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P. Kraft et al.
PAPER
1H,1H,13C NOESY–HSQC (C6D6): 1-Meax × 3-Hax, 1-Meax × 6¢-Heq,
3-Heq × 5¢-Hax, 5¢-Hax × 3¢-Hax, 3¢-Hax × 3-Heq, 3¢-Hax × 4-Hax, 1-Heq
× 6¢-Hax.
13C NMR (C6D6): d = 14.9 (q, 1-Me), 15.5 (q, 3¢-Me), 21.2 (t, C-5¢),
25.6 (t, C-3), 25.7 (t, C-7), 27.5 (t, C-4), 27.8 (t, C-8), 29.2 (t, C-6),
29.9 (t, C-9), 31.9 (t, C-10), 32.0 (t, C-5), 37.6 (d, C-1), 37.9 (t, C-
6¢), 38.1 (t, C-4¢), 40.3 (d, C-3¢), 51.7 (s, C-2), 127.0 (s, C-4a), 136.7
(s, C-10a), 213.7 (s, C-2¢).
Odor description: woody, floral, fruity; odor threshold: 2.2 ng/L air.
IR (neat): 1732 (C=O), 1448 (CH3), 1154 (CCC) cm–1.
1H NMR (C6D6): d = 0.80 (d, J = 7.0 Hz, 3 H, 1-Meax), 1.34 (mc, 1
H, 3-Hax), 1.35 (mc, 1 H, 8-Hb), 1.38 (mc, 1 H, 5¢-Hax), 1.40 (mc, 2
H, 4¢-H2), 1.43 (mc, 1 H, 3-Heq), 1.44–1.58 (m, 6 H, 6-H2, 7-H2, 9-
H2), 1.50 (mc, 1 H, 5¢-Heq), 1.78 (mc, 1 H, 8-Ha), 1.80 (mc, 1 H, 4-
Hb), 1.82 (mc, 1 H, 3¢-Hb), 1.84 (mc, 1 H, 5-Hb), 1.98 (mc, 1 H, 4-Ha),
2.01 (mc, 1 H, 10-Hb), 2.03 (mc, 1 H, 3¢-Ha), 2.26 (t, J = 12.0 Hz, 1
H, 10-Ha), 2.27 (t, J = 12.0 Hz, 1 H, 5-Ha), 2.33 (q, J = 7.0 Hz, 1 H,
1-Heq).
1H,1H,13C NOESY–HSQC (C6D6): 1-Meax × 5¢-Hax, 1-Meax × 5¢-
Heq.
13C NMR (C6D6): d = 15.5 (q, 1-Me), 18.5 (t, C-4¢), 26.7 (t, C-7),
26.9 (t, C-8), 27.4 (t, C-4), 27.5 (t, C-3), 28.6 (t, C-10), 29.3 (t, C-
6), 29.7 (t, C-9), 31.2 (t, C-5¢), 32.9 (t, C-5), 36.9 (d, C-1), 37.5 (t,
C-3¢), 51.4 (s, C-2), 130.1 (s, C-4a), 133.2 (s, C-10a), 213.8 (s, C-
2¢).
+
+
+
MS: m/z (%) = 41 (45) [C3H5 ], 55 (50) [C4H7 ], 67 (32) [C4H7 ], 79
(47) [C6H7 ], 91 (65) [C7H7 ], 105 (100) [C8H9 ], 121 (37) [C9H13+],
150 (42) [C11H18+], 161 (17) [C12H17+], 175 (49), 189 (51), 203 (34)
[M+ – CnH2n–1O], 231 (15) [M+ – C3H7], 246 (36) [M+ – CO], 259
(4) [M+ – CH3], 274 (74) [M+].
+
+
+
(1R*,1¢S*,3¢S*)-1,3¢-Dimethyl-3,4,5,6,7,8,9,10-octahydro-1H-
spiro(benzo[8]annulene-2,1¢-cyclohexan)-2¢-one (17)
By micropreparative GC a trace peak occurring in both the crude
products for the preparation of compounds 15 and 16, which exhib-
ited an interesting and intense odor upon GC–olfactometry, was iso-
lated in addition (ca. 100 mg). This substance 17 was found to be
very sensitive to even traces of acids, preventing a directed synthe-
sis with chromatographic purification.
+
+
+
MS: m/z (%) = 41 (38) [C3H5 ], 55 (41) [C4H7 ], 67 (30) [C4H7 ], 79
+
(50) [C6H7 ], 91 (68), 105 (78), 119 (34), 133 (56), 147 (33), 161
(23), 175 (26) [M+ – CnH2n–1O], 150 (14) [C11H18+], 190 (100)
[M+ – C3H4O], 203 (8) [M+ – CO – CH3], 218 (18) [M+ – CO], 228
(5) [M+ – H2O], 231 (11) [M+ – CH3], 246 (75) [M+].
Odor description: strong, woody-ambery, green; odor threshold:
0.59 ng/L air.
(1R*,1¢S*)-1-Methyl-3,4,5,6,7,8,9,10-octahydro-1H-spiro(ben-
zo[8]annulene-2,1¢-cyclopentan)-2¢-one (20)
Besides 19 and a mixed fraction (0.50 g, Rf = 0.14–0.16), the repeat-
ed chromatography of the product mixture also provided the diaste-
reoisomer 20 (0.46 g, Rf = 0.14) as a single compound.
1H NMR (C6D6): d = 0.74 (d, J = 7.0 Hz, 3 H, 1-Meax), 1.01 (ddd,
J = 4.5, 13.5, 13.5 Hz, 1 H, 6¢-Hax), 1.08 (d, J = 6.5 Hz, 3 H, 3¢-Me-
eq), 1.09 (mc, 1 H, 4¢-Hax), 1.23–1.60 (m, 11 H, 3-Hax, 6-H2–9-H2, 5¢-
H2), 1.62 (mc, 1 H, 4¢-Heq), 1.70 (mc, 2 H, 4-Hb, 5-Hb), 1.84 (mc, 1
H, 10-Hb), 1.85 (mc, 1 H, 4-Ha), 2.00 (ddd, J = 3.0, 6.5, 13.5 Hz, 1
H, 6¢-Heq), 2.06 (qdd, J = 6.5, 12.5, 12.5 Hz, 1 H, 3¢-Hax), 2.15 (q,
J = 7.0 Hz, 1 H, 1-Heq), 2.20 (mc, 1 H, 10-Ha), 2.21 (mc, 1 H, 3-Heq),
2.27 (mc, 1 H, 5-Ha).
Odor description: woody-ambery, mossy, green, earthy; odor
threshold: 0.80 ng/L air.
IR (neat): 1730 (C=O), 1447 (CH3), 1159 (CCC) cm–1.
1H,1H NOESY (C6D6): 1-Meax × 3¢-Meeq, 1-Meax × 3¢-Hax.
1H NMR (C6D6–CD3COCD3): d = 0.80 (d, J = 7.0 Hz, 3 H, 1-Me),
0.96 (ddd, J = 1.0, 8.0, 11.5 Hz, 1 H, 3-Heq), 1.24 (mc, 1 H, 9-Hb),
1.25 (mc, 1 H, 8-Hb), 1.29 (mc, 2 H, 7-H2), 1.35 (mc, 2 H, 6-H2), 1.39
(mc, 1 H, 8-Ha), 1.40 (mc, 1 H, 5¢-Hb), 1.47 (mc, 1 H, 9-Ha), 1.53–
1.64 (m, 2 H, 4¢-H2), 1.67 (mc, 1 H, 5-Heq), 1.68 (mc, 1 H, 4-Hb), 1.70
(mc, 1 H, 5¢-Ha), 1.77 (q, J = 7.0 Hz, 1 H, 1-H), 1.78 (mc, 1 H, 10-
Heq), 1.82 (mc, 1 H, 4-Ha), 1.86 (mc, 1 H, 3¢-Hb), 1.88 (mc, 1 H, 3-
Hax), 2.06 (mc, 1 H, 3¢-Ha), 2.10 (ddd, J = 3.0, 11.0, 12.5 Hz, 1 H,
10-Hax), 2.19 (ddd, J = 4.5, 11.5, 14.5 Hz, 1 H, 5-Hax).
13C NMR (C6D6–CD3COCD3): d = 16.3 (q, 1-Me), 17.9 (t, C-4¢),
24.4 (t, C-3), 26.7 (t, C-7), 26.8 (t, C-4), 27.3 (t, C-8), 28.8 (t, C-6),
30.0 (t, C-9), 31.1 (t, C-10), 31.9 (t, C-5), 34.8 (t, C-5¢), 37.3 (t, C-
3¢), 37.7 (d, C-1), 51.2 (s, C-2), 129.3 (s, C-4a), 134.1 (s, C-10a),
220.3 (s, C-2¢).
13C NMR (C6D6): d = 15.3 (q, 3¢-Me), 16.2 (q, 1-Me), 21.1 (t, C-5¢),
24.8 (t, C-3), 26.6 (t, C-4), 27.2, 29.1, 30.1, 30.5 (4 × t, C-6–C-9),
31.2 (t, C-10), 32.2 (t, C-5), 35.3 (t, C-6¢), 36.7 (d, C-1), 37.3 (t, C-
4¢), 42.2 (d, C-3¢), 50.2 (s, C-2), 129.2 (s, C-10a), 133.0 (s, C-4a),
214.5 (s, C-2¢).
+
+
+
MS: m/z (%) = 41 (65) [C3H5 ], 55 (72) [C4H7 ], 79 (53) [C6H7 ], 91
(76) [C7H7 ], 105 (100) [C8H9 ], 119 (31) [C9H11+], 133 (22), 147
(24), 161 (26), 175 (43), 189 (22), 203 (51), 217 (13) [M+ –
CnH2n–1O], 231 (22) [M+ – C3H7], 246 (36) [M+ – CO], 259 (3)
[M+ – CH3], 274 (71) [M+].
+
+
(1R*,1¢R*)-1-Methyl-3,4,5,6,7,8,9,10-octahydro-1H-spiro(ben-
zo[8]annulene-2,1¢-cyclopentan)-2¢-one (19)
+
+
+
In a Kugelrohr apparatus, allyl 1-(acetoxymethyl)-2-oxocyclopen-
tanecarboxylate (18; 13.5 g, 56.2 mmol),11 PPh3 (2.90 g, 11.1
mmol) and Pd2(dba)3·CHCl3 (20 mg, 0.019 mmol) were heated to
100 °C for 10 min, during which frothing was observed for the first
5 min. The temperature was then raised to 180 °C and the distillate
was collected in a cold trap for 20 min to provide 2-methylene cy-
clopentanone (4.42 g, 82%) as a colorless liquid. This freshly pre-
pared dienophile (4.42 g, 46.0 mmol) and H2O (3.0 mL) were added
MS: m/z (%) = 41 (49) [C3H5 ], 55 (53) [C4H7 ], 67 (40) [C4H7 ], 79
+
(64) [C6H7 ], 91 (83), 105 (77), 119 (35), 133 (46), 147 (35), 161
(24), 175 (27) [M+ – CnH2n–1O], 121 (67) [C9H13+], 150 (26)
[C11H18+], 190 (100) [M+ – C3H4O], 203 (10) [M+ – CO – CH3], 218
(18) [M+ – CO], 228 (6) [M+ – H2O], 231 (11) [M+ – CH3], 246 (89)
[M+].
in turn to a solution of 4-methylenespiro[2.7]decane (13; 2.50 g, Acknowledgment
16.6 mmol) and (PPh3)3RhCl (770 mg, 0.832 mmol) in dioxane (30
Thanks are due to G. Brunner for numerous complex and multidi-
mL), which had been stirred for 30 min at r.t. The resulting reaction
mixture was refluxed for 16 h, then allowed to cool to r.t., filtered
over a pad of silica gel, and concentrated in a rotary evaporator.
Chromatography of the residue on silica gel [pentane–Et2O (39:1);
Rf = 0.14–0.17] afforded the product (1.00 g, 24%) as a ca. 1:1 (19/
20) mixture of diastereoisomers. Repeated chromatography of this
material on silica gel (pentane–Et2O, 39:1) furnished the diastereo-
isomer 19 (0.61 g, Rf = 0.17) in pure form.
mensional NMR experiments, to F. Kuhn for the mass-spectrome-
tric data, to K. Grman for the determination of odor thresholds, to
H. Koch for the preparative GC isolation of compound 17, and to A.
E. Alchenberger and A.-S. Selezneff for the olfactory evaluations of
the compounds. We are furthermore indebted to J. Daly and P.
Schönholzer of F. Hoffmann-La Roche, Basel, for the X-ray crystal
structure of oxime 9. Proofreading of the manuscript by S. Derrer,
T. McStea, and M. Gautschi is also acknowledged with gratitude.
Synthesis 2006, No. 13, 2215–2223 © Thieme Stuttgart · New York