Mechanism of Chorismate Mutase
J. Am. Chem. Soc., Vol. 121, No. 50, 1999 11845
128.39 δ): δ ) 168.11 (dC(R)-O), 130.55 (down, one of CHdCH),
129.88 (down, one of CHdCH), 80.95 (up, CH2d), 73.70 (down, CH-
O), 39.02 (down, CH), 35.67 and 35.54 (up, two CH2). MS (high res
EI) m/z calcd for C8H10O 122.0732, found 122.0744.
2.14 (m, 2H), 1.80 (s, 3H), 1.76 (m, 1H), 1.55 (m, 1H), 1.20 (t of d,
J ) 3.9, 13.2 Hz, 1H), 0.87 (s, 9H). 13C + APT (75 MHz, C6D6,
C6D6d128.07 δ): δ ) 158.86 (up, small, O-Cd), 133.19 (down,
CHd), 125.53 (down, CHd), 82.08 (up, CH2d), 69.57 (down, CH-
O), 39.12 (down, CH), 32.13 (up, small), 29.40 (up), 27.78 (up, small),
27.62 (down, CH3 of tBu), 22.50 (down). IR (neat): 3130, 3033, 2960,
2920, 2890, 2870, 2840, 1660, 1600, 1490, 1480, 1455, 1447, 1440,
1405, 1390, 1380, 1290. MS (high res EI): m/z calcd for C13H22O
trans-5-tert-Butylcyclohex-2-enyl Vinyl Ether (3). The compound
was synthesized according to a modified general procedure of Watanabe
and Conlon.114 Mercury(II) acetate was recrystallized from ethanol and
dried in a vacuum immediately before use. Ethyl vinyl ether was washed
with 1 M HCl and 10% NaOH, dried over Na2CO3, and stored over
sodium before use. It was distilled directly into the reaction flask (20
mL) containing trans-5-tert-butylcyclohex-2-enol (23)77 (300 mg, 1.95
mmol) under argon. Hg(OAc)2 (60 mg) was added and refluxed under
Ar for 4 h, then an additional 30 mg of Hg(OAc)2 was introduced, and
reflux was continued for another 6 h. The reaction mixture was cooled
on an ice bath, stirred with 10% Na2CO3 (20 mL) for 10 min, and
diluted with ether, and the layers were separated. The ether solution
was dried (Na2CO3) and evaporated at room temperature to give 416
mg of a colorless liquid containing ca. 10% of unreacted alcohol by
1H NMR. The crude product was dissolved in 0.4% Et3N in pentane
and quickly chromatographed at -78 °C on basic alumina prewashed
with eluent. Evaporation gave 346 mg of product stabilized with Et3N.
1H NMR (300 MHz, concentrated in CDCl3, CHCl3 ) 7.26 δ): δ )
194.1671, found 194.1663; m/z 138 C9H14O+, 137 C10H17+, 136
+
C10H16+, 121 C9H13
.
(trans-5-tert-Butyl-cyclohex-2-enyl)acetone (29). trans-5-tert-Bu-
tylcyclohex-2-enyl 1-methylvinyl ether (4) in C6D6 was sealed in a
pressure/vacuum NMR tube after a few freeze-pump-thaw cycles and
kept in an oil bath at 150 °C for 3 days. 1H NMR (400 MHz, benzene-
d6, C6D5H ) 7.16 δ): δ ) 5.68 (br s, 2H), 2.80 (br s, 1H), 2.09 (ABX
2
3
3
m, J ) 16.4 Hz, J ) 5.6 Hz, J ) 8.0 Hz, 2H), 1.84 (d of unres m,
1H), 1.68 (s, 3H), 1.3-1.7 (m). 13C + APT (75 MHz, C6D6, C6D6 )
128.3 δ): δ ) 205.99 (up, CdO), 130.62 (down, CHd), 128.26 (down,
CHd), 49.16 (up, CH2), 39.65 (up), 32.33, 31.61 (down), 30.32, 29.19
(up), 27.61 (down, CH3 of tBu). IR (neat): 1715. MS (high res EI):
calcd for C13H22O 194.1671, found 194.1669.
cis-5-tert-Butylcyclohex-2-enol (25). The compound was prepared
by means of a modified literature procedure.77 To a magnetically stirred
suspension of LiAlH4 (320 mg, 8.4 mmol) in anhydrous ether (20 mL)
was added dropwise 5-tert-butylcyclohex-2-enone (24) (912 mg, 6.0
mmol) in 3 mL of anhydrous ether at -70 °C. The cold bath was
removed, and the mixture was stirred at room temperature for 30 min.
Water (0.320 mL) was added very slowly dropwise with caution, then
10% NaOH (0.320 mL), followed by water (0.960 mL). The mixture
was filtered and washed with ether many times, and the combined
extracts were evaporated to give 863 mg of colorless oil (93% yield).
1H NMR (300 MHz, CDCl3, CHCl3 ) 7.26 δ): 5.78 (m, 1H), 5.65
(m, 1H), 5.28 (m, 1H), 2.13 (m, 1H), 2.0 (m, 1H), 1.8 (m, 1H), 1.6
(br), 1.4 (m, 1H), 1.07 (m, 1H), 0.873 (s, 9H).
3
3
3
6.35 (dd, Jcis ) 6.6 Hz, Jtrans ) 14.1 Hz, 1H), 6.03 (ddd, Jcis ) 9.9
Hz, J ) 5.4, 2.1 Hz, 1H), 5.82 (m, 1H), 4.32 (br s, 1H), 4.31 (dd,
2J ) 1.5 Hz, Jtrans ) 14.1 Hz, 1H), 4.01 (dd, J ) 1.5 Hz, Jcis ) 6.6
Hz, 1H), 2.14 (m, 1H), 2.07 (m, 1H), 1.74 (m, 1H), 1.55 (t of dd, 1H),
1.25 (t of d, 1H), 0.87 (s, 9H). 13C + APT (75 MHz, CDCl3, CDCl3 )
77.00 δ) δ ) 150.53 (down, O-CHd), 133.80 (down, CHd), 124.21
(down, CHd), 88.24 (up, CH2d), 71.93 (down, CH-OR), 37.84 (down,
CH-t-Bu), 31.75 (up, C of t-Bu), 29.03 (up, CH2), 27.08 (down, Me
of t-Bu), 26.91 (up, CH2). IR (neat): 3120, 3050, 2980, 2940, 2880,
1650, 1625, 1490, 1460, 1415, 1390, 1355, 1335, 1220, 1200, 1095.
MS (high res EI): m/z calcd for C12H20O 180.1514, found 180.1519.
3
2
3
(trans-5-tert-Butylcyclohex-2-enyl)acetaldehyde (27). trans-5-tert-
Butylcyclohex-2-enyl vinyl ether (3) in C6D6 was sealed in a capillary
tube and kept at 150 °C for 3 days. The reaction mixture was dissolved
in CDCl3 for NMR and then evaporated in air for IR and MS analysis.
NMR and IR spectra were in agreement with the literature.115 1H NMR
cis-5-tert-Butylcyclohex-2-enyl Vinyl Ether (5). The compound was
obtained by the same procedure as described above for its trans-isomer
3. cis-5-tert-Butylcyclohex-2-enol (25)77 (214 mg, 0.72 mmol), Hg-
(OAc)2 (2 × 32 mg), ethyl vinyl ether (7 mL), and 20 h reflux gave a
colorless oil after Kugelrohr distillation. 1H NMR (300 MHz, con-
3
(300 MHz, 4:1 CDCl3/C6D6, CHCl3 ) 7.26 δ): δ ) 9.88 (t, J ) 2.0
3
centrated in C6D6, C6D5H ) 7.16 δ): δ ) 6.34 (dd, Jcis ) 6.6 Hz,
Hz, 1H; CHO), 5.90 (unres m, 1H), 5.80 (unres m, 1H), 2.95 (m, 1H),
1.00-3.00 (20H). IR (neat): 1725. MS (high res EI): m/z calcd for
C12H20O 180.1514, found 180.1508.
3Jtrans ) 14.1 Hz, 1H), 5.81 (dm, 3Jcis ) 9.0 Hz, J ) 1.5 Hz, 1H), 5.61
3
3
(dm, J ) 9 Hz, 2.5 Hz, 1H), 4.43 (dd, J ) 1.2 Hz, Jtrans ) 14.1 Hz,
1H), 4.32 (fine m, 1H, CH-O), 4.05 (dd, 2J ) 1.5 Hz, 3Jcis ) 6.6 Hz,
1H), 2.06 (m, 1H), 1.67-1.79 (m, 1H), 1.50-1.62 (m, 1H), 1.27 (m,
1H), 1.16 (m, 1H), 0.71 (s, 9H). 13C + APT (75 MHz, C6D6, C6D6 )
128.39 δ): δ ) 150.71 (down, O-CHd), 130.33 (down, CHd), 128.44
(down, CHd), 88.58 (up, CH2d), 76.71 (down, CH-OR), 43.33 (down,
CH-t-Bu), 32.50 (up, C of t-Bu), 31.42 (up, CH2), 27.41 (up, CH2).
27.37 (down, CH3 of t-Bu). MS (high res EI): calcd for C12H20O
180.1514, found 180.1509.
trans-5-tert-Butylcyclohex-2-enyl Acetate (28). trans-5-tert-Butyl-
cyclohex-2-enol (23) (461 mg, 2.99 mmol) in anhydrous pyridine (5
mL, Aldrich) and acetic anhydride (5 mL, excess) was stirred overnight
at room temperature (after 1.5 h reaction had reached only 40%
completion), then poured into saturated NaHCO3 with ice, stirred for
1 h, extracted with ether, washed with saturated NaHCO3 twice, dried
(Na2SO4), and evaporated to give 534 mg of pale yellow oil, yield 91%.
Acetylation under acidic conditions (catalytic amount of H2SO4) led
to a mixture of cis- and trans-isomers. 1H NMR (300 MHz, concentrated
(cis-5-tert-Butylcyclohex-2-enyl)acetaldehyde (26). The solution of
cis-5-tert-butylcyclohex-2-enyl vinyl ether (5) in benzene-d6 was kept
3
3
in CDCl3, CHCl3 ) 7.26 δ): 6.02 (ddd, Jcis ) 9.9 Hz, J ) 5.7 Hz,
4J ) 2.1 Hz, 1H), 5.75 (m, 1H), 5.26 (unres m, 1H), 1.99 (s, 3H),
1.22-2.13 (m, 5H), 0.83 (s, 9H). 13C + APT (75 MHz, CDCl3 ) 77.00
δ): 170.52 (up, -CO2Me), 134.15 (down, CHd), 123.78 (down, CHd),
67.71 (down, CH-O), 38.30 (down, CH), 31.65 (up, C of tBu), 29.45
(up, CH2), 26.98 (down, CH3), 26.72 (up, CH2), 21.27 (down, CH).
1
in a pressure/vacuum NMR tube at 180 °C for 5 h. H NMR (300
MHz, C6D6, C6D5H ) 7.16 δ): δ ) 9.40 (t, J ) 2.0 Hz, 1H), 5.61 (m,
1H), 5.38 (d of unres m, 1H), 2.47 (m, 1H), 2.92 (d of t, 1H), 1.82 (m,
1H), 1.67 (m, 1H), 1.57 (m, 1H), 1.23 (dd of t, 1H), 0.75 (s, 9H).
13C + APT (75 MHz, C6D6, C6D6 ) 128.39 δ): δ ) 200.87 (down,
CHO), 130.56 (down, CHd), 128.60 (down, CHd), 50.74 (up, CH2),
44.63 (down, CH), 32.87 (down), 32.55 (up), 31.86 (up), 29.34 (down),
27.55 (down, Me), 27.34 (up). IR (neat): 3025, 2965, 2925, 2890, 2875,
2725, 1735. MS (high res EI): calcd for C12H20O 180.1514, found
180.1509.
trans-5-tert-Butylcyclohex-2-enyl 1-Methylvinyl Ether (4). trans-
5-tert-Butylcyclohex-2-enyl acetate (28) (400 mg, 2.04 mmol) in 3 mL
of anhydrous THF was mixed with Tebbe reagent (5 mL, 0.5 M in
toluene, Aldrich) at -78 °C under argon atmosphere. The cold bath
was removed and kept at room temperature for 30 min. Workup
followed that for 1. Kugelrohr distillation from Na2CO3 gave 214 mg
2-Cyclohexenyl Vinyl Ether (6).78 The compound was prepared
from 2-cyclohexenol (800 mg), ethyl vinyl ether (17 mL), and Hg-
(OAc)2 (2 × 60 mg) by the same procedure as described above for 3
1
of pale yellow oil. H NMR (300 MHz, CDCl3, CHCl3 ) 7.26 ppm):
4
3
3
6.04 (ddd, J ) 1.8 Hz, J ) 5.4 Hz, Jcis ) 9.6 Hz, 1H; ring CHd),
5.84 (m, 1H; ring CHd), 4.52 (br s, 1H; CH-O), 3.91 (s, 2H, CH2d),
1
and 5. H NMR (300 MHz, C6D6, C6D5H ) 7.16 δ): δ ) 6.28 (dd,
3
1H, J ) 6.9, 14.4 Hz), 5.78 (m, 1H), 5.66 (m, 1H), 4.38 (dd, Jtrans
)
2
3
14.4 Hz, J ) 1.5 Hz, 1H), 4.12 (unres m, 1H), 4.01 (dd, Jcis ) 6.6
(114) Watanabe, W. H.; Conlon, L. E. J. Am. Chem. Soc. 1957, 79, 2828.
(115) Agosta, W. C.; Wolff, S. J. Am. Chem. Soc. 1976, 98, 4182-
4188.
Hz, J ) 1.5 Hz, 1H), 1.53-1.75 (m, 5H), 1.27 (m, 1H). 13C + APT
2
(75 MHz, C6D6, C6D6 ) 128.39 δ): δ ) 151.34 (down, O-CHd),