Angewandte
Chemie
Table 1: (Continued)
[
b]
Entry NuH
T [8C] t [h] Product
Yield [%]
9
40
40
40
6.0
3.0
27
1
1
0
1
18
40
22
Scheme 5. Construction of N-hydroxyindole nocathiacin I model
system 3. Reagents and conditions: a) TFA/MeOH/CH Cl (3:1:2),
2
2
258C, 30 min, 68%; b) pTsOH (3.0 equiv), molecular sieves (4 ꢀ;
20 wt%), 27 (4.0 equiv), 8 (1.0 equiv), DME, 258C, 10 min; then 408C,
2 h, 44%. Boc=tert-butoxycarbonyl; TFA=trifluoroacetic acid.
1
2
50
3.0
31
Table 2: Selected physical properties for compounds 3, 8, 10, and 25.
3
D
2
3
: R =0.43 (silica gel, EtOAc/hexanes 7:3); [a] =À3.0 (c=0.5, CHCl );
f
3
[
(
[
a] Reactions were carried out on a 0.06–0.10-mmol scale in anhydrous DME
concentration: 0.12–0.16m) and the products were purified by PTLC (silica gel).
b] Yields of isolated products. [c] SnCl ·2H O (3 equiv).
IR (film) n˜ max =3354, 2978, 2919, 1707, 1490, 1460, 1437, 1390, 1360,
255, 1231, 1161, 1119, 1090, 1025, 879, 773, 743 cm ; H NMR
À1
1
1
2
2
(600 MHz, CD CN, 668C): d=9.22 (s, 1H), 8.06 (s, 1H), 7.50 (d,
3
J=7.7 Hz, 1H), 7.36 (d, J=7.7 Hz, 1H), 7.22 (t, J=7.7 Hz, 1H), 5.81 (br
1
1
s, 1H), 5.17 ( = ABq, J=11.4 Hz, 1H), 5.14 ( = ABq, J=11.4 Hz, 1H),
2
2
1
0) also participated in this reaction to furnish S-substituted
5.04 (dt, J=7.4, 4.8 Hz, 1H), 4.33 (q, J=7.0 Hz, 2H), 3.97 (s, 3H), 3.96
(dd, J=10.0, 4.8 Hz, 1H), 3.93 (dd, J=10.0, 4.8 Hz, 1H), 1.39 (s, 9H),
N-hydroxyindoles 11 and 19–21 and N’-substituted N-
hydroxyindoles 22 and 23, respectively. Interestingly, phenols
react as carbon nucleophiles in this process and form carbon–
carbon rather than carbon–oxygen bonds to give compounds
1
3
1
1
1
.35 ppm (t, J=7.0 Hz, 3H); C NMR (150 MHz, CD CN): d=174.0,
62.2, 162.0, 156.2, 147.7, 137.2, 128.9, 127.2, 127.0, 126.9, 120.9, 115.9,
3
15.2, 110.2, 80.4, 71.2, 62.1, 61.9, 54.2, 53.1, 28.4, 14.5 ppm; HRMS
+
(ESI) (%): calcd for C H BrN O SNa [M+Na ]: 620.0673; found:
2
4
28
3
8
2
4 and 25 (Table 1, entries 11 and 12). Compound 25 (Table 2)
620.0674
was recrystallized from acetonitrile and its structure was
confirmed by X-ray crystallographic analysis (Figure 1).
[
7]
8: R =0.53 (silica gel, EtOAc/hexanes 6:4); IR (film) n˜ =3389, 2954,
f max
2
1
7
1
3
1
849, 1737, 1596, 1566, 1460, 1431, 1290, 1255, 1231, 1184, 1155, 1096,
À1
1
026, 885, 802, 749 cm ; H NMR (600 MHz, CD CN): d=7.64 (s, 1H),
3
.14 (t, J=7.9 Hz, 1H), 7.11 (dd, J=7.9, 1.3 Hz, 1H), 6.85 (dd, J=7.9,
.3 Hz, 1H), 6.32 (s, 1H), 5.40 (s, 1H), 5.08 (br s, 1H), 3.61 ppm (s,
1
3
H); C NMR (150 MHz, CD CN): d=170.3, 154.8, 144.3, 132.1, 127.3,
3
23.4, 117.9, 111.8, 111.7, 98.9, 53.6 ppm; HRMS (ESI) (%): calcd for
+
C H BrNO Na [M+Na ]: 321.9685; found: 321.9684.
1
1
10
4
1
2
9
0: R =0.58 (silica gel, EtOAc/hexanes 6:4); IR (film) n˜ =3194, 2952,
f
m
a
x
848, 1710, 1525, 1433, 1353, 1312, 1255, 1226, 1185, 1122, 1047, 1024,
À1
1
09, 874, 771, 730, 690 cm ; H NMR (400 MHz, CD CN): d=9.49
3
(
br s, 1H), 7.45 (d, J=8.1 Hz, 1H), 7.39–7.23 (m, 6H), 7.18 (t,
Figure 1. ORTEP drawing of compound 25 drawn at the 50% probabil-
ity level.
13
J=8.1 Hz, 1H), 5.10 (s, 2H), 4.61 (s, 2H), 3.88 ppm (s, 3H); C NMR
150 MHz, CD CN): d=162.2, 139.9, 137.2, 129.2, 128.9, 128.3, 127.1,
(
3
1
26.9, 126.8, 121.0, 116.0, 115.9, 110.2, 72.7, 61.8, 52.9 ppm; HRMS
+
(ESI) (%): calcd for C H BrNO Na [M+Na ]: 412.0155; found:
18 16 4
Despite the presently unknown origins of this rather special
and exclusive reactivity of phenolic nucleophiles towards
these reactive species (i.e. 8 and/or 9), its potential in
delivering novel molecular diversity remains considerable
and warrants further exploration.
Having developed this technology, we then proceeded to
apply it to the synthesis of the nocathiacin I model system 3,
which contains the N-hydroxyindole structural motif and one
of the thiazole rings of the natural product. Scheme 5 outlines
the successful execution of this explorative study. Thus, the
412.0155
2
2
8
5: R =0.42 (silica gel, EtOAc/hexanes 6:4); IR (film) n˜ =3414, 2934,
835, 1708, 1675, 1615, 1489, 1440, 1396, 1347, 1287, 1249, 1085, 1030,
94, 746 cm ; H NMR (600 MHz, CD CN): d=9.21 (s, 1H), 7.51 (d,
f
m
a
x
À1
1
3
J=7.9 Hz, 1H), 7.28 (d, J=7.9 Hz, 1H), 7.21 (t, J=7.9 Hz, 1H), 6.46 (d,
J=8.6 Hz, 1H), 6.38 (s, 1H), 5.92 (d, J=8.6 Hz, 1H), 4.62 (s, 2H), 3.86
1
3
(s, 3H), 3.82 (s, 3H), 3.74 ppm (s, 3H); C NMR (150 MHz, CD
d=162.5, 147.5, 146.0, 139.7, 138.0, 128.6, 127.3, 126.5, 126.4, 121.2,
19.2, 118.6, 116.3, 110.4, 107.5, 60.4, 56.7, 52.6, 24.7 ppm; HRMS (ESI)
CN):
3
1
+
(%): calcd for C H BrNO Na [M+Na ]: 458.0210; found: 458.0200
19 18 6
Angew. Chem. Int. Ed. 2005, 44, 3736 –3740
ꢀ 2005 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
3739