G. K. B. Clentsmith et al. / Tetrahedron Letters 50 (2009) 1469–1471
1471
5-exo
NAc
CH2
NAc
H
N
NHAc
C
N
H
C
H
3
10
6-endo
c
Scheme 3.
Δ
H
C
H
C
N
Intramolecular cyclization of 10 and 12 could give rise to two
isomeric products, depending on whether 5-exo or 6-endo ring clo-
sure occurs (Scheme 3).
H2N
Δ
In fact, only the endo-cyclization product was observed, that is,
N-(acetyl)-1,2-dihydroisoquinoline (11) (entries 6 and 7), in which
the ring cyclizes in an anti-Markovnikov fashion.3 The 1H NMR
spectrum of 11 indicated a mixture of two isomers due to re-
stricted rotation about the amide bond in a ratio of 4:1, which
has been observed previously.19 Cyclization of the trimethylsilyl-
substituted 12 likewise resulted in formation of 11, although at a
dramatically slower rate. Upon standing in chloroform-d at room
temperature for several days, 11 underwent aromatization to give
isoquinoline. Isoquinoline could be formed from 11 directly by
addition of DDQ (2,3-dichloro-5,6-dicyanobenzoquinone).
The Rh(I) system presented in this Letter has been established
as a very effective catalyst for the synthesis of a series of
benzo(dipyrroles) and also an isoquinoline by means of hydroam-
ination. The atom-economy of the catalysis is notable, and repre-
sents a clear advance on classical methods of indole synthesis.
Attempts to examine the mechanistic path of the catalysis and to
adapt this system to give intermolecular hydroamination are
underway.
b
H
C
C
NH2
*
•
H2N
C
C
*
•
H
*
2
a
10
9
8
7
6
5
ppm
Figure 1. 1H NMR spectra (400 MHz, THF-d8, 60 °C) of the cyclization of 1,4-
diamino-2,5-bis(ethynyl)benzene (2) to 1,5-dihydropyrrolo[2,3-f]indole (3): (a)
starting material and catalyst 1 (*); (b) a mixture of 2, 3 and singly-cyclized
intermediate; (c) complete reaction to 3.
Supplementary data
Experimental details including precursor synthesis and catalytic
protocols appear as supplementary material and can be found in
the pdf associated with this article.
Figure 2. ORTEP representation and numbering scheme for 1,5-dihydro-2,6-
diphenylpyrrolo[2,3-f]indole (5).
References and notes
roles) in the series) were unequivocally confirmed by a single crys-
tal X-ray diffraction experiment (Fig. 2).17 Selected bond lengths
and bond angles appear in Table 2.
1. Müller, T. E.; Beller, M. Chem. Rev. 1998, 98, 675–703.
2. Pohlki, F.; Doye, S. Chem. Soc. Rev. 2003, 32, 104–114.
3. Beller, M.; Seayad, J.; Tillack, A.; Jiao, H. Angew. Chem., Int. Ed. 2004, 43, 3368–
3398.
4. Odom, A. L. Dalton Trans. 2005, 225–233.
5. Burling, S.; Field, L. D.; Messerle, B. A.; Rumble, S. L. Organometallics 2007, 26,
4335–4343.
6. Burling, S.; Field, L. D.; Messerle, B. A. Organometallics 2000, 19, 87–90.
7. Burling, S.; Field, L. D.; Li, H. L.; Messerle, B. A.; Turner, P. Eur. J. Inorg. Chem.
2003, 3179–3184.
8. Burling, S.; Field, L. D.; Li, H. L.; Messerle, B. A.; Shasha, A. Aust. J. Chem. 2004, 57,
677–680.
9. Burling, S.; Field, L. D.; Messerle, B. A.; Turner, P. Organometallics 2004, 23,
1714–1721.
10. Field, L. D.; Messerle, B. A.; Vuong, K. Q.; Turner, P.; Failes, T. Organometallics
2007, 26, 2058–2069.
The direct synthesis of 5 by the hydroamination route can be
compared with the classical Madelung indole synthesis of Geise
utilizing 2,5-dimethyl-1,4-phenylenediamine, benzoyl chloride
and KOBut, which requires conditions of elevated temperature
(>300 °C).18 At present, no rationalization can be advanced for
the rapid conversion of 4 to give 5 as reported here, given the com-
paratively slow rate of conversion of 8 to the isomeric compound 9
(Table 1, entry 4), and the fact that the catalyzed ring closure of 2-
(2-phenylethynyl)aniline to give 2-phenylindole also occurs at a
significantly reduced rate.7
11. Messerle, B. A.; Vuong, K. Q. Organometallics 2007, 26, 3031–3040.
12. Seligson, A. L.; Cowan, R. L.; Trogler, W. C. Inorg. Chem. 1991, 30, 3371–3381.
13. Müller, T. E.; Pleier, A.-K. J. Chem. Soc., Dalton Trans. 1999, 583–588.
14. Takemiya, A.; Hartwig, J. F. J. Am. Chem. Soc. 2006, 128, 6042–6043.
15. Prasad, G. K. B.; Burchat, A.; Weeratunga, G.; Watts, I.; Dmitrienko, G. I.
Tetrahedron Lett. 1991, 32, 5713–5716.
Table 2
Selected bond lengths (Å) and bond angles (°) of 1,5-dihydro-2,6-diphenylpyrrolo[2,3-
f]indole (5)
16. Berlin, A.; Bradamante, S.; Ferraccioli, R.; Pagani, G. A.; Sannicolo, F. J. Chem.
Soc., Chem. Commun. 1987, 1176–1177.
Entry
Atoms
Bond length (Å)
Atoms
Bond angle (°)
1
2
3
4
5
6
7
8
N(1)–C(1)
N(2)–C(6)
N(1)–C(10)
N(2)–C(5)
C(1)–C(2)
C(6)–C(7)
C(1)–C(11)
C(6)–C(17)
1.389(3)
1.381(3)
1.391(3)
1.398(3)
1.369(3)
1.372(3)
1.460(3)
1.463(3)
C(1)–N(1) C(10)
C(6)–N(2)–C(5)
C(2)–C(1) N(1)
C(7)–C(6) N(2)
C(1)–C(2)–C(3)
C(6)–C(7)–C(8)
N(1)–C(1)–C(11)
N(2)–C(6)–C(17)
109.41(14)
109.58(17)
108.23(17)
108.25(17)
109.14(17)
109.04(17)
123.60(18)
123.43(18)
17. Crystallographic data (excluding structure factors) for the structure in this
Letter have been deposited with the Cambridge Crystallographic Data
Centre as supplementary publication no. CCDC 694651. Copies of the data
can be obtained, free of charge, on application to CCDC, 12 Union Road,
Cambridge CB2 1EZ, UK, (fax: +44-(0)1223-336033 or e-mail:
deposit@ccdc.cam.ac.uk).
18. Chen, H. Z.; Jin, Y. D.; Xu, R. S.; Peng, B. X.; Desseyn, H.; Janssens, J.; Heremens,
P.; Borghs, G.; Geise, H. J. Synth. Met. 2003, 139, 529–534.
19. Katayama, H.; Ohkoshi, M.; Yasue, M. Chem. Pharm. Bull. 1980, 28, 2226–2228.