Angewandte
Chemie
imine double bond and concomitant ring closure, leading to
tetrasubstituted olefin 14 in 80% yield.
Substrate 14 was expected[8] from the outset to undergo,
upon epoxidation, a cascade reaction involving regioselective
epoxide opening and skeletal rearrangement to afford the
targeted “left” nucleus of haplophytine (2) as shown in
Scheme 3. Indeed, when 14 was treated with 1.4 equivalents
of mCPBA in CH2Cl2 at 08C, it was smoothly converted into 2
(65% yield), presumably through intermediates 15 and 16.
Although the anti stereochemistry is shown arbitrarily in
Scheme 3 for 15 and 16, no evidence exists as to their
stereochemistry, as these intermediates were neither charac-
terized nor detected.[9] The structure of compound 2 (m.p. =
255–2568C (decomp.), from benzene/acetonitrile) was based
on its spectroscopic data (Table 1) and was confirmed by X-
ray crystallographic analysis (see ORTEP drawing,
Figure 3).[7]
Figure 2. ORTEP drawing of 12. Thermal ellipsoids are shown at the
50% probability level. One molecule of CH3CN per molecule of 12
observedin the crystal lattice is omittedfor clarity.
The described chemistry provides a synthetic pathway to
the hitherto inaccessible “left domain” of haplophytine (1)
Table 1: Selected data for compounds 4, 5, 12, 13, 14, and 2.
4: Rf =0.70 (silica gel, EtOAc/hexane 1:1); m.p.=157–1598C (CH2Cl2/hexane); IR (film): nmax =3472, 2969, 2506, 1654, 1614, 1482, 1254 cmꢀ1
;
1H NMR (600 MHz, CD3CN): d=11.17 (s, 1H), 6.58 (d, J=8.7 Hz, 1H), 6.57 (d, J=8.7 Hz, 1H), 6.23 (s, 1H), 4.02 (t, J=8.1 Hz, 2H), 3.85 (s, 3H),
3.01 ppm (t, J=8.1 Hz, 2H); 13C NMR (150 MHz, CD3CN): d=156.2, 145.7, 132.6, 127.6, 124.7, 115.5, 110.9, 53.7, 49.1, 27.1 ppm; HRMS (ESI): calcd
for C10H12NO4 [M+H+]: 210.0761; found: 210.0775.
5: Rf =0.55 (silica gel, EtOAc/hexane 1:1); IR (film): nmax =3321, 2953, 1733, 1677, 1439, 1409, 1229 cmꢀ1; 1H NMR (600 MHz, CD3CN): d=9.05 (s,
1H), 7.45 (d, J=7.9 Hz, 1H), 7.36 (d, J=8.3 Hz, 1H), 7.13 (ddd, J=8.3, 7.2, 1.1 Hz, 1H), 7.06 (ddd, J=7.9, 7.2, 1.0 Hz, 1H), 5.31 (brs, 1H), 4.33
(brs, 1H), 3.71 (s, 3H), 3.67 (s, 3H), 3.23 (brt, J=12.4 Hz, 1H), 2.72–2.80 (m, 1H), 2.67–2.72 (m, 1H), 2.42–2.55 (m, 2H), 2.25 (dddd, J=14.3, 7.4,
7.4, 4.0 Hz, 1H), 2.10 ppm (dddd, J=14.2, 10.1, 7.4, 7.4 Hz, 1H); 13C NMR (150 MHz, CD3CN): d=173.3, 156.4, 136.4, 134.1, 126.9, 121.4, 119.1,
117.8, 111.0, 108.0, 52.1, 51.0, 51.0, 38.1, 30.4, 29.2, 20.9 ppm; HRMS (ESI): calcdfor C 17H21N2O4 [M+H+]: 317.1496; found: 317.1523.
1
12: Rf =0.33 (silica gel, EtOAc/hexane 1:1); m.p.=131–1338C (CH3CN); IR (film): nmax =3326, 2952, 1733, 1672, 1478, 1450, 1400 cmꢀ1; H NMR
(600 MHz, CD3CN): d=10.77 (s, 1H), 7.29 (d, J=7.6 Hz, 1H), 7.04 (ddd, J=7.7, 7.7, 1.2 Hz, 1H), 6.73 (ddd, J=7.6, 7.6, 1.0 Hz, 1H), 6.69 (s, 1H),
6.62 (d, J=7.9 Hz, 1H), 5.71 (brs, 1H), 4.72–4.68 (m, 1H), 4.05–3.95 (m, 2H), 3.84 (s, 3H), 3.64 (s, 3H), 3.63 (s, 3H), 3.41–3.37 (m, 1H), 3.09–3.02
(m, 1H), 3.01–2.93 (m, 2H), 2.55 (dd, J=14.3, 4.0 Hz, 1H), 2.43–2.39 (m, 2H), 2.35 (ddd, J=14.1, 5.6, 5.6 Hz, 1H), 2.17 (dddd, J=14.4, 7.2, 7.2,
5.5 Hz, 1H), 1.74 ppm (dddd, J=14.3, 11.4, 7.1, 7.1 Hz, 1H); 13C NMR (150 MHz, CD3CN): d=173.3, 157.0, 156.1, 147.8, 147.1, 132.4, 130.5, 128.6,
128.2, 128.0, 127.2, 122.3, 118.7, 109.5, 109.5, 107.8, 55.9, 55.8, 53.6, 52.0, 51.0, 49.4, 38.6, 30.7, 29.0, 27.4, 27.3 ppm; HRMS (ESI): calcdfor
C27H30N3O8 [M+H+]: 524.2027 found: 524.2072.
13: Rf =0.40 (silica gel, EtOAc/hexane 2:1); IR (film): nmax =2952, 1728, 1702, 1582, 1444, 1405, 1384 cmꢀ1; 1H NMR (600 MHz, CD3CN): d=7.58 (d,
J=7.8 Hz, 1H), 7.34 (ddd, J=8.8, 7.3, 1.7 Hz, 1H), 7.29 (s, 1H), 7.19–7.15 (m, 2H), 5.34 (dd, J=10.0, 4.2 Hz, 1H), 4.12 (ddd, J=11.1, 8.5, 6.6 Hz,
1H), 4.07–3.99 (m, 2H), 3.74 (s, 3H), 3.68 (s, 3H), 3.64 (s, 3H), 3.37 (s, 3H), 3.20 (ddd, J=14.3, 9.5, 2.9 Hz, 1H), 3.08–3.02 (m, 3H), 2.97 (brs, 3H),
2.62 (dddd, J=14.3, 7.6, 7.6, 4.3 Hz, 1H), 2.52–2.44 (m, 2H), 2.07–2.01 (m, 1H), 1.29 ppm (ddd, J=14.5, 8.9, 8.9 Hz, 1H); 13C NMR (150 MHz,
CD3CN): d=188.9, 173.3, 156.1, 156.0, 154.6, 149.9, 144.4, 143.4, 134.1, 131.2, 127.8, 127.5, 125.1, 122.4, 120.1, 117.3, 59.6, 58.7, 58.7, 55.2, 52.4,
51.9, 51.0, 50.9, 35.4, 31.3, 30.0, 29.0, 27.2 ppm; HRMS (ESI): calcdfor C 29H34N3O8 [M+H+]: 552.2340; found: 552.2393.
14: Rf =0.30 (silica gel, EtOAc/hexane 1:1); IR (film): nmax =2951, 1702, 1677, 1464, 1442, 1379, 1341 cmꢀ1; 1H NMR (600 MHz, CD3CN): d=8.12 (d,
J=8.4 Hz, 1H), 7.29 (d, J=7.6 Hz, 1H), 7.26 (ddd, J=7.9, 7.9, 1.2 Hz, 1H), 7.18 (s, 1H), 7.05 (ddd, J=7.5, 7.5, 1.1 Hz, 1H), 4.10 (ddd, J=11.1, 9.0,
6.3 Hz, 1H), 4.03 (ddd, J=11.0, 8.9, 7.3 Hz, 1H), 3.74 (s, 3H), 3.64 (s, 3H), 3.64 (s, 3H), 3.57 (s, 3H), 3.52–3.49 (m, 1H), 3.44–3.38 (m, 2H), 3.27
(dd, J=13.7, 5.7 Hz, 1H), 3.08–2.94 (m, 3H), 2.68 (ddd, J=16.3, 5.7, 2.3 Hz, 1H), 2.48 (ddd, J=15.8, 15.8, 5.8 Hz, 1H), 1.79 ppm (ddd, J=13.2,
13.2, 7.2 Hz, 1H); 13C NMR (150 MHz, CD3CN): d=165.8, 155.2, 154.6, 151.1, 144.1, 140.3, 136.6, 134.5, 130.8, 130.3, 128.0, 124.1, 123.9, 117.2,
115.0, 59.8, 58.3, 52.4, 52.2, 51.2, 48.6, 41.3, 34.4, 32.7, 28.9, 23.8 ppm; HRMS (ESI): calcdfor C 28H29N3O7Na [M+Na: 542.1898; found: 542.1910.
2: Rf =0.25 (silica gel, EtOAc/hexane 1:1); m.p.=255–2568C (decomp) (C6H6/CH3CN); IR (film): nmax =2950, 1754, 1705, 1443, 1379, 1128 cmꢀ1
;
1H NMR (600 MHz, CD3CN): d=8.14 (dd, J=8.2, 1.3 Hz, 1H), 7.28 (ddd, J=7.3, 7.3, 1.5 Hz, 1H), 7.14 (s, 1H), 7.12 (ddd, J=7.9, 7.9, 1.2 Hz, 1H),
6.91 (dd, J=7.9, 1.4 Hz, 1H), 4.17–4.08 (m, 2H), 3.76 (s, 3H), 3.67–3.62 (m, 1H), 3.64 (s, 3H), 3.62 (s, 3H), 3.36 (ddd, J=13.9, 7.0, 7.0 Hz, 1H), 3.25
(ddd, J=14.0, 11.2, 6.3 Hz, 1H), 3.08 (dd, J=7.8, 7.8 Hz, 2H) , 2.95 (ddd, J=17.5, 11.3, 6.3 Hz, 1H), 2.87 (s, 3H), 2.84 (ddd, J=12.9, 8.2, 6.8 Hz,
1H), 2.61 (ddd, J=13.2, 6.6, 6.6 Hz, 1H), 2.52 (ddd, J=15.6, 11.1, 4.6 Hz, 1H), 2.28 ppm (ddd, J=14.0, 11.1, 4.5 Hz, 1H); 13C NMR (150 MHz,
CD3CN): d=196.3, 172.3, 155.4, 154.7, 149.4, 143.6, 135.9, 135.0, 133.6, 131.2, 130.5, 127.7, 127.1, 125.3, 120.0, 117.5, 81.6, 58.3, 58.2, 52.8, 52.6,
52.5, 51.3, 39.5, 36.6, 30.7, 29.0, 20.9 ppm; HRMS (ESI): calcdfor C 28H30N3O8 [M+H+]: 536.2027; found: 536.2075.
Angew. Chem. Int. Ed. 2007, 46, 4715 –4718
ꢀ 2007 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
4717