Communications
1
H), 7.14 (pseudo t (dd), Jffi9.5 Hz, 1H), 7.30 (d, J = 4.2 Hz, 1H), 7.53
(
pseudo t (dd), Jffi10.3 Hz, 1H), 7.67 (d, J = 4.2, 1H), 8.40 ppm (d, J =
1
3
9
1
3
7
.5 Hz, 1H); C NMR (75.5 MHz, CDCl ): d = 24.1, 113.4, 117.1,
3
22.0, 127.2, 133.3, 133.5, 134.8, 136.7, 137.8, 148.0 ppm; FTIR: n˜ =
085, 3021, 2957, 2923, 2853, 1591, 1560, 1487, 1419, 1389, 1358, 906,
À1
+
72, 743 cm ; MS (DCI): m/z: 177 [M+H] ; HRMS calcd for
+
[
C H Cl+H] : 177.0471; found: 177.0484; elemental analysis (%)
Scheme 4. Preparation of (ꢀ)-chamazulenecarboxylic acid (14):
a) 1. MeCH=C(OMe)OTBDMS, LiClO , CH Cl , 208C, 12 h; 2. PhSeCl,
11 9
calcd for C H Cl: C 74.79, H5.14; found: C 74.84, H5.18.
11
9
4
2
2
1
Data for selected compounds: 2: M.p. 31–328C; HNMR
À50!08C, 2 h; b) H O , pyridine, 08C, 1 h (46%, 2 steps); c) NaBH ,
2
2
4
(
300 MHz, CDCl ): d = 1.36 (d, J = 6.9 Hz, 6H), 2.66 (s, 3H), 2.83
MeOH/CeCl , 08C, 1.5 h (92%); d) 1. Burgess reagent, THF, 08C, 1 h;
3
3
(s, 3H), 3.08 (sept, J = 6.9 Hz, 1H), 7.01 (d, J = 10.7 Hz, 1H), 7.22 (d,
2
. p-chloranil, 208C, 24 h (55%); e) MeB(OH) , Pd(OAc) , dpdb,
2
2
J = 3.7 Hz, 1H), 7.42 (dd, J = 10.7, 1.8 Hz, 1H), 7.62 (d, J = 3.7 Hz,
K PO , PhMe, 1008C, 24 h (99%); f) LiOH, THF, H O, 208C, 12 h
3
4
2
1
3
1
1
1
1
H), 8.19 ppm (d, J = 1.8 Hz, 1H); C NMR (75.5 MHz, CDCl ): d =
(
94%).
3
3.0, 24.2, 24.9, 38.4, 112.9, 125.2, 125.3, 133.5, 135.0, 136.2, 136.4,
37.4, 140.0, 144.4 ppm; FTIR: n˜ = 3095, 3064, 2958, 2924, 2854, 1554,
527, 1462, 1420, 1387, 1367, 772 cm ; MS (DCI): m/z: 199 [M+H] ;
HRMS calcd for [C H +H] : 199.1487; found: 199.1482.
0: HNMR (300 MHz, CDCl 3): d = 1.34 (t, J = 7.6 Hz, 3H), 2.65
s, 3H), 2.82 (s, 3H), 2.83 (q, J = 7.6 Hz, 2H), 6.98 (d, J = 10.5 Hz,
H), 7.21 (brs, 1H), 7.38 (dd, J = 10.5, 1.9 Hz, 1H), 7.61 (br s, 1H),
.15 ppm (d, J = 1.9 Hz, 1H); C NMR (75.5 MHz, CDCl ): d = 13.0,
7.5, 24.2, 34.0, 112.9, 125.1, 125.2, 134.8, 135.9, 136.3, 136.4, 136.5,
À1
+
+
1
5
19
1
1
(
1
8
1
1
1
1
3
3
37.5, 144.4 ppm; FTIR: n˜ = 3098, 3063, 2960, 2926, 2866, 1555, 1561,
526, 1452, 1422, 1364, 772 cm ; MS (DCI): m/z: 185 [M+H] ;
HRMS calcd for [C H +H] : 185.1330; found: 185.1334; elemental
À1
+
+
1
4
16
analysis (%) calcd for C H : C 91.25, H8.75; found: C 91.44, H8.86.
1
4
16
1
1
2: HNMR (300 MHz, CDCl 3): d = 1.35 (d, J = 6.8 Hz, 6H), 2.88
s, 3H), 3.07 (sept, J = 6.8 Hz, 1H), 7.11 (d, J = 10.6 Hz, 1H), 7.29 (d,
J = 3.8 Hz, 1H), 7.31 (d, J = 3.8 Hz, 1H), 7.46 (dd, J = 10.6, 2.0 Hz,
also been efficiently prepared, thereby demonstrating four
distinctly different substitution options as well. Finally,
(
[
18e]
[18f]
acetoxy and aza derivatives 17a
and 17b
are examples
1
H), 7.80 (pseudo t (dd), Jffi3.8 Hz, 1H), 8.31 ppm (d, J = 2.0 Hz,
1
3
of novel azulenes that are readily prepared with this method-
ology.
1H); C NMR (75.5 MHz, CDCl ): d = 24.3, 24.7, 38.2, 114.7, 118.0,
3
126.0, 135.3, 135.4, 136.6, 137.4, 140.2, 141.8, 145.2 ppm; FTIR: n˜ =
093, 3064, 2958, 2924, 1556, 1529, 1461, 1422, 1389, 1362, 749 cm
MS (DCI): m/z: 185 [M+H] ; HRMS calcd for [C H ] : 184.1252;
À1
3
;
In conclusion, modern chemistry has been applied to the
long-standing problem of azulene synthesis and an efficient,
highly flexible approach has resulted. Our approach allows
controlled access to a wide variety of substituents and
substitution arrays and should prove to be among the most
broadly useful methods to prepare these important com-
pounds.
+
+
1
4
16
found: 184.1259.
4: M.p. 86–878C; HNMR (300 MHz, CDCl 3): d = 1.61 (d, J =
.2 Hz, 3H), 2.65 (s, 3H), 2.83 (s, 3H), 3.88 (q, J = 7.2 Hz, 1H), 7.00
1
1
7
(d, J = 10.7 Hz, 1H), 7.28 (d, J = 3.8 Hz, 1H), 7.44 (dd, J = 10.7,
1.9 Hz, 1H), 7.64 (d, J = 3.8 Hz, 1H), 8.22 ppm (d, J = 1.9 Hz, 1H);
C NMR (75.5 MHz, CDCl ): d = 13.0, 19.2, 24.2, 48.8, 114.3, 125.1,
27.1, 130.9, 133.9, 135.7, 135.8, 136.9, 137.6, 145.6 ppm; FTIR: n˜ =
585, 3103, 3065, 2961, 2923, 2853, 1704, 1556, 1454, 1261, 1023,
1
3
3
1
3
7
À1
+
74 cm ; MS (DCI): m/z: 229 [M+H] .
Experimental Section
Experimental procedure for the preparation of 6b from 5b: NaBH
4
Received: April 12, 2005
Published online: July 13, 2005
(43 mg, 1.13 mmol) was added to a stirred solution of 5b (200 mg,
1
.03 mmol) in MeOH/CeCl (2.80 mL, 0.40m, 1.12 mmol) at 08C. The
3
reaction mixture was stirred for 1.5 h at 08C and then treated with a
Keywords: aromatic compounds · azulenes · cycloaddition ·
natural products · synthesis design
saturated solution of aqueous NaH PO . The crude product was
2
4
.
isolated with EtOAc/pentane (1:1) in the usual manner and purified
by column chromatography on dry silica gel with diethyl ether/
pentane (40:60) to afford 198 mg (98%) of the trans alcohol as a
1
white solid. M.p. 67–688C; HNMR (300 MHz, CDCl 3): d = 1.17 (d,
J = 7.1 Hz, 3H), 1.38–1.48 (m, 1H), 2.16–2.24 (m, 2H), 2.33 (pseudo q,
Jffi7.3 Hz, 1H), 2.68–2.77 (m, 1H), 4.57 (pseudo t, Jffi7.2 Hz, 1H), 5.66
[1] S. Piesse, C. R. Hebd. Seances Acad. Sci. 1863, 57, 1016.
[2] P. A. Plattner, A. S. Pfau, Helv. Chim. Acta 1937, 20, 224 – 232;
see, also: H.-J. Hansen, Chimia 1996, 50, 489 – 496.
(
dd, J = 11.4, 3.3 Hz, 1H), 5.85–5.94 (m, 1H), 6.01 (dd, J = 11.5,
1
3
6
.9 Hz, 1H), 6.51 ppm (d, J = 11.5 Hz, 1H); C NMR (75.5 MHz,
[3] For reviews on the azulenes, see: a) M. Gordon, Chem. Rev.
1952, 52, 127 – 200; b) V. B. Mochalin, Y. N. Porshnev, Russ.
Chem. Rev. 1977, 46, 530 – 547; c) K.-P. Zeller in Methoden der
Organischen Chemie (Houben-Weyl), Vol. V/2c (Ed.: H. Kropf),
Georg Thieme, Stuttgart, 1985, pp. 127 – 418; for a recent
synthetic approach, see: d) A. L. Crombie, J. L. Kane, Jr.,
K. M. Shea, R. L. Danheiser, J. Org. Chem. 2004, 69, 8652 – 8667.
[4] a) Y. Coquerel, PhD Thesis, University of Grenoble, 2001; b) Y.
Coquerel, A. Blanc, J.-P. Deprꢀs, A. E. Greene, M.-T. Averbuch-
Pouchot, C. Philouze, A. Durif, Acta Crystallogr. Sect. C 2000, 56,
1480 – 1481; c) Y. Coquerel, A. E. Greene, J.-P. Deprꢀs, Org.
Lett. 2003, 5, 4453 – 4455; see, also: d) R. Yokoyama, S. Ito, M.
CDCl ): d = 19.2, 38.9, 40.3, 46.6, 74.6, 123.7, 125.3, 127.7, 133.6, 139.6,
3
À1
1
41.5 ppm; FTIR: n˜ = 3360, 3016, 1700 cm . A solution of the
Burgess reagent (347 mg, 1.46 mmol) in dry THF (5 mL) was added to
a stirred solution of the above alcohol (198 mg, 1.01 mmol) in dry
THF (6.0 mL) at 08C. The reaction mixture was allowed to warm to
2
08C and stirred for 1 h, whereupon p-chloranil (745 mg, 3.03 mmol)
was added and the resulting mixture was stirred for a further 24 h. The
crude product was isolated with pentane in the usual way and purified
by column chromatography on dry silica gel with pentane to give
9
2 mg (52%) of chloroazulene 6b as a blue solid. M.p. 368C;
1
HNMR (300 MHz, CDCl 3): d = 2.86 (s, 3H), 7.13 (d, J = 10.3 Hz,
5
132
ꢀ 2005 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Angew. Chem. Int. Ed. 2005, 44, 5130 –5133