Cyclohexenol annulation
3949
water, sat NaClaq, dried over MgSO4, filtered, and concentrated
to afford 0.070 g of brown oil. Column chromatography on silica
gel (elution with ether-pentane) gave 0.030 g (30%) of 14 as a pale
yellow oil: IR (CH2CI9 3600, 3045, 2985, 2960, 2935, 1420,
1020, and 890cm-t; ~H NMR (250MHz, CDCI3) 8 0.90 (t, 3H,
H=7.1Hz), 1.16--I.69 (m, 9H), 1.66 (br s, 3H), 1.87-2.14 (m,
4 H), and 5.25-5.28 (m, I H); ~C NMR (22.5 MHz, CDCI3)
133.7, 118.5, 70.0, 41.1, 38.0, 33.4, 27.4, 25.3, 23.3, and 14.1.
30a: IR (tf) 3340, 3020, 2920, 2830, 1665, 1645, 1430, 1370, 1030,
900, 890, 855,795,750, and 725 cm-~; ~H NMR (250 MHz, CDCI~)
1.47-2.14 (m, 7H), 1.73 (m, 3H, CH~), 2.30-2.41 (m, I H), 2.79
(m,l H), 3.86 (dd, 1 H, J =6.7, 12.9 Hz), 5.21-5.26 (m, 1H), and
5.66-5.77 (m, 2 H); ~C NMR (62.8 MHz, CDCI3) 8 135.5, 127.4,
126.7, 118.1, 66.7, 39.4, 38.9, 33.2, 22.5, 22.4, and 21.2; an exact
mass determination gave role 164.1192 (calc. for C~H~sO,
164.1201).
3Oh: IR identical with 30a; ~H NMR (250 MHz, CDCI~) 8 1.69
(m, 3 H, CH3), 1.20-2.33 (m, 8 H), 2.75 (m, I H), 3.98 (ddd, 1 H,
J = 4.3, 5.9, 9.9 Hz), 5.19-5.25 (m, I H), and 5.72-5.88 (m, 2 H)', ~C
NMR (62.8 MHz, CDCI~)~ 135.3, 128.5, 127.9, 117.7, 69.8, 40.5,
39.3, 30.5, 24.9, 20.9, and 17.0.
2,2A-Trimethyl-3-cyclohexenol (15). Rearrangement of
(0.131g, 0.95mmol) at 25° for 48hr according to method
8
C
furnished 0.0Mg (63%) of 15 as a pale yellow oil: IR (tf) 3360,
2950, 2930, 2860, 1640, 1450, 1370, 1050, 910, 830 and 730cm-~;
IHNMR (250MHz, CDCI3) ~ 0.95 (s, 3H), 1.01 (s, 3H), 1.60-
!.80 (m, 3H), 1.63 (m, 3H, CHj), 2.0 (m, 2H), 3.53
(dd, I H, J = 3.6, 9.0Hz), and 5.05-5.06 (m, I H); ~3C NMR
(22.5 MHz, CDCI3) 8 131.2, 130.6, 75.1, 36.5, 28.4, 27.2, 23.2 and
22.9; an exact mass determination gave m/e 140.1185 (calc. for
5-Butyl-2-hydroxybicyclo[4.4.0]-4,7-decadiene (31a,b)
Rearrangement of 25a,b (0.102g, 0.5retool) according to
method C provided 0.088g (85%) of 31a and 31b (30:70) as a
colorless oil: IR (tf) 3340, 3020, 2945, 2920, 2850, 1655, 1645, C9HI60, 140.1201).
1450, 1070, 1035, 990, and 730cm-~; IH NMR (250 MHz, CDCI3)
8 0.90 (t, 3 H, J = 7.0 Hz), 1.25-2.41 (m, 14 H), 2.81 (m, I H), 3.86
(dd, 1 H, 31a, J =7.3, 12.5 Hz), 3.98 (ddd, 1 H, 31b, J-- 4.0, 5.9,
9.9Hz), 5.20-5.21 (m, I H), and 5.70-5.88 (m, 2H); 13C NMR
(62.8 MHz, CDCI~) from analysis of mixtures of 31a and 31b: 31a
8 139.7, 127.6, 126.8, 117.1, 66.9, 39.1, 37.6, 34.1, 33.4, 30.0, 22.6,
22.4, and 13.9; 31b 8 139.5, 128,8, 127.8, 116.8, 70.0, 39.4, 38.7,
34.3, 30.6, 30.I, 25.1, 22.4, 17.1, and 13.9; an exact mass deter-
mination gave role 206.1683 (calc. for Cf4H:,.zO: 206.1671).
5-Butyl-4-methyl-3-cyclohexenol (32a,b). Rearrangement of
26a,b (0.166g, 1.0mmol) at 700 for 9hr according to method B
provided 0.155g (92%) of 37,a and 32b (68:32; 32a tentatively
assigned as major isomer) as a pale yellow oil: IR (tf) 3320, 3030,
2950, 2920, 2855, 1660, •450, 1370, 1060, 1030, and 800cm-~; ~H
NMR (250 MHz, CDCI3) 8 0.90 (t, 3 H, J = 6.7 Hz), 1.19-2.43 (m,
12 H), 1.67 (m, 3 H, 32b, CH3), 1.72 (m, 3 H, 32a, CH3), 3.75-3.87
(m, I H, 32b), 3.92--4.02 (m, 1 H, 32a), and 5.24-5.30 (m, I H); J3C
NMR (22.5 MHz, CDCI3) 32a only: ~ 137.3, 118.7, 64.5, 37.9, 35.2,
34.7, 32.4, 29.5, 22.8, 21.6, and 14.0; an exact mass determination
gave m/e 168.1518 (calc. for C,H2oO, 168.1514).
2 - Hydroxy - 5 - mahylbicyclo[4.4.0l - 5 - decene (16, 17).
Rearrangement of 9 (0.166 g, 1.0 retool) at 250 for 20 hr according
to method C provided 0.126g (75%) of 16 and 17 (94:6) as a pale
yellow oil. A sample of 16 (containing ca. 3% 17) was obtained by
rearrangement of 33a (3 equiv KH, I :1 THF-HMPT, 25°, I hr). A
pure sample of 17 was prepared by Li-secBusBH reduction of
the ketone obtained from 16 and 17 via PDC oxidation.
16: IR (tf) 3340, 2920, 2840, 1,140, 1030, 900 and 730cm-~;
~HNMR (250 MHz, CDCI3) 8 0.88-2.16 (m, 13H), 1.62 (m, 3H,
CH :..' ~3-2.71 (m, 1 H), and 3.49 (ddd, 1 H, J = 3.2, 6.4, 9.7 Hz);
"C NklR (22.5 MHz, CI)CI3) 8 130.6, 123.3, 73.7, 46.9, 32.7, 30.1,
29.8, 29.6, 27.2, 26.2, and 18.5; an exact mass determination gave
role 166.1359 (calc. for CHH~sO, 166.1358).
17: M.p. 70--72°; IR (CHCI3) 3600, 3440, 2920, 2850, 1515, 1440,
1380, 1040, and 920 cm-I; ~H NMR (250 MHz, CDCI3) 8 1.11-2.13
(m, 13 H). 1.62 (m, 3 H, CH3), 2.65-2.70 (m, 1 H), and 3.89 (ddd,
1H, J=2.9, 4.8, 8.1Hz); t3CNMR (22.5MHz, CDCI3) 131.0,
122.9, 69.5, 43.5, 30.0, 29.2, 28.6, 28.1, 27.7, 26.4, and 18.5; an
exact mass determination gave role 166.1315 (calc. for CHHzsO:
166.1358).
2-Methfl-3-cyclohexenol (18, 19). A soln of 10 (0.110g,
1.0mmol) in 8ml THF was treated with LiBH4 soln (1.15 M in
THF, 0.26 mL, 0.3 retool) at 0°. After 10 rain MeLi soln (I.32 M in
ether, 0.91 mL, 1.2 retool) and 4.5 mL of HMPT were added and
the resulting mixture was heated at 70* for 3.5 hr. The mixture
was cooled to room temp and then treated with 5mL of
15% NaOHaq and 3 mL of 30% H20: soln. The resulting soln
was stirred at 250 for 15 hr, diluted with ether, and the organic
phase was washed with water and sat NaClaq, dried over
MgSO4, filtered, and concentrated. Kugelrohr distillation (80-
100°, 45 torr) then provided 0.073g (65%) of 1816 and 19 (84:16)
as a colorless oil: IR (tf) 3340, 3020, 2930, 2870, 1645, 1450, 1040,
970, 920, and 680cm-J; ~HNMR (250MHz, CDCI3) ,~ 1.03 (d,
3 H, 19, J = 7.3 Hz), 1.08 (d, 3 H, 18, J = 7.0 Hz), 1.53-1.94 (m,
3 H), 2.01-2.39 (m, 3 H), 3.42-3.52 (m, 1 H, 18), 3.86--3.92 (m, I H,
19), 5.40-5.68 (m, 2 H); ~3C NMR (22.5 MHz, CDCI3) for lg:
130.8, 125.7.73.4, 38.8, 30.0. 24.2, and 18.7.
4-Phenyl-3-cyclohexenol (11). A soln of 6 (0.086 g, 0.5 mmol) in
2 mL of THF at - 780 was treated with Li-sec-Bu3BH soln (1.0 M
in THF, 1.0 mmol) and the resulting soln was allowed to warm to
250 over 2 hr. The mixture was diluted with water and ether, and
the organic layer was separated and washed with sat NaClaq,
dried
afford 0.277g of
over
MgSO4,
filtered,
and
concentrated
to
a
colorless oil. Column chromatography on
silica gel (elution with ether-hexane) provided 0.057 g (65%) of 11
as colorless crystals: m.p. 79--810 (lit)4 m.p. 82-84°); IR (CH2CI2)
3600, 3050, 2980, 2930, 2840, 1645, 1595, 1495, 1440, 1250, and
1065 cm-I; ~H NMR (60 MHz, CDCI~) 8 1.6--2.75 (m, 7 H), 3.8-4.2
(m, 1 H), 5.85-6.05 (m, I H), and 7.0-7.5 (m, 5 H).
1-Methyl-4-phenyl-3-cyclohexenol (12). Reaction of 6 (0.096 g,
0.55 mmol) with MeLi soln (1.07 M in ether, 1.0mL, 1.07 mmol)
according to the procedure described for the preparation of II
furnished 0.040g (38%) of 12 as colorless crystals: m.p. 48-50~;
IR (tf) 3380, 3080, 3060, 3030, 2970, 2930, 2840, 1645, 1600, 1495,
1445, 1120, I110, 905, 885, 775, 740, and 730cm-t; ~H NMR
(60 MHz, CDCI~) 8 1.3 (s, 3 H), 1.7 (s, 1 H, O.H), 1.65-1.95 (m,
2 H), 2.2-2.8 (m, 4 H), 5.9-6.15 (m, I H), and 7.15-7.6 (m, 5 H); an
exact mass determination gave role 188.1219 (calc. for Cj3Hj60,
188.1201).
Acknowledgements--We thank the National Institutes of Health
(GM 28273) for generous financial support. High resolution mass
spectra were provided by the facility supported by National
Institutes of Health Grant RR 00317 (principal investigator Prof.
K. Biemann) from the Biotechnology Resources Branch,
Division of Research Resources.
4-Methyl-3-cyclohexenol (13). Rearrangement of
7 (0.055g,
0.5 mmol) at 70' for 7 hr according to method B afforded 0.041 g
(72%) of 1315 as a colorless oil: IR (CH2CI2) 3600, 3450, 3045,
3005, 2920, 2860, 2840, 1600, 1440, 1420, 1050, 1030, and
890cm-*; ~H NMR (250 MHz, CDCI3) 8 1.56--I.70 (m, 2H), 1.63
(br s, 3 H), 1.76-2.03 (m, 4 H), 2.26-2.35 (m, 1 H), 3.86-3.96 (m,
I H), and 5.23-5.27 (m, I H); ~sC NMR (22.5 MHz, CDCI3)
133.9, 118.0, 66.8, 34.4, 31.0, 28.1, and 23.2.
REFERENCES
~C. G. Overberger and A. E. Borchert,J. Am. Chem. Soc. 82,
1oo7 (196o).
2For a review, see: H. M. Frey, Advances in Physical Organic
Chemistry (Edited by V. Gold), Vol. IV, pp. 175-179. Academic
Press; New York (1966).
3,j. A. Berson, Acc. Chem. Res. 1, 152, (1968); bj. A. Berson, Acc.
Chem. Res. 5, 406 (1972), and refs. cited.
4For examples, see: *J. A. Berson and J. W. Patton, J. Am. Chem.
Soc. 84, 3406, (1962); bR J. Ellis and H. M. Frey, Trans. Faraday
1-Butyl.4-methyl-3-cyclohexenol (14).
A soln of 7 (0.077g,
0.7mmol) in 3mL THF was treated at 0~ with n-BuLl soln
(2.39M in hexane, 0.58mL, 1.4mmol). After 5min 2mL of
HMPT was added and the resulting mixture was heated at 500 for
16 hr. The mixture was cooled to room temp, diluted with water
and ether, and the organic phase was separated and washed with
Danheiser, Rick L.
