PAPER
Structure-Odor Correlation of Novel Spiro[4.5]decan-2-ones
2251
2.12 (m, 2 H, 3-Hb, 4-H), 2.30/2.37 (dd, J = 18.5, 8.0 Hz, 1 H, 3-Ha),
( )-(4RS,5SR,9RS)-25
2.50–2.54 (m, 1 H, 1-H).
Content: 63%; Odor Threshold: 4.4 ng/L air.
13C NMR (CDCl3): = 11.6/12.9 (q, 1-CH3), 13.5/15.9 (q, 4-CH3),
22.5/22.6/22.7/23.0 (q, 7-, 9-CH3eq), 27.8/28.9/29.1/29.2 (d, C-7,
-9), 36.9/40.7 (d, C-4), 35.8/37.4/38.9/42.7/43.3/43.5/43.6/47.0 (t,
C-3, -6, -8, -10), 44.4/44.6 (s, C-5), 50.7/53.8 (d, C-1), 222.0/222.5
(s, C-2).
1H NMR (CDCl3): = 0.77 (mc, 1 H, 8-Hb), 0.81 (d, J = 7.0 Hz, 3
H, 4-CH3), 0.84 (s, 3 H, 7-CH3ax), 0.86 (s, 3 H, 7-CH3eq), 0.93 (mc,
1 H, 10-Hax), 0.97 (d, J = 6.5 Hz, 3 H, 9-CH3), 1.14 (mc, 1 H, 6-Hb),
1.43 (mc, 1 H, 8-Ha), 1.62 (mc, 1 H, 6-Ha), 1.81 (mc, 1 H, 10-Heq),
1.86 (pseudo d, J = 18.5, 1 H, 3-Hb), 1.91 (mc, 1 H, 4-H), 2.70 (dd,
J = 18.5, 7.5 Hz, 1 H, 3-Ha), 5.41 (s, 1 H, HbC=), 6.04 (s, 1 H,
HaC=).
MS: m/z (%) = 41 (40) [C2HO]+, 81 (31) [C6H9]+, 95 (26) [C10H18
–
C3H7]+, 109 (100) [C10H18 – C2H5]+, 123 (17) [C9H15]+, 136 (85)
[C10H16]+, 138 (40) [C10H18]+, 151 (4) [M – C4H9]+, 165 (6) [M –
C3H7] +, 193 (2) [M – CH3]+, 208 (15) [M]+.
NOESY (1H/1H): 4-CH3/10-Heq.
13C NMR (CDCl3): = 16.0 (q, 4-CH3), 23.2 (q, 9-CH3eq), 25.7 (d,
C-9), 25.9 (q, 7-CH3ax), 32.4 (s, C-7), 34.8 (q, 7-CH3eq), 41.0 (t, C-
10), 41.9 (d, C-4), 42.9 (t, C-3), 46.9 (s, C-5), 47.7 (t, C-8), 48.5 (t,
C-6), 117.2 (t, 1-H2C=), 153.9 (s, C-1), 208.0 (s, C-2).
Anal. Calcd for C14H24O (208.34): C, 81.71; H, 11.61. Found: C,
81.58; H, 11.74.
[(2(1 )E/Z,4E]-2-(3 ,3 ,5 -Trimethylcyclohexylidene)hex-4-en-3-
one
( )-(4RS,5RS,9SR)-25
Following the procedure described for the preparation of 14, the
Grignard reaction of ethyl 2-(3 ,3 ,5 -trimethylcyclohexylidene)-
propionate (44.9 g, 200 mmol) with allylmagnesium chloride in the
presence of LDA (600 mmol) furnished the title compound (28.9 g,
66%) as a 2E:2Z mixture (55:45).
Content: 37%; Odor Threshold: >30 ng/L air.
1H NMR (CDCl3): = 0.75 (mc, 1 H, 8-Hb), 1.01 (d, J = 7.0 Hz, 3
H, 4-CH3), 0.87 (s, 3 H, 7-CH3ax), 0.89 (s, 3 H, 7-CH3eq), 0.94 (d,
J = 7.0 Hz, 3 H, 9-CH3), 1.13 (d, J = 13.5 Hz, 1 H, 6-Hb), 1.15 (mc,
1 H, 10-Hax), 1.20 (d, J = 13.5 Hz, 1 H, 6-Ha), 1.43 (mc, 1 H, 8-Ha),
1.56 (mc, 1 H, 10-Heq), 1.74 (mc, 1 H, 4-H), 2.06 (dd, J = 18.5, 12
Hz, 3-Hb), 2.35 (dd, J = 18.5, 7.5 Hz, 1 H, 3-Ha), 5.42 (s, 1 H,
HbC=), 5.92 (s, 1 H, HaC=).
IR (neat): 1651 ( C=O, double unsat.), 972 ( C=C–H oop), 1456
cm–1 ( H–C–H).
1H NMR (CDCl3): = 0.75/0.87 (s, 3 H, 3 -CH3ax), 0.84/0.94 (d,
J = 6.5 Hz, 3 H, 5 -CH3), 0.90/1.00 (s, 3 H, 3 -CH3eq), 0.96 (mc, 1 H,
4 -Hax), 1.32 (mc, 1 H, 6 -Hax), 1.41 (mc, 1 H, 4 -Heq), 1.57–1.67 (m,
2 H, 2 -Hax, 5 -H), 1.77/1.81 (s, 3 H, 1-CH3), 1.91/1.93 (dd, J = 7.0,
1.5 Hz, 3 H, 6-CH3), 2.06/2.30 (dt, J = 13.0, 2.0 Hz, 1 H, 2 -Heq),
2.31/2.57 (dquint, J = 13.5, 2.0 Hz, 1 H, 6 -Heq), 6.12/6.14 (dq,
J = 15.5, 2.0 Hz, 1 H, 4-H), 6.77/6.79 (dq, J = 15.5, 7.0 Hz, 1 H, 5-
H).
NOESY (1H/1H): 1-CH3/2 -Heq (2E-isomer, 55%), 1-CH3 /6 -Heq
(2Z-isomer, 45%).
13C NMR (CDCl3): = 15.4/15.5 (q, C-1), 18.1/18.2 (q, C-6), 22.4/
22.7 (q, 5 -CH3), 25.0/25.1 (q, 3 -CH3ax), 29.0/29.8 (d, C-5 ), 32.2/
32.3 (q, 3 -CH3eq), 33.3/33.7 (s, C-3 ), 37.8/40.5 (t, C-6 ), 42.4/44.5
(t, C-2 ), 48.3/48.4 (t, C-4 ), 128.5/128.6 (s, C-2), 132.2/132.6 (d, C-
4), 137.6/138.0 (s, C-1 ), 144.9/145.2 (d, C-5), 201.3/201.5 (s, C-3).
NOESY (1H/1H): 4-CH3/6-Heq, 4-CH3/6-Hax.
13C NMR (CDCl3): = 13.0 (q, 4-CH3), 23.0 (q, 9-CH3eq), 25.6 (d,
C-9), 26.2 (q, 7-CH3ax), 31.8 (s, C-7), 35.1 (q, 7-CH3eq), 38.5 (t, C-
6), 40.5 (d, C-4), 41.8 (t, C-10), 42.1 (t, C-3), 46.2 (s, C-5), 48.0 (t,
C-8), 115.6 (t, 1-H2C=), 157.4 (s, C-1), 207.2 (s, C-2).
1,4,7,7,9-Pentamethylspiro[4.5]decan-2-one (26)
Following the preparation of 16, the enone 25 (4.00 g, 18.2 mmol)
was hydrogenated. Standard workup and silica gel FC (pentane–
Et2O, 19:1, Rf 0.37) furnished the pentamethylketone 26 (3.69 g,
91%).
Odor Description: earthy, patchouli, salicylate, slightly cinnamic.
Odor Threshold of the Isomeric Mixture: 6.8 ng/L air.
IR (neat): 1738 ( C=O), 1456 ( H–C–H), 1381 cm–1 ( CH3).
1H NMR (CDCl3): = 0.82/0.91 (d, J = 8.0 Hz, 3 H, 9-CH3eq), 0.89/
0.96 (s, 3 H, 7-CH3eq), 0.93/1.06 (d, J = 8.0 Hz, 3 H, 4-CH3), 0.92/
0.94 (s, 3 H, 7-CH3ax), 1.15/1.16 (d, J = 8.0 Hz, 3 H, 1-CH3), 1.35–
2.66 (m, 11 H, 1-, 4-, 9-H, 3- ,6-, 8-, 10-CH2).
MS: m/z (%) = 41 (97) [C2HO]+, 69 (98) [C4H5O]+, 95 (35) [M –
C4H5O – C4H8]+, 109 (30) [C7H9O]+, 121 (100) [C10H13O – C2H4]+,
135 (84) [C9H11O]+, 149 (39) [C10H13O]+, 177 (20) [M – C3H7]+,
191 (7) [M – C2H5]+, 205 (86) [M – CH3]+, 220 (32) [M]+.
13C NMR (CDCl3): = 13.6/15.2 (q, 1-CH3), 17.4/18.7 (q, 4-CH3),
22.5/22.9 (q, 9-CH3), 24.6/25.9 (d, C-9), 27.2/27.5/34.4/34.9 [q,
C(CH3)2], 31.5/31.8 (s, C-7), 38.4/41.2/43.1/44.8 (t, C-6,-10), 43.2/
43.3 (d, C-4), 43.9/44.0 (s, C-5), 49.5/50.4 (d, C-1), 47.8/48.8/49.4/
51.6 (t, C-3,-8), 223.2/224.4 (s, C-2).
MS: m/z (%) = 41 (35) [C2HO]+, 55 (35) [C3H3O]+, 83 (100)
[C6H11]+, 95 (24), 109 (27), 123 (39), 137 (13) [CnH2n–3]+, 150 (71)
[C11H18]+, 179 (7) [M – C3H7]+, 189 (2) [M – CH3 – H2O]+, 207 (4)
[M – CH3]+, 222 (7) [M]+.
4,7,7,9-Tetramethyl-1-methylenespiro[4.5]decan-2-one (25)
In analogy to the synthesis of 11, 2-(3 ,3 ,5 -trimethylcyclohexy-
lidene)hex-4-en-3-one (28.0 g, 127 mmol) was submitted to
Nazarov cyclization. Usual workup and silica gel FC (pentane–
Et2O, 19:1, Rf 0.42) afforded 25 (8.29 g, 31%) as a mixture of
4RS,5SR,9RS- and 4RS,5RS,9SR-diastereomer (63:37).
Odor Description: ambery-woody.
IR (neat): 1727 ( C=O), 935 ( C=C–H oop), 1456 ( H–C–H),
1642 cm–1 ( C=C).
Anal. Calcd for C15H26O (222.37): C, 81.02; H, 11.79. Found: C,
81.00; H, 11.59.
MS: m/z (%) = 41 (80) [C2HO]+, 79 (51), 93 (52), 107 (100)
[CnH2n–5]+, 121 (69) [C9H12O – CH3]+, 135 (86) [C9H11O]+, 150 (56)
+
[M – C3H6 – CO] , 163 (24) [M – C3H6 – CH3]+, 178 (42) [M –
4,7,7,9,9-Pentamethyl-1-methylenespiro[4.5]decan-2-one (27)
According to the synthesis of 14, the Grignard reaction of ethyl 2-
(3 ,3 ,5 ,5 -tetramethylcyclohexylidene)propionate (47.6 g, 200
mmol) with allylmagnesium chloride in the presence of LDA (600
mmol) provided 2-(3 ,3 ,5 ,5 -tetramethylcyclohexylidene)hex-4-
en-3-one (27.8 g, 59%). Part of this material (25.1 g, 107 mmol) was
cyclized in formic acid (130 mL), 85% H3PO4 (130 mL) and toluene
(250 mL) at 90 °C for 8 h. Standard workup and silica gel FC (pen-
C3H6]+, 191 (5) [M – C2H5]+, 205 (73) [M – CH3]+, 220 (24) [M]+.
Anal. Calcd for C15H24O (220.36): C, 81.76; H, 10.98. Found: C,
81.80; H, 11.13.
Synthesis 2002, No. 15, 2243–2253 ISSN 0039-7881 © Thieme Stuttgart · New York