2138
K. S. Feldman, A. Coca / Tetrahedron Letters 49 (2008) 2136–2138
À1
2
) 1726 cm ;
possible isomer. Nitration of one of the quinoline rings
occurred in each product, but for the first time, products
featuring the key C(15)–C(16) bond were detected. Optimi-
zation studies (Table 1) led to the conclusion that the best
yield of the cyclized material 17 could be achieved by treat-
ment with undiluted fuming nitric acid (entry 6). The mech-
anistic course of this transformation remains a matter of
speculation, as the central question of whether nitration
precedes or follows C(15)–C(16) bond formation is
unknown. The role of an electrocyclization (cf. 15) in this
C–C bond formation cannot be ascertained at present.
The desired pentacyclic target 3 could be derived from
6. Compound 14: orange solid. Mp 116–118 °C; IR (CH
2
Cl
) d 9.01 (d, J = 4.6 Hz, 1H), 8.42 (dd,
J = 8.5, 0.9 Hz, 1H), 7.91 (d, J = 8.1 Hz, 1H), 7.66 (ddd, J = 8.3, 7.0,
1
H NMR (400 MHz, CDCl
3
1
1
.3 Hz, 1H), 7.61 (d, J = 9.3 Hz, 1H), 7.38 (ddd, J = 8.3, 7.0, 1.2 Hz,
H), 7.32 (d, J = 9.3 Hz, 1H), 7.23 (d, J = 4.6 Hz, 1H), 6.92 (s, 1H),
1
3
4.22 (s, 3H), 4.05 (s, 3H), 3.82 (s, 3H), 3.75 (s, 3H); C NMR (75 MHz,
CDCl ) d 167.3, 156.7, 152.9, 152.4, 151.8, 149.3, 146.5, 144.4, 137.2,
30.8, 128.2, 126.1, 124.9, 122.4, 120.9, 119.7, 118.3, 116.5, 114.2, 62.6,
7.5, 53.2, 39.8; ESCI m/z (relative intensity) 404.2 (M+H, 100%),
26.1 (M+Na, 12%); HRMS calcd for C23 (M+H) 404.1610,
3
1
5
4
21 3 4
H N O
found 404.1596.
Compound 16: Mp 161–164 °C; IR (thin film) 1727 cm
(400 MHz, CDCl ) d 9.04 (d, J = 4.6 Hz, 1H), 8.50 (d, J = 8.2 Hz, 1H),
.79 (d, J = 8.3 Hz, 1H), 7.61 (t, J = 7.7 Hz, 1H), 7.58 (s, 1H), 7.37 (t,
J = 7.7 Hz, 1H), 7.30 (d, J = 4.6 Hz, 1H), 7.16 (s, 1H), 4.25 (s, 3H),
À1
1
;
H NMR
3
7
1
7a, or equally efficiently, from 17a/17b mixtures, by two
13
4
.02 (s, 3H), 3.88 (s, 3H), 3.44 (s, 3H); C NMR (100 MHz, CDCl
3
) d
simple operations. Initial reduction of the nitro function
with Fe metal led to an intermediate amine that was not
isolated. This compound(s) immediately was converted to
an intermediate diazonium product(s) en route to the par-
ent hydrocarbon via H PO -mediated reductive cleavage of
nitrogen. Thus, compound 3 was available in 10 steps from
the commercially available 5. Studies to convert 3 into a
b-ketoamide precursor to bis orthoquinone 2, and thence
to lihouidine, are ongoing.
1
66.4, 154.8, 152.5, 150.0, 149.9, 148.1, 146.3, 145.3, 142.3, 136.4,
129.8, 127.7, 125.3, 124.5, 120.7, 120.6, 114.8, 113.4, 112.1, 62.2, 57.1,
52.4, 39.2; ESCI m/z (relative intensity) 449.2 (M+H, 100%), 471.2
(
4
M+Na, 12%); HRMS calcd for C23
49.1440.
Compound 17a: Mp 68–70 °C. IR (CH
400 MHz, CDCl
H
19
N
3
O
4
(M+H) 449.1461, found
3
2
À1
1
2
Cl ) 1730 cm ; H NMR
2
(
3
) d 9.47 (d, J = 2.5 Hz, 1H), 9.03 (d, J = 4.5 Hz, 1H),
8.31 (dd, J = 9.2, 2.5 Hz, 1H), 7.76 (d, J = 8.9 Hz, 1H), 7.54 (s, 1H),
7.28 (d, J = 4.5 Hz, 1H), 4.22 (s, 3H), 3.95 (s, 3H), 3.85 (s, 3H), 3.63 (s,
3
1
1
1
3
3
H); C NMR (125 MHz, CDCl ) d 165.4, 157.0, 152.7, 151.3, 150.3,
48.4, 146.7, 145.4, 143.8, 142.0, 137.5, 128.8, 123.9, 123.1, 121.2,
19.3, 114.9, 114.4, 112.6, 62.5, 57.3, 53.0, 39.4; ESI m/z (relative
intensity) 447.1 (M+H, 100%), 404.2 (MÀCO
(M+H) 447.1305, found 447.1291.
Compound 17b: Mp 162 °C (dec); IR (thin film)1726 cm ; H NMR
300 MHz, CDCl ) d 8.72 (d, J = 5.2 Hz, 1H), 8.52 (d, J = 2.4 Hz, 1H),
.41 (dd, J = 9.2, 2.4 Hz, 1H), 7.90 (d, J = 9.2 Hz, 1H), 7.58 (s, 1H),
6.69 (d, J = 5.3 Hz, 1H), 4.19 (s, 3H), 4.18 (s, 3H), 4.04 (s, 3H), 3.88 (s,
2
, 34%); HRMS calcd for
Acknowledgment
23 18 4 6
C H N O
À1
1
Support from the National Institutes of Health, General
Medical Sciences Division (GM37681), is gratefully
acknowledged.
(
8
3
1
3
3
3
H); C NMR (125 MHz, CDCl ) d 168.7, 152.5, 151.1, 148.9, 144.5,
1
44.3, 135.9, 130.0, 128.8, 127.7, 124.3, 121.5, 121.2, 121.1, 116.9,
References and notes
115.5, 113.8, 109.8, 100.8, 61.7, 57.0, 53.7, 31.4; ESCI m/z (relative
intensity) 447.1 (M+H, 100%); HRMS calcd for C23
18
H N
O
4 6
(M+H)
1
. Bowden, B. F.; McCool, B. J.; Willis, R. H. J. Org. Chem. 2004, 69,
447.1305, found 447.1308.
À1
1
7791–7793.
Compound 3: IR (CH
2
Cl
2
) 1731 cm ; H NMR (400 MHz, CDCl
3
) d
2
3
. Kelly, T. R.; Maguire, M. P. Tetrahedron 1985, 41, 3033–3036.
. Walz, A. J.; Sundberg, R. J. J. Org. Chem. 2000, 65, 8001–
8.67 (d, J = 5.3 Hz, 1H), 7.86 (d, J = 8.4 Hz, 1H), 7.66 (ddd, J = 8.2,
6.9, 1.2 Hz, 1H), 7.59 (d, J = 8.3 Hz, 1H), 7.56 (s, 1H), 7.41 (ddd,
J = 8.1, 7.0, 1.1 Hz, 1H), 6.59 (d, J = 5.3 Hz, 1H), 4.14 (s, 3H), 4.13 (s,
8010.
1
3
4
. Torres, J. C.; Pilli, R. A.; Vargas, M. D.; Violante, F. A.; Garden, S. J.;
Pinto, A. C. Tetrahedron 2002, 58, 4487–4492.
. (a) Guram, A.; Rennels, R.; Buchwald, S. Angew. Chem., Int. Ed. Engl.
3
3H), 4.03 (s, 3H), 3.87 (s, 3H); C NMR (125 MHz, CDCl ) d 169.9,
152.3, 152.0, 148.5, 146.3, 146.2, 143.7, 143.4, 135.1, 130.6, 127.7,
125.6, 124.3, 122.4, 122.3, 115.4, 114.7, 108.4, 99.8, 61.5, 56.9, 53.2,
31.0; ESCI m/z (relative intensity) 402.1 (M+H, 100%); HRMS calcd
5
1995, 34, 1348–1350; (b) Louie, J.; Hartwig, J. Tetrahedron Lett. 1995,
36, 3609–3612.
19 3 4
for C23H N O (M+H) 402.1454, found 402.1477.