vu, V.
A.; Knochel, P. Synthesis 2002, 2002, 565. (b) Calí, P.; Begtrup, M.
Synthesis 2002, 2002, 63. (c) Sapountzis, I.; Knochel, P. Angew. Chem.,
Int. Ed. 2002, 41, 1610.
(11) (a) Povarov, L. S. Russ. Chem. Rev. 1967, 36, 656. (b) Kouznetsov,
V. V. Tetrahedron 2009, 65, 2721. (c) Fochi, M.; Caruana, L.; Bernardi,
L. Synthesis 2014, 46, 135.
(12) Sridharan, V.; Suryavanshi, P. A.; Menen
2011, 111, 7157.
́
dez, J. C. Chem. Rev.
ASSOCIATED CONTENT
■
S
* Supporting Information
The Supporting Information is available free of charge on the
1
Detailed synthetic procedures, characterization, and H
AUTHOR INFORMATION
■
Corresponding Author
Notes
The authors declare no competing financial interest.
ACKNOWLEDGMENTS
■
Financial support for this research, provided by the National
Science Centre, Grant No. OPUS 2013/11/B/ST5/01188, is
gratefully acknowledged.
C
Org. Lett. XXXX, XXX, XXX−XXX