detailed here. For example, the â-bromo-aldehyde 2818
(entries 9 and 10, Table 1) cross-couples with 1 (R ) H) or
1 (R ) OMe) to give compounds 29 and 31, respectively,
which engage in the usual reductive cyclization process, thus
affording 7,8-dihydrobenzo[k]phenanthridine (30)18 and its
3-methoxy derivative 32, respectively. In a related vein, the
natural product trisphaeridine (35)19 was readily prepared
(entry 11), in two steps and via intermediate 34,20 by initial
cross-coupling of commercially available 6-bromopiperonal
(33) with 1 (R ) H). Alternate and less common modes of
ring fusion were achieved by cross-coupling tetralone 3621
with 1 (R ) H) (entry 12) to give the aryl-substituted
tetralone 37, which participated in a reductive cyclization
reaction to give the 5,6-dihydro-4H-benz[kl]acridine deriva-
tive 38. 2-Formyl-3-iodo-indole 3922 engaged in the expected
cross-coupling reaction with 1 (R ) H) (entry 13) to give
product 40, which underwent smooth reductive cyclization
to give 7H-indolo[2,3-c]quinoline (41).23
Table 2. 2-Quinolone and Phenanthridinone Synthesis via a
Pd[0]-Mediated Ullmann Cross-Coupling/Reductive Cyclization
Sequencea
â-
cross-
reductive
cyclization
product
bromo-
bromo- coupling
%
%
entry nitroarene
ester
product yield
yield
1
2
3
4
5
6
1 (R ) H)
1 (R ) H)
1 (R ) H)
1 (R ) H)
1 (R ) H)
1 (R ) H)
42
45
48
51
54
57
43
39
ndc
83
36
48
40
44
47
50
53
56
59
78
46b
28d
49
52
55
58b
62
85
53
92e
a Full experimental procedures are given in Supporting Information.
b This product was accompanied by that arising from homo-coupling of
the precursor â-bromo-ester. c nd ) not determined. d Yield over two steps.
e Yield based on recovered starting material.
Thus, the ester, 42,24 derived from aldehyde 12, can be cross-
coupled, under the palladium[0]-catalyzed Ullmann condi-
tions, with 1-bromo-2-nitrobenzene (1, R ) H) to give the
nitro-ester 43 (entry 1), which engages in reductive cycliza-
tion on exposure to dihydrogen in the presence of palladium
on carbon, thereby affording the 2-quinolone 44.25 Phenan-
thridinones are similarly accessible. Thus, cross-coupling of
1 (R ) H) with commercially available methyl 2-iodo-
benzoate (45) afforded biaryl 4626 (entry 2). The latter
compound engaged in reductive cyclization under the usual
conditions to give the parent system 47, which proved to be
identical with commercially available samples. The amino-,
methoxy-, and carbomethoxy-substituted derivatives, 50,27
53,28 and 56, are all equally accessible via the reaction
sequences implied in entries 3, 4, and 5, respectively, of
Table 2 and involving the commercially available bromo-
benzoates 48, 51, and 54 as starting materials. This chemistry
has been readily extended to the rapid preparation of the
alkaloid crinasiadine (59)19 (entry 6, Table 2). Thus, cross-
coupling of compound 1 with the bromo-ester 5729 afforded
(14) These compounds were prepared using modifications of the methods
reported in the following papers: (a) Bovonsombat, P.; McNelis, E.
Tetrahedron 1993, 49, 1525. (b) Piers, E.; Grierson, J. R.; Lau, K. C.;
Nagakura, I. Can. J. Chem. 1982, 60, 210. Full details of these preparations
will be reported in due course.
(15) Vieweg, H.; Wagner, G. Pharmazie 1979, 34, 785.
(16) Katritzky, A. R.; Arend, M. J. Org. Chem. 1998, 63, 9989.
(17) Kar, G. K.; Karmakar, A. C.; Makur, A.; Ray, J. K. Heterocycles
1995, 41, 911.
(18) Gilchrist, T. L.; Healy, A. M. M. Tetrahedron 1993, 49, 2543.
(19) Banwell, M. G.; Cowden, C. J. Aust. J. Chem. 1994, 47, 2235.
(20) Kallianpur, C. S.; Merchant, J. R. J. Indian Chem. Soc. 1961, 38,
27.
The chemistry detailed above can be readily extended to
the synthesis of 2-quinolones and phenanthridinones by
employing â-bromo-esters as coupling partners (Table 2).
(21) Bohlmann, F.; Fritz, G. Chem. Ber. 1976, 109, 3371.
(22) Zhang, H.; Larock, R. C. J. Org. Chem. 2002, 67, 9318.
(23) Clemo, G. R.; Felton, D. G. I. J. Chem. Soc. 1951, 671; Chem.
Abstr. 1951, 45, 9060c.
(24) Jousseaume, B.; Villeneuve, P. Tetrahedron 1989, 45, 1145.
(25) Bailey, A. S.; Seager, J. F. J. Chem. Soc., Perkin Trans. 1 1974,
763.
(6) Banwell, M. G.; Kelly, B. D.; Kokas, O. J.; Lupton, D. W. Org.
Lett. 2003, 5, 2497.
(7) Lilienkampf, A.; Johansson, M. P.; Wahala, K. Org. Lett. 2003, 5,
3387 and references therein.
(8) (a) Arnold, Z.; Holy, A. Collect. Czech. Chem. Commun. 1961, 26,
3059. (b) Robertson, I. R.; Sharp, J. T. Tetrahedron 1984, 40, 3095.
(9) Ali, N. M.; McKillop, A.; Mitchell, M. B.; Rebelo, R. A.; Wallbank,
P. J. Tetrahedron 1992, 48, 8117.
(26) Muth, C. W.; Elkins, J. R.; DeMatte, M. L.; Chiang, S. T. J. Org.
Chem. 1967, 32, 1106.
(10) Eisch, J. J.; Gopal, H.; Kuo, C. T. J. Org. Chem. 1978, 43, 2190.
(11) Curran, D. P.; Kuo, S. C. J. Org. Chem. 1984, 49, 2063.
(12) Case, F. H. J. Org. Chem. 1956, 21, 1069.
(13) Nicolaou, K. C.; Dai, W.-M. J. Am. Chem. Soc. 1992, 114, 8908
and references therein.
(27) Migachev, G. I.; Grekhova, N. G.; Terent’ev, A. M. Khimiya
Geterotsiklicheskikh Soedinenii 1981, 388; Chem. Abstr. 1981, 95, 42866d.
(28) Swenton, J. S.; Ikeler, T. J.; Smyser, G. L. J. Org. Chem. 1973, 38,
1157.
(29) Brown, E.; Robin, J. P.; Dhal, R. Tetrahedron 1982, 38, 2569.
Org. Lett., Vol. 6, No. 16, 2004
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