A. Fürstner et al.
Compound34 : A solution of cerium ammonium nitrate (CAN, 460 mg,
0.84 mmol) in degassed H2O (2.1 mL) was added to a solution of com-
pound 33 (70 mg, 0.21 mmol) in CHCl3 (2.1 mL) and DME (2.1 mL) and
the resulting mixture was vigorously stirred for 30 min. After separation
of the two phases, the aqueous layer was extracted with Et2O (32 mL),
the combined organic phases were successively washed with sat. aq.
NaHCO3 (0.5 mL) and brine (31 mL) before they were dried (Na2SO4)
and evaporated. Purification of the residue by flash chromatography
(pentanes/Et2O 20:1) afforded aldehyde 34 (44 mg, 60%) and alcohol 35
(14 mg, 25%) as colorless syrups each.
Compound 34: 1H NMR (400 MHz, CD2Cl2): d=9.80 (s, 1H), 6.87 (s,
1H), 3.13 (m, 1H), 2.76–2.61 (m, 2H), 1.95–1.83 (m, 1H), 1.72–1.16 (m,
14H), 1.62 (s, 9H), 1.06–0.93 (m, 1H), 0.87 ppm (t, J=7.1 Hz, 3H);
13C NMR (100 MHz, CD2Cl2): d=180.1, 149.9, 141.4, 134.3, 129.4, 120.1,
85.7, 36.8, 36.4, 35.5, 30.7, 28.0, 27.4, 27.2, 26.2, 25.0, 24.1, 23.2, 14.3 ppm;
IR (film): n˜ =2958, 2928, 2857, 2707, 1747, 1668, 1572, 1480, 1394, 1370,
1307, 1167, 1130, 848 cmꢀ1; MS (EI): m/z (%): 347 (9) [M +], 247 (55),
218 (11), 190 (69), 162 (16), 57 (100), 41 (21); HRMS (EI): m/z: calcd for
C21H33NO3: 347.2460; found: 347.2466 [M +].
Compound 35: 1H NMR (400 MHz, CD2Cl2): d=9.90 (brs, 1H), 9.34 (s,
1H), 6.69 (d, J=2.8 Hz, 1H), 5.07 (dt, J=10.1, 3.5 Hz, 1H), 2.93 (d, J=
3.1 Hz, 1H), 2.78 (m, 1H), 2.03–1.85 (m, 2H), 1.76–1.64 (m, 2H), [1.63–
1.48 (m), 1.48–1.36 (m), 1.36–1.16 (m), 1.11–0.99 (m) 12H], 0.87 ppm (t,
J=7.1 Hz, 3H); 13C NMR (100 MHz, CD2Cl2): d=178.7, 141.2, 131.1,
128.5, 123.1, 69.0, 39.2, 38.4, 37.7, 33.9, 30.4, 26.2, 26.1, 23.2, 22.9,
14.2 ppm; IR (film): n˜ =3450, 3260, 2922, 2854, 1635, 1566, 1465, 1421,
1377, 1260, 1146, 1127, 1031, 836, 786 cmꢀ1; MS (EI): m/z (%): 263 (100)
[M +], 245 (15), 234 (26), 220 (26), 206 (100), 192 (21), 178 (16), 164 (24),
150 (27), 136 (27), 118 (22), 94 (14), 80 (27), 69 (17), 57 (31), 41 (29).
1.3 Hz, 1H, H-22), 6.34 (s, 1H, H-2), 6.20 (dd, J=3.6, 2.6 Hz, 1H, H-23),
6.08 (s, 1H, H-19), 3.97 (s, 3H, H-25), 2.59 (m, 1H, H-11), 2.33 (br, 2H,
H-5), 1.68 (m, 1H, H-6a), 1.62–1.50 (m, 4H, H-7a, 10a, 12), 1.41–1.15 (m,
9H, H-7b, 8, 9a, 10b, 13, 14), 1.00 (m, 1H, H-6b), 0.85 (t, J=7.2 Hz, 3H,
H-15), 0.83 ppm (m, 1H, H-9b); 13C NMR (150 MHz, CD2Cl2): d=169.2
(s, C-18), 159.6 (s, C-20 or C-17), 142.9 (s, C-4), 139.2 (s, C-17 or C-20),
129.1 (s, C-21), 128.5 (s, C-1), 128.2 (s, C-3), 122.3 (d, C-24), 118.6 (d, C-
2), 116.2 (d, C-16), 112.6 (d, C-22), 110.6 (d, C-23), 95.7 (d, C-19), 58.8
(q, C-25), 38.0 (t, C-10), 37.1 (t, C-12), 36.1 (d, C-11), 30.6 (t, C-13), 28.1
(t, C-8), 28.0 (t, C-7), 27.7 (t, C-6), 27.6 (t, C-5), 23.3 (t, C-9), 23.2 (t, C-
14), 14.2 ppm (q, C-15); 15N NMR (60.8 MHz, CD2Cl2): d=ꢀ226.6,
ꢀ153.4 ppm; IR (film): n˜ =3322, 3103, 2921, 2852, 1618, 1577, 1552, 1449,
1333, 1285, 1148, 1116, 1057, 954, 890, 767, 728 cmꢀ1; MS (EI): m/z (%):
391 (100) [M +], 334 (26); HRMS (EI): m/z: calcd for C25H33N3O:
391.26236; found: 391.26242 [M +]. Treatment of the product with sat.
HCl in Et2O followed by evaporation of the solvent afforded the corre-
sponding hydrochloride (6·HCl) which showed the following spectral
properties: 1H NMR (600 MHz, CDCl3): d=12.76 (s, 1H), 12.57 (s, 1H),
12.56 (s, 1H), 7.19 (m, 1H), 6.95 (s, 1H), 6.89 (m, 1H), 6.60 (d, J=
2.6 Hz, 1H), 6.32 (dt, J=3.8, 2.3 Hz, 1H), 6.06 (d, J=1.9 Hz, 1H), 3.99
(s, 3H), 3.32 (ddd, J=14.2, 8.2, 2.5 Hz, 1H), 2.74 (ddd, J=14.2, 9.8,
2.6 Hz, 1H), 2.70 (m, 1H), 2.11 (m, 1H), 1.75–1.09 (m, 15H), 0.86 ppm
(t, J=7.2 Hz, 3H); 13C NMR (150 MHz, CDCl3): d=126.8, 126.5, 126.5,
116.8, 116.0, 92.6, 58.5, 36.8, 36.5, 35.8, 30.0, 27.1, 26.9, 26.7, 26.4, 23.6,
22.6, 14.0 ppm.
Compound41 : Prepared as described above from triflate 38 (18.0 mg,
0.0379 mmol) and boronic acid 40 (13.1 mg, 0.117 mmol); isolated in
1
form of its hydrochloride salt as dark red solid (13.1 mg, 81%). H NMR
(600 MHz, [D8]-THF): d=14.97 (brs, 1H), 14.53 (brs, 1H), 8.72 (d, J=
3.6 Hz, 1H), 7.77 (d, J=1.4 Hz, 1H), 7.26 (s, 1H), 6.90 (s, 1H), 6.69 (dd,
J=3.6, 1.5 Hz, 1H), 6.47 (s, 1H), 4.06 (s, 3H), 3.45 (ddd, J=13.8, 8.1,
2.5 Hz, 1H), 2.80 (m, 1H), 2.78 (m, 1H), 2.10 (m, 1H), 1.73 (m, 1H),
1.80–1.15 (m, 14H), 0.88 ppm (t, J=7.0 Hz, 3H); 13C NMR (150 MHz,
[D8]-THF): d=166.8, 158.2, 147.2, 146.5, 145.1, 135.2, 129.9, 128.2, 121.3,
120.0, 118.9, 114.3, 94.1, 59.4, 37.8, 37.5, 37.0, 31.1, 28.2, 27.5, 27.4, 27.3,
24.8, 23.7, 14.4 ppm; IR (film): n˜ =3255, 3090, 2920, 2851, 1620, 1571,
1542, 1417, 1334, 1283, 1231, 1156, 1089, 989, 944, 836, 775, 744 cmꢀ1; MS
(EI): m/z (%): 392 (100) [M +ꢀHCl], 349 (13), 335 (42), 307 (9); HRMS
of the free base (EI): m/z: calcd for C25H32N2O2: 392.24638; found:
392.24650 [M +].
Compound37 : A solution containing aldehyde 34 (19 mg, 0.055 mmol)
and lactam 36 (24.8 mg, 0.11 mmol) in DMSO (550 mL) was treated with
degassed aq. NaOH (2m, 200 mL) and the resulting solution was stirred
overnight at 608C. For work up, the mixture was partitioned between
water and CH2Cl2, the combined organic layers were washed with brine
(1 mL), dried (Na2SO4) and evaporated. Purification of the residue by
flash chromatography (pentanes/Et2O 4:1 ! 1:1 ! 0:1) gave 37 as a
yellow-brown solid (13 mg, 69%). 1H NMR (400 MHz, CDCl3): d=10.79
(brs, 1H), 10.16 (brs, 1H), 6.30 (s, 1H), 6.17 (d, J=2.8 Hz, 1H), 5.06 (d,
J=1.5 Hz, 1H), 3.87 (s, 3H), 3.01–2.93 (m, 1H), 2.72–2.62 (m, 2H), 2.01–
1.88 (m, 1H), [1.70–1.48 (m), 1.48–1.18 (m), 1.18–1.04 (m), 15H],
0.86 ppm (t, J=6.8 Hz, 3H); 13C NMR (100 MHz, CDCl3): d=173.0,
168.0, 138.5, 126.2, 124.7, 122.4, 115.6, 102.9, 89.8, 58.1, 37.0, 36.8, 35.9,
30.4, 27.7, 27.2, 26.6 (2C), 23.9, 22.9, 14.1 ppm; IR (KBr): n˜ =3342, 2918,
2852, 1668, 1592, 1579, 1362, 1224, 782 cmꢀ1; MS (EI): m/z (%): 342 (100)
Compound43 : Prepared as described above from triflate 38 (10.0 mg,
0.0211 mmol) and boronic acid 42 (8.1 mg, 0.0633 mmol); dark red solid
(7.0 mg, 81%). 1H NMR (400 MHz, [D8]-THF): d=7.51 (dd, J=3.7,
1.1 Hz, 1H), 7.44 (dd, J=5.1, 1.1 Hz, 1H), 7.07 (dd, J=5.1, 3.7 Hz, 1H),
6.75 (s, 1H), 6.37 (brs, 1H), 6.07 (s, 1H), 3.87 (s, 3H), 2.84 (ddd, J=14.8,
7.8, 2.7 Hz, 1H), 2.74 (m, 1H), 2.72 (m, 1H), 1.99 (m, 1H), 1.75–1.15 (m,
15H), 0.87 ppm (t, J=7.0 Hz, 3H); 13C NMR (100 MHz, [D8]-THF): d=
169.2, 160.6, 142.3, 141.9, 141.8, 130.5, 128.5, 128.42, 128.38, 127.6, 118.3,
117.7, 95.2, 58.6, 38.3, 37.7, 37.1, 31.3, 28.5, 28.4, 28.2, 27.9, 24.7, 23.7,
14.5 ppm; IR (film): n˜ =3279, 3010, 2921, 2851, 1613, 1547, 1405, 1365,
1330, 1274, 1203, 1144, 1107, 1013, 890, 703 cmꢀ1; MS (EI): m/z (%): 408
(100) [M +], 365 (9), 351 (37); HRMS (EI): m/z: calcd for C25H32N2OS:
408.22354; found: 408.22358 [M +].
[M+], 299 (22), 285 (25), 243 (21), 229 (11).
Triflate 38: Triflic anhydride (60 mL, 0.357 mmol) was added to a solution
of 37 (100 mg, 0.292 mmol) in CH2Cl2 (14.5 mL) at 08C and the resulting
mixture was stirred at that temperature for 1 h. A standard extractive
work up followed by flash chromatography (basic aluminium oxide, pen-
tanes/Et2O 10:1 ! 0:1) gave triflate 38 as a yellow syrup (100 mg, 72%)
which was immediately used in the next step without further characteri-
zation.
Butylcycloheptylprodigiosin 6:
(14.0 mg, 0.0295 mmol), boronic acid 39 (18.7 mg, 0.0886 mmol), [Pd-
(PPh3)4](2.8 mg, 0.00242 mmol) and LiCl (3.8 mg, 0.0897 mmol) in DME
A degassed solution of triflate 38
Compound45 : Prepared as described above from triflate 38 (12.0 mg,
0.0253 mmol) and boronic acid 44 (13.8 mg, 0.0758 mmol); dark red solid
(5.1 mg, 44%). 1H NMR (400 MHz, [D8]-THF): d=7.67 (d, J=1.8 Hz,
1H), 7.50 (dd, J=8.3, 2.0 Hz, 1H), 6.95 (d, J=8.3 Hz, 1H), 6.72 (s, 1H),
6.35 (brs, 1H), 6.14 (s, 1H), 3.88 (d, J=5.3 Hz, 6H), 3.83 (s, 3H), 2.85
(m, 1H), 2.80–2.67 (m, 2H), 2.04–1.89 (m, 1H), 1.76–1.14 (m, 15H),
0.87 ppm (t, J=6.8 Hz, 3H); 13C NMR (100 MHz, [D8]-THF): d=169.3,
165.8, 152.3, 150.6, 142.3, 141.2, 130.7, 129.5, 128.1, 121.0, 117.6, 117.1,
112.3, 110.9, 95.0, 58.5, 56.1, 55.9, 38.2, 37.7, 37.1, 31.3, 28.5, 28.3, 28.2,
27.8, 24.7, 23.7, 14.5 ppm; IR (film): n˜ =3311, 2919, 2849, 1619, 1585,
1567, 1551, 1515, 1252, 1234, 1141, 1107, 1021, 941, 813 cmꢀ1; MS (EI):
m/z (%): 462 (100) [M +], 405 (35); HRMS (EI): m/z: calcd for
C29H38N2O3: 462.28824; found: 462.28828 [M +].
ACHTREUNG
(0.6 mL) was warmed to 808C before degassed aq. Na2CO3 (2m, 88.5 mL)
was added. After stirring at that temperature for 1 h, the mixture was
partitioned between water and ethyl ace-
tate, the combined organic layers were
treated with aq. disodium ethylenediamine
tetraacetate (Na2·EDTA, 0.05m, 50 mL)
before they were dried (Na2SO4) and
evaporated. The residue was purified by
flash chromatography (basic aluminium
oxide; pentanes/Et2O 50:1 ! 2:1) to give 6
1
as a dark red solid (7.0 mg, 61%). H NMR
(600 MHz, CD2Cl2): d=6.82 (s, 1H, H-16),
6.72 (brs, 1H, H-24), 6.69 (dd, J=3.6,
Compound47 : Prepared as described above from triflate 38 (11.0 mg,
0.0232 mmol) and boronic acid 46 (18.2 mg, 0.0697 mmol); dark red solid
1942
ꢀ 2007 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Chem. Eur. J. 2007, 13, 1929 – 1945