Synthesis of Chiral Cyclohexenones from α-Campholenic, Fencholenic, and β-Campholenic Derivatives

Article abstract of DOI:10.1007/s00706-003-0040-2

Optically active dimethylcyclohexenones, potential building blocks for enantioselective syntheses of various naturally active substances, were prepared. These compounds were obtained by oxidation with KMnO ₄/Pb(OAc)₄ or ozonolysis of the corresponding cyclopentenic precursors, followed by aldol condensation. During the course of the preparation intermediate diols and chiral polyfunctional carbonyl derivatives were separated and identified analytically.

Full text of DOI:10.1007/s00706-003-0040-2

Monatshefte f€ur Chemie 134, 1593–1606 (2003)
DOI 10.1007/s00706-003-0040-2
Synthesis of Chiral Cyclohexenones
from a-Campholenic, Fencholenic,
and b-Campholenic Derivatives
ꢀ
Katrin Anhalt, Ines Sprung, and Klaus Schulze
€
Institut f€ur Organische Chemie, Universitat Leipzig, D-04103 Leipzig, Germany
Received February 10, 2003; accepted February 17, 2003
Published online October 9, 2003 # Springer-Verlag 2003
Summary. Optically active dimethylcyclohexenones, potential building blocks for enantioselective
syntheses of various naturally active substances, were prepared. These compounds were obtained by
oxidation with KMnO4=Pb(OAc)4 or ozonolysis of the corresponding cyclopentenic precursors, fol-
lowed by aldol condensation. During the course of the preparation intermediate diols and chiral
polyfunctional carbonyl derivatives were separated and identified analytically.
Keywords. Aldol condensation; Cyclohexenones; Oxidation; Ozonolysis; Terpenoids.
Introduction
ꢀ-Pinene (1a) and ꢀ-ethylapopinene (1b), which are both available in enantiomeric
pure forms [1], are becoming more widely used in total syntheses of complex
chiral, biologically active products [2]. Little is known about the use of ꢀ-cam-
pholenic and fencholenic derivatives, which are obtainable from ꢀ-pinene oxide
(2a) by camphane-[3, 4] or fenchane-rearrangement [5] via trans-pinocarveol (4)
and bromoisofenchol (5). The cyclopentenes of type 3 and 6 possess a stereogenic
centre resulting from the C-5-centre of ꢀ-pinene.
The ꢁ-campholenic system 8 bears chiral information resulting from
trans-epoxy-ꢀ-campholenic products of type 7 via the Nametkin rearrangement
[6].
We herein report the preparation of chiral cyclohexenones 12, 16, and 21 from
ꢀ-pinene. They may be suitable starting materials for natural compounds as, e.g.
taxols [7], strigol [8], carotenoids [9], and fragrances [3, 10]. Enantiomeric
excesses of the cyclohexenones correspond to the ee of the starting materials
a-pinene or nopol.
ꢀ
Corresponding author. E-mail: kschulze@organik.chemie.uni-leipzig.de

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K. Anhalt et al.
Scheme 1. i) AcOOH, CH2Cl2, 40ꢁC; ii) ZnBr2, toluene, reflux; iii) Al(OiPr)3, toluene, reflux; iv)
HBr, pentane, ꢂ20ꢁC; v) AgNO3, t-BuOH=H2O
Scheme 2
Scheme 3
Results and Discussion
We first performed the oxidation of ꢀ-campholenic derivatives 9a–9d with KMnO4
and obtained mixtures of diols as well as other oxidized products. On treatment
with Pb(OAc)4 the diol mixture led to either mixtures of 11 and 12 or pure cyclo-
hexenone (in the case of 12a). Refluxing with p-toluenesulfonic acid completed the
aldol condensation to give 12b–12d. An alternative route to cyclohexenone 12c [3]
involved ozonolysis followed by aldol cyclization. The overall yields, e.g. in the
case of 12c, were 53% via i)–iii) and 36% via iv).

Synthesis of Chiral Cyclohexenones
1595
Scheme 4. i) KMnO4=MgSO4, H2O=EtOH, 0–10ꢁC; ii) Pb(OAc)4, toluene, reflux; iii) p-TsOH,
toluene, reflux; iv) a) O3, CH2Cl2=MeOH, ꢂ40ꢁC; b) Zn=CH3COOH, Et2O, reflux; c) iii)
For preparation of dimethylcyclohexenones 16a and 16b from fencholenic
derivatives we employed the methodology described above. Again, a mixture of
diols 14a and 14b and aliphatic ketoaldehydes 15a and 15b was isolated after
conversion with KMnO4. This mixture could be transformed into the desired prod-
ucts 16a and 16b by oxidation and cyclization in 18 and 34% overall yields.
Alternatively, 16b was obtained after ozonolysis and aldol condensation in 44%
overall yield.
ꢁ-Campholenic derivatives 8 were accessible by Nametkin rearrangement of
trans-epoxy-ꢀ-campholenic derivatives [6] and protection of the formed secondary
Scheme 5. i) KMnO4=MgSO4, H2O=EtOH, 0–10ꢁC; ii) Pb(OAc)4, toluene, reflux; iii) p-TsOH,
toluene, reflux; iv) a) O3, CH2Cl2=MeOH, ꢂ40ꢁC; b) Zn=CH3COOH, Et2O, reflux; c) iii)

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K. Anhalt et al.
Scheme 6. i) KMnO4=MgSO4, H2O=EtOH, reflux
Scheme 7. i) KMnO4=MgSO4, H2O=EtOH, 0–10ꢁC; ii) a) Pb(OAc)4, toluene, reflux; b) p-TsOH,
toluene, reflux
Scheme 8. i) a) O3, CH2Cl2=MeOH, ꢂ40ꢁC; b) Zn=CH3COOH, Et2O, reflux; ii) KMnO4=MgSO4,
H2O=EtOH, 0–10ꢁC; iii) p-TsOH, toluene, reflux; iv) KOH, EtOH

Synthesis of Chiral Cyclohexenones
1597
alcohol. Oxidation of derivative 8a gave exclusively ꢀ,ꢁ-unsaturated carbonyl com-
pounds 17 and 18 lacking the desired asymmetric centre of the starting material. The
oxidation of 8b with KMnO4 led to a mixture of diol 19a and diketone 20a. Major
difficulties occured in the intramolecular cyclization of diketone 20a. The main
products were aliphatic ꢀ,ꢁ-unsaturated diketone 17 in addition to cyclohexane-
dienone 22, but only 14% of the substituted cyclohexenone 21a was obtained.
Oxidation of 8c with KMnO4 led also to a diol=diketone mixture. Ozonolysis
gave exclusively 20b. Cyclization of 20b with p-toluenesulfonic acid gave 11% of
the desired product 21b. Treatment of 20b with base yielded only the 3,4,4-tri-
methylcyclohexa-2,5-dienones 25a and 25b.
The stereochemistry of the diols 10, 14, and 19 was analysed by NOE-NMR
experiments. We obtained diols in which both hydroxyl groups are in a trans-
position with respect to the sidechain. The above-mentioned ozonolyses of 9c,
13b, and 8c always gave exceptionally stable ozonides. It was not possible to
completely reduce the obtained secondary ozonides, neither with Me2S [3] nor
with reagents like P(Ph)3 or Na2SO3. We will discuss the isolated ozonide diaste-
reomers as well as the influence of the methyl substituents on the reactivity of the
ozonides in a forthcoming publication.
Experimental
NMR spectra were recorded on a Varian Gemini 200 or Gemini 2000 (1H NMR: 200 MHz, 13C
NMR: 50.3MHz), a Gemini 300 (1H NMR: 300 MHz, 13C NMR: 75.7 MHz) or Unity 400
(1H NMR: 400 MHz, 13C NMR: 100.6 MHz) spectrometer in CDCl3. IR spectra of neat samples
were obtained using a Carl-Zeiss-Jena Specord M 80 IR spectrophotometer or ATI Mattson, Genesis
Series FT-IR spectrophotometer. Mass spectra were measured with a Masslab VG 12250 (column
SGE 25QC2=BPX5 25 m ꢃ 0.22 mm ꢃ 0.25ꢂm) or a Hewlett-Packard HP 5890-II=5972 Series (col-
umn HP5 30 m ꢃ 0.32 mm ꢃ 0.25ꢂm). GLC were recorded on a Hewlett-Packard HP 5890-II (oven
temperature is always written in brackets) equipped with a flame ionisation detector, capillary
column: HP1 (25 m ꢃ 0.2 mm ꢃ 0.33ꢂm) and for determination of ee: Lipodex E, Macherey-Nagel
(modified ꢃ-cyclodextrin), 25 m ꢃ 0.25 mm). The silica gel used in column chromatography was
from Merck KG 60 (230–400 mesh ASTM) and the pump from Optima (Model 10007). Distillations
€
were done partially with a Buchi ball tube distillation instrument GKR 51, bp corresponds to air
temperature. Ozone was produced with a Fischer ozone generator OZ 500 (output: 100 scale marks,
O2-stream: 40 dm3=h). (1S)-(–)-ꢀ-Pinene (1a) (81% ee) was purchased from Merck and (1R)-(–)-
nopol (91% ee) (1b) from Aldrich. Compound 3a was prepared as reported [4a], 3b [4c] and 6 were
described [4b], 8a was prepared as reported [5b].
General Procedures
I Oxidation with KMnO4: To a well stirred ice-cooled soln. of 0.10mol of the respective olefin in
200 cm3 of ethanol was added dropwise a suspension of 0.10mol of KMnO4 and 0.08mol of MgSO4 in
250 cm3 of H2O so that the reaction temperature was about 5–10ꢁC. After that the mixture was stirred
at rt about 2 h and the conversion was monitored by GLC. If necessary, KMnO4 and MgSO4 were
added again and the mixture was stirred until no educt was detected. Then MnO2 was removed by
filtration and the residue was washed with copious amounts of acetone. The combined filtrates were
concentrated to about 100 cm3, NaCl was added and the soln. was extracted with CHCl3. The com-
bined org. layers were dried (Na2SO4) and the solvent was removed in vacuo. The resulting crude oil
was purified by column chromatography, distillation, or used immediately for the next reaction step.

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K. Anhalt et al.
II Reaction of diols with Pb(OAc)4: To a stirred soln. of 10mmol of Pb(OAc)4 in 5 cm3 of dry toluene
was added at rt 10 mmol of the diol and the mixture was refluxed (0.5–15h) until no educt was
detected by GLC. Then it was filtered and the residue was thoroughly washed with toluene. After that
the combined org. layers were evaporated. The crude oil was purified by column chromatography,
distillation, or used immediately for the next reaction step.
III Reaction of dicarbonyl compounds with p-toluenesulfonic acid: To a soln. of 10mmol of the
dicarbonyl compound in 20 cm3 of dry toluene a spatula tip of p-toluenesulfonic acid was added
and refluxed (ca. 0.5–3 h) until no educt was monitored by GLC. The cooled reaction mixture was
washed with H2O, dried (Na2SO4), and concentrated. The crude oil was purified by distillation or
column chromatography.
IV Ozonolysis of cyclopentenic double bonds: 1 mmol of olefin was diluted in 21 cm3 of dry CH2Cl2
and 25 cm3 of methanol and cooled to ꢂ40ꢁC. A flow of O3 was passed through until the soln. became
blue and no starting material was detected by TLC. The apparatus was purged with O2 and N2. The
solvent was evaporated and the residue either purified by column chromatography or used without
purification for the next reaction.
V Decomposition of ozonides with Zn=acetic acid: To a stirred soln. of 1 mmol of the crude product
from ozonolysis in 15 cm3 of diethyl ether was added at rt 3 g of Zn-powder and 2 cm3 of acetic acid.
The reaction mixture was refluxed until no ozonide was detected by TLC. The precipitate was filtered
off and washed with diethyl ether. The combined org. layers were washed with H2O and saturated
NaHCO3 solution, dried (Na2SO4), and concentrated. The crude product was purified by distillation or
column chromatography.
2-[(4-Methoxy-2,3,3-trimethylcyclopent-1-enyl)methyl]-1,3-dioxolane (8b, C13H22O3)
To a well stirred suspension of 28 mmol of NaH in 10 cm3 of dry n-hexane at rt 4.30 g of 2-[(4-
hydroxy-2,3,3-trimethylcyclopent-l-enyl)methyl]-1,3-dioxolane [5b] (20.3 mmol) in 10cm3 of dry n-
hexane were added dropwise. After that the mixture was refluxed for 3 h and to the cooled reaction
mixture 3.3 cm3 of MeI (52 mmol) were added at rt. After one night at rt the mixture was stirred at
40ꢁC (ca. 10 h) until no educt was detected by GLC. The reaction mixture was cooled to 0ꢁC and ice
H2O was added. The aqueous layer was further extracted with n-hexane and the combined org. layers
were washed with H2O and brine, dried (Na2SO4), and then concentrated to give 79% of crude 8b.
Ball tube distillation gave 1.90 g (41%) of a colourless liquid. Bp0.9 110ꢁC; GLC (180ꢁC): 88%; IR:
ꢄꢀ¼ 2822 (CH3–O), 1648 (>C¼C<), 1127, 1099, 1038 (C–O–C) cmꢂ1; MS: m=z ¼ 227 (<1,
Mþ þ H), 226 (<1, Mþ), 225 (<1, Mþ ꢂ H), 194 (4, Mþ-CH4O), 182 (<1, Mþ-C2H4O), 107 (2),
1
0
0
0
91 (5), 73 (100); H NMR (200 MHz, CDCl3): ꢅ ¼ 0.89 (s, 3 -CH3 ), 1.00 (s, 3 -CH3) 1.50
(t, J ¼ 2.0 Hz, 20-CH3), 2.21 (m, 1H, 50-CH2), 2.37 (d, J ¼ 4.8 Hz, CH2), 2.52 (ddm, J ¼ 15.3, 6.8Hz,
1H, 50-CH2), 3.44 (s, CH3–O), 3.46 (t, J ¼ 6.8 Hz, 40-CH), 3.81 (m, 4-CH2), 3.94 (m, 5-CH2) 4.85
(t, J ¼ 4.8 Hz, 2-CH) ppm; 13C NMR (50.3 MHz, CDCl3): ꢅ ¼ 10.13 (20-CH3), 19.33=25.95 (30-CH3),
34.21 (CH2), 39.26 (50-CH2), 49.11 (30-C), 58.14 (CH3–O), 65.28 (4-CH2, 5-CH2), 89.20 (40-CH),
104.36 (2-CH), 125.29 (10-C), 141.46 (20-C) ppm.
Methyl[2-(4-ethoxy-2,3,3-trimethylcyclopent-1-enyl)ethyl]ether (8c, C13H24O2)
Methyl[2-(4-hydroxy-2,3,3-trimethylcyclopent-1-enyl)ethyl]ether: 13.76 g of trans-Epoxy-ꢀ-cam-
pholene methylether (0.075 mol) gave as reported in Ref. [5b] 17.3g of the trimethylcyclopentanol
derivative. 2.00 g of this crude product were purified for analytical identification by ball tube distilla-
tion to give 1.40 g (88%) of a colourless liquid. Bp2.5 105ꢁC; GLC (120ꢁC): 92%; IR: ꢄꢀ¼ 3426 (–OH),
1646 (>C¼C<), 1116 (C–O–C) cmꢂ1; MS: m=z ¼ 184 (<1, Mþ), 166 (25, Mþ-H2O), 151 (2, Mþ-
1
H2O, –CH3), 137 (20), 121 (93), 108 (72), 95 (21), 79 (23), 45 (100); H NMR (200MHz, CDCl3):

Synthesis of Chiral Cyclohexenones
1599
ꢅ ¼ 0.92 (s, 30-CH3), 0.94 (s, 30-CH3), 1.51 (t, J ¼ 2.0 Hz, 20-CH3), 1.82 (bs, OH), 2.13 (dm,
J ¼ 15.7Hz, 1H, 50-CH2), 2.30 (dt, J ¼ 3.2, 7.1 Hz, 2-CH2), 2.53 (ddm, J ¼ 15.7, 6.6 Hz, 1H,
50-CH2), 3.31 (s, CH3–O), 3.67 (t, J ¼ 7.1 Hz, 1-CH2), 3.84 (t, J ¼ 6.0 Hz, 40-CH) ppm; 13C NMR
(50.3MHz, CDCl3): ꢅ ¼ 10.13 (20-CH3), 19.15=25.00 (30-CH3), 29.40 (2-CH2), 42.16 (50-CH2), 49.79
(30-C), 58.93 (CH3–O), 71.59 (1-CH2), 80.12 (40-CH), 127.68 (10-C), 139.64 (20-C) ppm.
Methyl[2-(4-ethoxy-2,3,3-trimethylcyclopent-1-enyl)ethyl]ether (8c): To a well stirred suspension of
166 mmol of NaH in 50 cm3 of dry cyclohexane at rt 12.90 g of methyl[2-(4-hydroxy-2,3,3-trimethyl-
cyclopent-l-enyl)ethyl]ether (70 mmol) were dropped. After that the mixture was stirred at rt for 3 h and
13.2cm3 of EtI (164mmol) in 30 cm3 of dry cyclohexane were added. After 2 h at rt the mixture was
refluxed (about 7 h) until only 2% of educt was detected by GLC. The reaction mixture was cooled to
0ꢁC and ice H2O was added. The aqueous layer was extracted with cyclohexane and the combined org.
layers were washed with H2O and brine, dried (Na2SO4), and then concentrated. The crude product
contained 87% 8c. Distillation gave 8.1 g (55%) of a colourless liquid. Bp2.2 75–77ꢁC; n2D0: 1.4556; GLC
(120ꢁC): 95%; IR: ꢄꢀ¼ 2807 (CH3–O), 1648 (>C¼C<), 1119, 1104 (C–O–C) cmꢂ1; MS: m=z ¼ 212
(4, Mþ), 211 (3, Mþ ꢂ H), 197 (18, Mþ-CH3), 166 (52, Mþ-C2H6O), 151 (8), 137 (20), 121 (100), 108
(75); 1H NMR (200MHz, CDCl3): ꢅ ¼ 0.88 (s, 30-CH3), 0.98 (s, 30-CH3), 1.17 (t, J ¼ 6.8 Hz, CH3–CH2–
O), 1.48 (t, J ¼ 2.0 Hz, 20-CH3), 2.16 (ddm, J ¼ 15.3, 6.5 Hz, 1H, 50-CH2), 2.28 (t, J ¼ 7.2 Hz, 2-CH2),
2.40 (ddm, J ¼ 15.3, 7.0 Hz, 1H, 50-CH2), 3.30 (s, CH3–O), 3.34 (t, J ¼ 7.2 Hz, 1-CH2), 3.49 (q,
13
J ¼ 6.8 Hz, CH3–CH2–O), 3.52 (m, 40-CH) ppm; C NMR (50.3 MHz, CDCl3): ꢅ ¼ 9.85 (20-CH3),
15.94 (CH3–CH2–O), 19.41=26.00 (30-CH3), 29.50 (2-CH2), 39.21 (50-CH2), 49.10 (30-C), 58.89 (CH3–
O), 65.84 (CH3–CH2–O), 71.66 (1-CH2), 87.31 (40-CH), 127.30 (10-C), 140.05 (20-C) ppm.
5-(2-Acetoxyethyl)-6,6-dimethylcyclohex-2-enone (12a, C12H18O3)
a) Reaction of ꢀ-campholene acetate (9a) with KMnO4: According to procedure I 15.5g of ꢀ-
campholene acetate [3] (0.079 mol) gave 23.0 g (74%) of a crude product which contained 59% 10a
and 27% 12a. For analytical use, ball tube distillation of a small amount was performed. t-4-(2-
Acetoxyethyl)-1,5,5-trimethylcyclopentane-R-1,c-2-diol (10a): Bp 185ꢁC; GLC (180ꢁC): 84%; IR:
ꢄꢀ¼ 3450 (–OH), 1740 (C¼O), 1240, 1040 (C–O–C) cmꢂ1; MS: m=z ¼ 188 (1, Mþ-C2H2O), 170
1
(80, Mþ-C2H2O, –H2O), 152 (1), 143 (1), 137 (5), 127 (5), 109 (55), 83 (45), 44 (100); H NMR
(200 MHz, CDCl3): ꢅ ¼ 0.66 (s, 5-CH3), 0.89 (s, 5-CH3), 1.07 (s, 1-CH3), 1.10–2.50 (m, 4-CH, 3-CH2,
10-CH2), 2.00 (s, C(O)–CH3), 3.95 (m, 2-CH, 20-CH2) ppm; 13C NMR (50.3 MHz, CDCl3):
ꢅ ¼ 19.48=20.40 (5-CH3), 20.10 (1-CH3), 21.45 (C(O)–CH3), 30.03 (10-CH2), 37.87 (3-CH2), 42.03
(4-CH), 46.61 (5-C), 64.72 (20-CH2), 76.90 (2-CH), 82.14 (1-C), 171.72 (C¼O) ppm.
b) Reaction of the crude product of a) with Pb(OAc)4: According to procedure II 23.00 g of the mixture
of 10a and 12a gave after distillation 6.43g (39% via a) and b)) of the colourless oil 12a; analytical
data see Ref. [3].
5-(2-Benzyloxyethyl)-6,6-dimethylcyclohex-2-enone (12b, C17H22O2)
a) Reaction of ꢀ-campholene benzylether (9b) with KMnO4: According to procedure I 5.19 g of ꢀ-
campholene benzylether [11] (9b) (21 mmol) and 5.11 g of KMnO4 gave after distillation 2.15g (31%)
of a mixture which contained 57% 10b and 30% secondary products.
t-4-(2-Benzyloxyethyl)-1,5,5-trimethylcyclopentane-R-1,c-2-diol (10b): Bp0.7 135ꢁC; GLC
(180ꢁC): 96%; MS: m=z ¼ 278 (<1, Mþ), 260 (<1, Mþ-H2O), 259 (<1), 246 (Mþ-CH4O), 205
(<1), 185 (3), 170 (23), 152 (8), 123 (15), 105 (46), 91 (100); 1H NMR (200MHz, CDCl3): ꢅ ¼ 0.68
(s, 5-CH3), 0.95 (s, 5-CH3), 1.13 (bs, 1-CH3), 1.20–2.50 (m, 4-CH, 3-CH2, 10-CH2), 3.36 (m, 20-CH2),
4.05 (m, 2-CH), 4.50 (s, CH2–Carom), 7.26–7.35 (m, 5H, CHarom) ppm; 13C NMR (50.3 MHz, CDCl3):
ꢅ ¼ 19.61=20.21=20.62 (1-CH3, 5-CH3), 31.19 (10-CH2), 38.21 (3-CH2), 42.13 (4-CH), 47.95 (5-C),
70.60 (20-CH2), 73.50 (CH2–Carom), 77.20 (2-CH), 82.43 (1-C), 128.02=128.16=128.85 (CHarom),
138.97 (Carom) ppm.

1600
K. Anhalt et al.
b) Reaction of the mixture from a) with Pb(OAc)4: According to procedure II 2.1 g of the mixture of
10b and secondary oxidized products gave 2.1g of a liquid, which contained 55% 11b and 40% 12b. It
was not possible to separate the products neither by distillation nor by column chromatography. GLC
(200ꢁC): 94% 11b and 12b, GLC (Chrompack CP-Chiral-Dex CB, 200ꢁC): 55% 11b and 40% 12b. 3-
(2-Benzyloxyethyl)-4,4-dimethyl-5-oxohexanal (11b): MS: m=z ¼ 276 (<1, Mþ), 261 (<1, Mþ-CH3),
243 (4, Mþ-CH3, –H2O), 169 (6), 127 (4), 107 (10), 91 (100); 1H NMR (200 MHz, CDCl3) (simulta-
neously with 12b): ꢅ ¼ 1.04 (s, 4-CH3), 1.07 (s, 4-CH3), 1.30–2.60 (m, 3-CH, 10-CH2, 2-CH2), 2.15
(s, 6-CH3), 3.43 (m, 20-CH2), 4.40 (s, CH2–Carom), 7.28–7.33 (m, 5H, CHarom), 9.67 (bs, CHO) ppm;
13C NMR (50.3MHz, CDCl3) (simultaneously with 12b): ꢅ ¼ 21.03=21.63 (4-CH3), 25.40 (6-CH3),
31.59 (10-CH2), 35.29 (3-CH), 45.78 (2-CH2), 51.17 (4-C), 68.62 (20-CH2), 73.01 (CH2–Carom),
127.65=128.12=128.25 (CHarom), 138.14 (Carom), 201.56 (CHO), 213.59 (5-C¼O) ppm.
c) Reaction of the mixture from b) with p-toluenesulfonic acid: According to procedure III 1.80g of the
11b=12b mixture yielded after ball tube distillation 1.11 g (67%) of the liquid oil 12b. Bp1.2 195ꢁC;
GLC (Chrompack CP-Chiral-Dex CB, 200ꢁC): 94%; IR: ꢄꢀ¼ 3063 (–C¼CH), 3031 (–CHarom), 1672
(C¼O), 1104 (s, C–O–C), 739, 698 (m, –CHarom) cmꢂ1; MS: m=z ¼ 258 (<1, Mþ), 167 (2, Mþ-
C7H7), 152 (20, Mþ-C7H7, –CH3), 149 (5), 123 (2), 107 (15), 91 (100); 1H NMR (200MHz, CDCl3):
ꢅ ¼ 0.98 (s, 6-CH3), 1.16 (s, 6-CH3), 1.47 (m, 1H, 10-CH2), 1.91 (m, 1H, 10-CH2), 1.98 (m, 5-CH), 2.00
(m, 1H, 4-CH2), 2.43 (m, 1H, 4-CH2), 3.51 (m, 20-CH2), 4.49 (d, J ¼ 2.6 Hz, CH2–Carom), 5.93 (td,
J ¼ 10.2, 1.8 Hz, 2-CH), 6.80 (m, 3-CH), 7.30–7.35 (m, 5H, CHarom) ppm; 13C NMR (50.3MHz,
CDCl3): ꢅ ¼ 19.31=22.68 (6-CH3), 29.17 (4-CH2), 29.70 (10-CH2), 41.00 (5-CH), 45.64 (6-C), 68.99
(20-CH2), 73.42 (CH2–Carom), 128.14=128.93= 138.82 (CHarom, Carom), 128.57 (2-CH), 147.94 (3-CH),
205.34 (1-C¼O) ppm.
5-(2-Methoxyethyl)-6,6-dimethylcyclohex-2-enone (12c, C11H18O2)
a) Reaction of ꢀ-campholene methylether (9c) with KMnO4: According to procedure I 7.72 g of ꢀ-
campholene methylether (46 mmol) yielded a crude oil which contained 23% 9c, 40% 10c, and 24%
11c. Ball tube distillation yielded for analytical identification pure diol. t-4-(2-Methoxyethyl)-1,5,5-
trimethylcyclopentane-R-1,c-2-diol (10c): Bp0.36 125ꢁC; GLC (150ꢁC): 92%; IR: ꢄꢀ¼ 3418 (–OH),
2829 (CH3–O), 1116, 1089, 1065 (C–O–C) cmꢂ1; MS: m=z ¼ 202 (1, Mþ), 170 (100, Mþ-CH4O), 152
1
(1), 137 (5), 127 (8), 109 (30), 83 (25); H NMR (200 MHz, CDCl3): ꢅ ¼ 0.66 (s, 5-CH3), 0.93 (s, 5-
CH3), 1.12 (s, 1-CH3), 1.26 (m, 1H, 10-CH2), 1.62 (m, 1H, 10-CH2), 1.69 (m, 1H, 3-CH2), 1.72 (m, 1H,
3-CH2), 2.12 (m, 4-CH), 2.32 (bs, OH), 2.63 (bs, OH), 3.31 (s, CH3–O), 3.36 (m, 20-CH2), 4.00 (m, 2-
13
CH) ppm; C NMR (50.3 MHz, CDCl3): ꢅ ¼ 19.54=20.43 (5-CH3), 20.18 (1-CH3), 30.98 (10-CH2),
38.11 (3-CH2), 41.93 (4-CH), 46.61 (5-C), 59.03 (CH3–O), 72.87 (20-CH2), 77.10 (2-CH), 82.37 (1-C)
ppm.
b) Reaction of the mixture from a) with Pb(OAc)4 and p-toluenesulfonic acid: According to procedure
II 3.20g of a mixture of 10c and 11c (16 mmol) gave a crude product (13% 11c and 63% 12c), which
was used without further purification for procedure III. Ball tube distillation yielded 2.69g (92%) of
the colourless oil 12c. Bp0.4 85ꢁC; GLC (150ꢁC): 92%; IR: ꢄꢀ¼ 3033, 821 (–C¼CH), 2829 (CH3–O),
1677 (C¼O), 1117 (C–O–C) cmꢂ1; MS: m=z ¼ 183 (1, Mþ þ H), 182 (8, Mþ), 167 (2, Mþ-CH3), 154
(2), 150 (16), 135 (18), 123 (15), 82 (35), 68 (100); 1H NMR (200MHz, CDCl3): ꢅ ¼ 0.96 (s, 6-CH3),
1.13 (s, 6-CH3), 1.40 (m, 1H, 10-CH2), 1.83 (m, 1H, 10-CH2), 1.93 (m, 5-CH), 2.11 (m, 1H, 4-CH2),
2.48 (m, 1H, 4-CH2), 3.29 (s, CH3–O), 3.37 (d, J ¼ 5.6 Hz, 1H, 20-CH2), 3.41 (d, J ¼ 5.6 Hz , 1H, 20-
CH2), 5.90 (td, J ¼ 10.9, 1.9Hz, 2-CH), 6.80 (m, 3-CH) ppm; 13C NMR (50.3 MHz, CDCl3):
ꢅ ¼ 19.37=22.76 (6-CH3), 29.24 (4-CH2), 29.64 (10-CH2), 41.05 (5-CH), 45.65 (2-C), 59.03 (CH3–
O), 71.49 (20-CH2), 128.54 (2-CH), 147.71 (3-CH), 205.01 (1-C¼O) ppm.
c) Ozonolyses of ꢀ-campholene methylether (9c), decomposition of the ozonide, and cyclisation with p-
toluenesulfonic acid: According to procedures I, II, and III 2.76g of ꢀ-campholene methylether [12]

Synthesis of Chiral Cyclohexenones
1601
(16.4mmol) yielded without purification of the intermediate products after final ball tube distillation
1.06g (36%) of cyclohexenone 12c.
d) Ozonolyses of ꢀ-campholene methylether (9c) and decomposition of the ozonide: According to
procedures I and II 1.84 g of ꢀ-campholene methylether [12] (10.9 mmol) yielded after ball tube
distillation 0.76 g (35%) of the colourless oil 3-(2-methoxyethyl)-4,4-dimethyl-5-oxohexanal (11c):
Bp0.95 100ꢁC; GLC (180ꢁC): 86%; IR: ꢄꢀ¼ 2833 (CH3–O), 1726, 1704 (C¼O), 1118 (C–O–C)
cmꢂ1; MS: m=z ¼ 200 (<1, Mþ), 167 (1, Mþ-CH3, –H2O), 157 (5, Mþ-CH3CO), 139 (1), 125
1
(15), 107 (30), 86 (42), 43 (100); H NMR (200 MHz, CDCl3): ꢅ ¼ 1.02 (s, 4-CH3), 1.05 (s, 4-
CH3), 1.34 (m, 1H, 20-CH2), 1.60 (m, 1H, 20-CH2), 2.13 (s, 6-CH3), 2.31 (m, 1H, 2-CH2), 2.61 (m,
1H, 2-CH2), 2.34 (m, 3-CH), 3.21 (s, CH3–O), 3.29 (t, J ¼ 6.1 Hz, 10-CH2), 9.69 (t, J ¼ 1.8 Hz, 1-CHO)
13
ppm; C NMR (50.3 MHz, CDCl3): ꢅ ¼ 21.49=21.99 (4-CH3), 25.80 (6-CH3), 31.81 (20-CH2), 35.75
(3-CH), 46.19 (2-CH2), 51.55 (4-C), 58.89 (CH3–O), 71.30 (10-CH2), 201.95 (1-CHO), 213.89
(5-C¼O) ppm.
5-(2-Acetoxyethyl)-2,6,6-trimethylcyclohex-2-enone (12d, C13H20O3)
a) Reaction of ethyl-ꢀ-campholene acetate (9d) with KMnO4: According to procedure I (but rt during
KMnO4 addition) 1.84g of ethyl-ꢀ-campholene acetate [3] (9d) (8.7mmol) yielded 1.44g (62%
relating to 10d) of a liquid which contained 74% 10d and 13% 11d. t-4-(2-Acetoxyethyl)-1-ethyl-
5,5-dimethylcyclopentane-R-1,c-2-diol (10d): GLC (180ꢁC): 74%; MS: m=z ¼ 244 (3, Mþ), 226 (2,
Mþ-H2O), 207 (2), 184 (20, Mþ-CH3COOH), 166 (8), 151 (5), 141 (17), 123 (42), 82 (62), 43 (100);
1H NMR (200 MHz, CDCl3): ꢅ ¼ 0.66 (s, 5-CH3), 0.95 (s, 5-CH3), 0.98 (t, CH3–CH2), 1.00–2.60 (m,
4-CH, 3-CH2, 10-CH2), 1.54 (t, J ¼ 7.5 Hz, CH2–CH3), 2.04 (s, C(O)–CH3), 4.40 (m, 2-CH, 20-CH2)
ppm; 13C NMR (50.3 MHz, CDCl3): ꢅ ¼ 8.51 (CH3–CH2), 18.84=20.90 (5-CH3), 21.52 (C(O)–CH3),
27.71 (CH2–CH3), 29.66 (10-CH2), 39.03 (3-CH2), 42.38 (4-CH), 47.70 (5-C), 64.71 (20-CH2), 76.82
(2-CH), 83.07 (1-C), 171.74 (C¼O) ppm.
b) Reaction of the mixture from a) with Pb(OAc)4: According to procedure II 1.20g (3.64 mmol of 10d
and 0.65 mmol of 11d) yielded after ball tube distillation 0.30g (29%) of the colourless oil 3-(2-
acetoxyethyl)-4,4-dimethyl-5-oxoheptanal (11d). Bp0.85 175ꢁC; GLC (80ꢁC): 72%; MS: m=z ¼ 242 (4,
Mþ), 224 (5, Mþ-H2O), 198 (3, Mþ-C2H4O), 182 (4, Mþ-CH3COOH), 164 (2), 138 (30), 121 (20), 95
1
(43), 83 (100); H NMR (200 MHz, CDCl3): ꢅ ¼ 0.98 (t, 7-CH3), 0.99 (s, 4-CH3), 1.05 (s, 4-CH3),
1.20–1.80 (m, 10-CH2), 2.00 (s, CH3–C(O)), 2.00–2.70 (m, 3-CH, 6-CH2, 2-CH2), 3.99 (m, 20-CH2),
9.71 (bs, 1-CHO) ppm; 13C NMR (50.3 MHz, CDCl3): ꢅ ¼ 8.48 (7-CH3), 21.32=21.76=22.10 (4-CH3,
CH3–C(O)–), 30.87=30.95 (10-CH2, 6-CH2), 35.16 (3-CH), 46.29 (2-CH2), 51.17 (4-C), 63.32 (20-
CH2), 171.41 (C¼O), 213.89 (5-C¼O), 201.71 (1-CHO) ppm.
c) Reaction of 11d with p-toluenesulfonic acid: According to procedure III 144 mg of 11d (5.95 mmol)
yielded after ball tube distillation 54mg (41%) of the colourless liquid 12d (analytical data see Ref.
[3]).
5-(2-Acetoxyethyl)-4,4-dimethylcyclohex-2-enone (16a, C12H18O3)
a) Reaction of fencholene acetate (13a) with KMnO4: According to general procedure I 5.7 g of
fencholene acetate [13] (28.6 mmol) gave with 10g of KMnO4 a crude product (8.0g, 46% relating
to 14a and 37% to 15a) which contained 38% 14a and 31% 15a. Column chromatography (cyclohex-
ane:petroleum ether ¼ 1:1) was performed for analytical identification. t-4-(2-Acetoxyethyl)-1,3,3-tri-
methylcyclopentane-R-1,c-2-diol (14a): GLC (180ꢁC): 83%; IR: ꢄꢀ¼ 3440 (br, –OH), 1740 (C¼O),
1240, 1060, 1040 (C–O–C¼) cmꢂ1; MS: m=z ¼ 157 (18, Mþ-CH2COOCH3), 137 (1), 111 (3), 109
(3), 97 (100), 82 (15), 69 (25); 1H NMR (300MHz, CDCl3): ꢅ ¼ 0.84 (s, 3-CH3), 0.95 (s, 3-CH3), 1.29
(s, 1-CH3), 1.30–2.10 (m, 4-CH, 5-CH2, 10-CH2), 2.02 (s, CH3–C(O)–), 2.50–2.90 (bs, 1-OH, 2-OH),

1602
K. Anhalt et al.
3.26 (s, 2-CH), 4.02 (m, 20-CH2) ppm; 13C NMR (50.3MHz, CDCl3): ꢅ ¼ 21.50 (CH3–C(O)–),
24.27=24.50=27.94 (1-CH3, 3-CH3), 29.50 (10-CH2), 43.11 (4-CH), 43.58 (5-CH2), 45.16 (3-C),
64.51 (20-CH2), 77.35 (1-C), 86.67 (2-CH), 171.74 (C¼O) ppm; 3-(2-Acetoxyethyl)-2,2-dimethyl-5-
oxohexanal (15a): GLC (180ꢁC): 78%; MS: m=z ¼ 212 (<1), 175 (7, Mþ-C(CH3)2-CHO), 137 (3),
110 (4), 97 (100), 82 (10), 69 (10); 1H NMR (200MHz, CDCl3): ꢅ ¼ 0.93 (s, 2-CH3), 0.99 (s, 2-CH3),
1.10–2.50 (m, 10-CH2, 3-CH, 4-CH2), 1.99 (s, CH3–C(O)–), 2.11 (s, 6-CH3), 3.95 (t, J ¼ 7.2 Hz, 20-
CH2), 9.37 (s, 1-CHO) ppm; 13C NMR (50.3 MHz, CDCl3): ꢅ ¼ 19.06=19.48 (2-CH3), 21.40 (CH3–
C(O)–), 30.44 (10-CH2), 34.13 (6-CH3), 40.63 (3-CH), 45.12 (4-CH2), 49.51 (2-C), 63.31 (20-CH2),
171.41 (C¼O), 206.03 (1-CHO), 207.39 (5-C¼O) ppm.
b) Reaction of the mixture from a) with Pb(OAc)4 and p-toluenesulfonic acid: According to procedures
II and III 8.0 g of the mixture of 13.2mmol of 14a and 10.5 mmol of 15a yielded without cleaning of
the intermediate product after ball tube distillation 2.0 g (41%) of the colourless liquid 16a. Bp1 165ꢁC;
GLC (180ꢁC): 83%; IR: ꢄꢀ¼ 3040, 740 (–C¼CH), 1740, 1680 (C¼O), 1240, 1050 (C–O–C) cmꢂ1
;
MS: m=z ¼ 210 (5, Mþ), 168 (10, Mþ-C2H2O), 150 (90, Mþ-CH3COOH), 135 (60), 123 (65), 107
(40), 95 (100), 81 (50); 1H NMR (200 MHz, CDCl3): ꢅ ¼ 0.97 (s, 4-CH3), 1.11 (s, 4-CH3), 1.20–2.60
(m, 5-CH, 6-CH2, 10-CH2), 1.99 (s, CH3C(O)–), 4.06 (m, 20-CH2), 5.80 (d, J ¼ 10.0Hz, 2-CH), 6.60 (d,
J ¼ 10.0Hz, 3-CH) ppm; 13C NMR (50.3 MHz, CDCl3): ꢅ ¼ 20.64=27.98 (4-CH3), 21.37 (CH3–C(O)),
29.53 (10-CH2), 36.32 (4-C), 39.63 (6-CH2), 40.77 (5-CH), 62.85 (20-CH2), 126.89 (2-CH), 161.13
(3-CH), 171.34 (C¼O), 199.63 (1-C¼O) ppm.
5-(2-Methoxyethyl)-4,4-dimethylcyclohex-2-enone (16b, C11H18O2)
a) Reaction of fencholene methylether (13b) with KMnO4: According to procedure I 2.61g of fench-
olene methylether [14] (13b) (15.5mmol) and 3.35g of KMnO4 yielded 2.66 g (28% relating to 14b
and 34% to 15b) of a liquid which contained 33% 14b and 39% 15b. Compounds were separated by
column chromatography (petroleum ether:ethyl acetate ¼ 1:1). t-4-(2-Methoxyethyl)-1,3,3-trimethylcy-
clopentane-R-1,c-2-diol (14b): GLC (180ꢁC): 87%; IR: ꢄꢀ¼ 3426 (–OH), 2831 (CH3–O), 1113, 1070
(C–O–C) cmꢂ1; MS: m=z ¼ 202 (<1, Mþ), 184 (2, Mþ-H2O), 169 (1, Mþ-CH3), 152 (2), 129 (100),
97 (90), 43 (94); 1H NMR (200 MHz, CDCl3): ꢅ ¼ 0.83 (s, 3-CH3), 0.94 (s, 3-CH3), 1.20–2.00 (m, 4-
CH, 5-CH2, 10-CH2), 1.28 (s, 1-CH3), 2.63 (bs, 1-OH), 2.83 (d, J ¼ 7.3 Hz, 2-OH), 3.29 (m, 20-CH2),
3.30 (s, CH3–O), 3.33 (s, 2-CH) ppm; 13C NMR (50.3 MHz, CDCl3): ꢅ ¼ 24.25=24.49 (3-CH3), 28.02
(1-CH3), 30.35 (10-CH2), 43.14 (4-CH), 43.76 (3-C, 5-CH2), 58.97 (CH3–O), 72.73 (20-CH2), 76.36
(1-C), 86.74 (2-CH) ppm.
b) Reaction of the crude product of a) with Pb(OAc)4: According to procedure II 2.00g of the mixture
of 6.5 mmol of 14b and 3.9 mmol of 15b yielded after ball tube distillation 0.98g (47%) of the
colourless liquid 3-(2-methoxyethyl)-2,2-dimethyl-5-oxohexanal (15b). Bp0.98 100ꢁC; GLC (180ꢁC):
81%; IR: ꢄꢀ¼ 2831 (CH3–O), 1720 (C¼O), 1117 (C–O–C) cmꢂ1; MS: m=z ¼ 201 (<1, Mþ þ H), 200
(<1, Mþ), 199 (<1, Mþ ꢂ H), 186 (1, Mþ-CH3), 167 (7, Mþ-CH3, –H2O), 111 (10), 97 (18), 82 (35),
1
43 (100); H NMR (200 MHz, CDCl3): ꢅ ¼ 0.92 (s, 2-CH3), 0.97 (s, 2-CH3), 1.34 (m, 1H, 10-CH2),
1.60 (m, 1H, 10-CH2), 2.09 (s, 6-CH3), 2.36 (m, 4-CH2), 2.45 (m, 3-CH), 3.18 (s, CH3–O), 3.28 (m, 20-
CH2), 9.38 (s, 1-CHO) ppm; 13C NMR (50.3 MHz, CDCl3): ꢅ ¼ 19.16=19.29 (2-CH3), 30.48 (6-CH3),
31.48 (10-CH3), 35.27 (3-CH), 45.49 (4-CH2), 49.55 (2-C), 58.73 (CH3–O), 71.89 (20-CH2), 206.35
(1-CHO), 207.56 (5-C¼O) ppm.
c) Reaction of 15b with p-toluenesulfonic acid: According to procedure III 729 mg of 15b (3.64 mmol)
yielded after ball tube distillation 402 mg (61%) of the colourless liquid 16b. Bp1.3 120ꢁC; GLC
(180ꢁC): 88%; IR: ꢄꢀ¼ 3022, 780 (–C¼CH), 2830 (CH3–O), 1680 (C¼O), 1117 (C–O–C) cmꢂ1
;
MS: m=z ¼ 182 (5, Mþ), 167 (7, Mþ-CH3), 150 (23, Mþ-CH4O), 135 (42), 123 (90), 108 (30), 96 (92),
81 (72), 45 (100); 1H NMR (200 MHz, CDCl3): ꢅ ¼ 0.97 (s, 4-CH3), 1.12 (s, 4-CH3), 1.32 (m, 1H, 10-
CH2), 1.84 (m, 1H, 10-CH2), 1.99 (m, 5-CH), 2.12 (m, 1H, 6-CH2), 2.47 (dd, J ¼ 16.3, 3.7 Hz, 1H,

Synthesis of Chiral Cyclohexenones
1603
6-CH2), 3.27 (s, CH3–O), 3.33 (m, 20-CH2), 5.80 (d, J ¼ 10.2Hz, 2-CH), 6.60 (d, J ¼ 10.2Hz, 3-CH)
ppm; 13C NMR (50.3MHz, CDCl3): ꢅ ¼ 20.71=28.00 (4-CH3), 30.42 (10-CH2), 36.35 (4-C), 39.67 (6-
CH2), 40.65 (5-CH), 59.10 (CH3–O), 70.93 (20-CH2), 126.84 (2-CH), 161.48 (3-CH), 200.26 (1-C¼O)
ppm.
d) Ozonolyses of fencholene methylether (13b), decomposition of the ozonide, and cyclisation with p-
toluenesulfonic acid: According to procedures IV, V, and III 1.62g of fencholene methylether (13b)
(9.64 mmol) yielded without purification of the intermediate products after final ball tube distillation
0.76g (44%) of cyclohexenone 16b.
Reaction of 2-[(4-Acetoxy-2,3,3-trimethylcyclopent-1-enyl)methyl]-
1,3-dioxolane (8a) with KMnO4
According to procedure I 10.00 g of 8a [5b] (39 mmol) yielded 14.9g of crude product, which
contained 32% 8a, 34% 17, and 15% 18. Compounds were separated by column chromatography
(petroleum ether:ethyl acetate ¼ 1:3). 1-(1,3-Dioxolan-2-yl)-5,5-dimethylhept-3-en-2,6-dione (17):
GLC (180ꢁC): 94%, IR: ꢄꢀ¼ 1711, 1670 (C¼O), 1621 (>C¼C<), 1127 (C–O–C) cmꢂ1; MS:
m=z ¼ 225 (<1, Mþ-H), 211 (<1, Mþ-CH3), 184 (20, Mþ-C2H2O), 141 (3), 111 (10), 96 (45), 73
1
(100); H NMR (200 MHz, CDCl3): ꢅ ¼ 1.26 (s, 6H, 5-CH3), 2.10 (s, 7-CH3), 2.91 (d, J ¼ 5.0 Hz,
1-CH2), 3.85–3.92 (m, 40-CH2, 50-CH2), 5.23 (t, J ¼ 5.0 Hz, 20-CH), 6.15 (d, J ¼ 16.3 Hz, 3-CH), 6.90
(d, J ¼ 16.3Hz, 4-CH) ppm; 13C NMR (50.3 MHz, CDCl3): ꢅ ¼ 23.96 (5-CH3), 26.38 (7-CH3), 45.49
(1-CH2), 51.26 (5-C), 65.41 (40-CH2, 50-CH2), 101.52 (20-CH), 129.47 (3-CH), 150.99 (4-CH), 196.69
(2-C¼O), 209.36 (6-C¼O) ppm; 2,3,3-Trimethyl-6-oxocyclohexa-1,4-dienecarboxylic acid (2-hydro-
xyethyl)ester (18): GLC (120ꢁC): 96%; IR: ꢄꢀ¼ 3452 (–OH), 1733, 1659 (C¼O), 1625 (>C¼C<),
1247, 1058 (C–O–C¼) cmꢂ1; MS: m=z ¼ 226 (<1, Mþ), 223 (<1), 211 (<1, Mþ-CH3), 194 (50,
Mþ-CH4O), 179 (20), 163 (100), 149 (80); 1H NMR (200MHz, CDCl3): ꢅ ¼ 1.28 (s, 6H, 3-CH3), 2.04
(s, 2-CH3), 3.82 (t, J ¼ 4.6 Hz, 20-CH2), 4.41 (t, J ¼ 4.6 Hz, 10-CH2), 6.21 (d, J ¼ 10.0Hz, 4-CH), 6.84
(d, J ¼ 10.0Hz, 5-CH ppm); 13C NMR (50.3 MHz, CDCl3): ꢅ ¼ 17.16 (2-CH3), 25.99 (3-CH3), 40.80
(3-C), 60.99 (20-CH2), 67.15 (10-CH2), 126.43 (5-CH), 132.95 (1-C), 158.68 (4-CH), 163.93 (2-C),
167.38 (O–C¼O), 183.53 (6-C¼O) ppm.
3-(1,3-Dioxolan-2-yl)methyl-5-methoxy-6,6-dimethylcyclohex-2-enone (21a, C13H20O4)
a) Reaction of 8b with KMnO4: According to procedure I 1.30g of 8b (5.8mmol) and 1.45g
of KMnO4 yielded 1.74g (37% relating to 19a and 51% to 20a) of a mixture which contained
32% 19a and 44% 20a. The products were separated by column chromatography (petroleum ether:
ethyl acetate ¼ 1:3). 2-[(R-1,c-2-Dihydroxy-t-4-methoxy-2,3,3-trimethylcyclopentyl)methyl]-1,3-dioxo-
lane (19a): GLC (180ꢁC): 80%; IR: ꢄꢀ¼ 3478 (–OH), 2824 (CH3–O), 1096 (C–O–C) cmꢂ1; MS:
m=z ¼ 259 (<1, Mþ-H), 245 (<1, Mþ-CH3), 243 (1), 242 (4, Mþ-H2O), 185 (20), 173 (15), 160 (8),
1
143 (10), 73 (100); H NMR (200 MHz, CDCl3): ꢅ ¼ 0.88 (s, 30-CH3), 1.09 (s, 20-CH3), 1.13 (s,
30-CH3), 1.78 (dd, J ¼ 14.0, 7.6 Hz, 1H, 50-CH2), 1.89 (dd, J ¼ 14.4, 7.2 Hz, 1H, CH2), 2.02 (dd,
J ¼ 14.4, 3.2 Hz, 1H, 50-CH2), 2.25 (dd, J ¼ 14.0, 7.6Hz, 1H, 50-CH2), 3.33 (s, CH3–O), 3.67 (t,
J ¼ 7.6 Hz, 40-CH), 3.86 (m, 5-CH2), 3.96 (m, 4-CH2), 5.18 (dd, J ¼ 7.2, 3.2 Hz, 2-CH) ppm; 13C
NMR (50.3MHz, CDCl3): ꢅ ¼ 19.09 (30-CH3), 19.70 (20-CH3), 23.55 (30-CH3), 41.82 (CH2), 42.44
(50-CH2), 47.39 (30-C), 58.06 (CH3–O), 64.92 (5-CH2), 64.96 (4-CH2), 78.60 (10-C), 81.91 (20-C),
86.53 (40-CH), 102.86 (2-CH) ppm; 1-(1,3-Dioxolan-2-yl)-5,5-dimethyl-4-methoxyheptane-2,6-dione
(20a): GLC (180ꢁC): 84%; IR: ꢄꢀ¼ 2831 (CH3–O), 1708 (C¼O), 1132, 1097 (C–O–C) cmꢂ1; MS:
m=z ¼ 259 (<1, Mþ þ H), 258 (<1, Mþ), 257 (<1, Mþ-H), 226 (1, Mþ-CH4O), 184 (1), 173 (18),
139 (4), 129 (6), 85 (12), 73 (100); 1H NMR (200MHz, CDCl3): ꢅ ¼ 1.05 (s, 5-CH3), 1.09 (s, 5-CH3),
2.14 (s, 7-CH3), 2.55 (dd, J ¼ 8.5, 3.7 Hz, 3-CH2), 2.80 (d, J ¼ 5.0 Hz, 1-CH2), 3.29 (s, CH3–O),
3.87–3.96 (m, 4-CH, 40-CH2, 50-CH2), 5.21 (t, J ¼ 5.0 Hz, 20-CH) ppm; 13C NMR (50.3 MHz, CDCl3):

1604
K. Anhalt et al.
ꢅ ¼ 20.78=21.42 (5-CH3), 26.98 (7-CH3), 46.07 (3-CH2), 48.51 (1-CH2), 52.61 (5-C), 59.85 (CH3–O),
65.41 (40-CH2, 50-CH2), 81.12 (4-CH), 101.21 (20-CH), 205.9 (2-C¼O), 213.10 (6-C¼O) ppm.
b) Reaction of the crude product of a) with Pb(OAc)4 and p-toluenesulfonic acid: According to
procedures II and III 1.30 g of the mixture of 19a and 20a (1.6mmol relating to 19a and 2.2mmol
to 20a) yielded as crude product 73% compound 20a which reacted with p-toluenesulfonic acid
according to procedure III to 0.94g (14% relating to 21a) of a mixture which contained 41% 17,
12% 22, and 14% 21a. The compounds were separated by column chromatography (petroleum
ether:ethyl acetate ¼ 1:1). 21a: GLC (180ꢁC): 63%; MS: m=z ¼ 240 (2, Mþ), 226 (<1), 225 (<1,
1
Mþ-CH3), 195 (<1, Mþ-C2H5O), 153 (2), 135 (2), 86 (18), 73 (100); H NMR (200MHz, CDCl3):
ꢅ ¼ 1.05 (s, 6-CH3), 1.12 (s, 6-CH3), 2.00–3.00 (m, CH2), 2.53 (d, J ¼ 6.1 Hz, 4-CH2), 3.36 (s, CH3–
O), 2.83–3.97 (m, 5-CH), 4.99 (t, J ¼ 4.7 Hz, 20-CH), 5.88 (s, 2-CH) ppm; 13C NMR (50.3MHz,
CDCl3): ꢅ ¼ 19.16=22.31 (6-CH3), 32.74 (4-CH2), 42.62 (CH2), 47.12 (6-C), 58.34 (CH3–O), 65.45
(40-CH2, 50-CH2), 83.98 (5-CH), 103.16 (20-CH), 127.41 (2-CH), 154.09 (3-C), 203.55 (1-C¼O) ppm;
2,3,3-Trimethyl-6-oxocyclohexa-1,4-dienecarbaldehyde (22): GLC (120ꢁC): 74%; IR: ꢄꢀ¼ 1734, 1659
(C¼O), 1624 (>C¼C<) cmꢂ1; MS: m=z ¼ 164 (1, Mþ), 151 (10), 149 (100, Mþ-CH3), 136 (18, Mþ-
CO), 121 (43, Mþ-CH3CO), 91 (31); 1H NMR (200 MHz, CDCl3): ꢅ ¼ 1.32 (s, 6H, 3-CH3), 2.35 (s, 2-
CH3), 6.23 (d, J ¼ 9.9 Hz, 5-CH), 6.80 (d, J ¼ 9.9Hz, 4-CH), 10.40 (s, CHO) ppm; 13C NMR
(50.3MHz, CDCl3): ꢅ ¼ 17.35 (2-CH3), 26.25 (3-CH3), 41.91 (3-C), 127.08 (5-CH), 130.35 (1-C),
157.61 (4-CH), 173.82 (2-C), 186.02 (6-C¼O), 194.74 (CHO) ppm.
5-Ethoxy-3-(2-methoxyethyl)-6,6-dimethylcyclohex-2-enone (21b, C13H22O2)
a) Reaction of 8c with KMnO4: According to procedure I 2.85 g of 8c (13.4 mmol) and 4.20g
of KMnO4 yielded 2.67 g of a crude product which contained 11% 19b, 66% 20b, and 10%
23. Compounds were separated partially by column chromatography (petroleum ether:ethyl
acetate ¼ 1.5:1). t-4-Ethoxy-1-(2-methoxyethyl)-2,3,3-trimethylcyclopentane-R-1,c-2-diol (19b): GLC
(180ꢁC): 37% 19b beside 56% 20b; MS: m=z ¼ 231 (<1, Mþ-CH3), 228 (6, Mþ-H2O), 213 (5,
1
Mþ-CH3, –H2O), 167 (15), 157 (65), 132 (12), 115 (10), 99 (100); H NMR (200 MHz, CDCl3)
(simultaneously with 20b): ꢅ ¼ 0.80 (s, 3-CH3), 1.07 (s, 3-CH3), 1.13 (s, 2-CH3), 1.78 (bs, 1-OH),
2.14 (bs, 2-OH), 3.37 (s, CH3–O) ppm; 13C NMR (50.3 MHz, CDCl3) (simultaneously with 20b):
ꢅ ¼ 15.99 (CH3–CH2–O), 19.46=19.86=27.70 (2-CH3, 3-CH3), 37.83 (10-CH2), 43.27 (5-CH2),
47.95 (3-C), 59.43 (CH3–O), 66.24 (CH3–CH2–O), 70.79 (20-CH2), 80.89 (1-C), 82.02 (2-C),
84.81 (4-CH) ppm; 4-Ethoxy-8-methoxy-3,3-dimethyloctane-2,6-dione (20b): GLC (180ꢁC): 90%;
IR: ꢄꢀ¼ 2830 (CH3–O), 2360, 1708 (C¼O), 1116, 1093 (C–O–C) cmꢂ1; MS: m=z ¼ 244 (1, Mþ),
229 (2, Mþ-CH3), 226 (1, Mþ-H2O), 212 (5, Mþ-CH4O), 198 (7, Mþ-C2H6O), 159 (68), 143 (5),
1
129 (5), 100 (10), 87 (100); H NMR (200MHz, CDCl3): ꢅ ¼ 1.05 (s, 3-CH3), 1.08 (s, 3-CH3),
1.05 (t, J ¼ 6.8 Hz, CH3–CH2–O), 2.14 (s, 1-CH3), 2.50 (2d, J ¼ 7.3, 3.6 Hz, 5-CH2), 2.66 (t,
J ¼ 6.2 Hz, 7-CH2), 3.30 (s, CH3–O), 3.40 (m, CH3–CH2–O), 3.60 (t, J ¼ 6.2 Hz, 8-CH2), 4.04 (dd,
J ¼ 7.3, 3.6Hz, 4-CH) ppm; 13C NMR (50.3 MHz, CDCl3): ꢅ ¼ 15.94 (CH3–CH2–O), 20.98=21.98
(3-CH3), 27.18 (1-CH3), 44.18 (7-CH2), 45.77 (5-CH2), 52.60 (3-C), 59.25 (CH3–O), 67.57 (CH3–
CH2–O), 67.86 (8-CH2), 79.90 (4-CH), 208.08 (6-C¼O), 213.41 (2-C¼O) ppm; 5-Ethoxy-3-
hydroxy-2-methoxymethyl-3,4,4-trimethylcyclohexanone (23): GLC (180ꢁC): 74%; IR: ꢄꢀ¼ 3480
(–OH), 2817 (CH3–O), 1711 (C¼O), 1102 (C–O–C) cmꢂ1; MS: m=z ¼ 229 (<1, Mþ-CH3),
226 (<1, Mþ-H2O), 211 (<1, Mþ-CH3, –H2O), 198 (2), 175 (1), 166 (1), 151 (8), 143 (10),
1
127 (15), 100 (100); H NMR (200 MHz, CDCl3): ꢅ ¼ 1.03 (s, 4-CH3), 1.21 (s, 4-CH3), 1.11 (s, 3-
CH3), 1.16 (t, J ¼ 7.0 Hz, CH3–CH2–O), 2.51–2.67 (m, 6-CH2), 3.16 (m, 2-CH), 3.19 (m, 5-CH),
3.37 (s, CH3–O), 3.56 (m, CH3–CH2–O), 3.77–3.85 (m, 2-CH–CH2–O) ppm; 13C NMR
(50.3MHz, CDCl3): ꢅ ¼ 15.94 (CH3–CH2–O), 16.31=20.16 (4-CH3), 21.11 (3-CH3), 44.70 (4-C),
45.09 (6-CH2), 55.27 (2-CH), 59.82 (CH3–O), 66.31 (CH3–CH2–O), 70.50 (2-CH–CH2–O), 77.14
(3-C) 80.50 (5-CH), 206.77 (1-C¼O) ppm.

Synthesis of Chiral Cyclohexenones
1605
b) Reaction of 20b with p-toluenesulfonic acid: According to procedure III 234 mg of 20b (0.96 mmol)
yielded a mixture (270 mg) which contained 25% 4a, 40% 24b, 13% 24c, and 11% 21b. Compounds
were separated partially by column chromatography (petroleum ether:ethyl acetate¼ 1:1). 8-Methoxy-
3,3-dimethyloct-4-ene-2,6-dione (24a): GLC (180ꢁC): 92%; IR: ꢄꢀ¼ 2829, 2815 (CH3–O), 1711,
1674 (C¼O), 1624 (>C¼C<), 1119 (C–O–C) cmꢂ1; MS: m=z ¼ 199 (<1, Mþ þ H), 183
(<1, Mþ-CH3), 167 (<1, Mþ-CH3–O), 156 (85, Mþ-C2H2O), 139 (1), 128 (18), 111 (20), 96
1
(65), 87 (43), 43 (100); H NMR (200MHz, CDCl3): ꢅ ¼ 1.28 (s, 6H, 3-CH3), 2.12 (s, 1-CH3), 2.81
(t, J ¼ 6.3 Hz, 7-CH2), 3.31 (s, CH3–O), 3.67 (t, J ¼ 6.3Hz, 8-CH2), 6.15 (d, J ¼ 16.2Hz, 5-CH),
6.91 (d, J ¼ 16.2Hz, 4-CH) ppm; 13C NMR (50.3 MHz, CDCl3): ꢅ ¼ 24.00 (3-CH3), 26.37 (1-CH3),
41.04 (7-CH2), 51.22 (3-C), 59.31 (CH3–O), 68.08 (8-CH2), 129.31 (5-CH), 150.34 (4-CH), 198.60
(6-C¼O), 209.46 (2-C¼O) ppm; 3,3-Dimethylocta-4,7-diene-2,6-dione (24b): GLC (180ꢁC): 91%;
IR: ꢄꢀ¼ 1712, 1667 (C¼O), 1625, 1612 (>C¼C<) cmꢂ1; MS: m=z ¼ 167 (<1, Mþ þ H), 151
1
(<1, Mþ-CH3), 124 (45, Mþ-C2H2O), 109 (100), 107 (5), 95 (8), 81 (12); H NMR (200 MHz,
CDCl3): ꢅ ¼ 1.31 (s, 6H, 3-CH3), 2.14 (s, 1-CH3), 5.86 (dd, J ¼ 10.5, 1.3 Hz, 1H, 8-CH2), 6.29 (dd,
J ¼ 17.5, 1.3 Hz, 1H, 8-CH2), 6.40 (d, J ¼ 16.1Hz, 5-CH), 6.60 (dd, J ¼ 17.5, 10.5 Hz, 7-CH), 7.00
(d, J ¼ 16.1Hz, 4-CH) ppm; 13C NMR (50.3 MHz, CDCl3): ꢅ ¼ 23.97 (3-CH3), 26.40 (1-CH3),
51.37 (3-C), 126.97 (5-CH), 129.67 (8-CH2), 135.50 (7-CH), 151.22 (4-CH), 189.93 (6-C¼O),
209.31 (2-C¼O) ppm; 8-Hydroxy-3,3-dimethyloct-4-ene-2,6-dione (24c): GLC (180ꢁC): 62% 24b
and 29% 21b; MS: m=z ¼ 170 (85), 139 (1, Mþ-C2H5O), 124 (20), 101 (32), 97 (72), 81 (25), 43
1
(100); H NMR (200MHz, CDCl3) (simultaneously with 21b): ꢅ ¼ 1.28 (s, 6H, 3-CH3), 2.12 (s, 1-
CH3), 2.82 (t, J ¼ 6.4 Hz, 7-CH2), 3.70 (t, J ¼ 6.4 Hz, 8-CH2) 6.15 (d, J ¼ 16.3Hz, 5-CH), 6.91
(d, J ¼ 16.3Hz, 4-CH) ppm; 13C NMR (50.3 MHz, CDCl3) (simultaneously with 21b): ꢅ ¼ 23.90
(3-CH3), 26.31 (1-CH3), 41.13 (7-CH2), 51.17 (3-C), 65.94 (8-CH2), 129.46 (5-CH), 150.34 (4-CH),
199.00 (6-C¼O), 209.66 (2-C¼O) ppm; 21b: MS: m=z ¼ 226 (<1, Mþ), 211 (<1, Mþ-CH3), 194
1
(39, Mþ-CH4O), 180 (25), 167 (15), 149 (15), 135 (17), 121 (18), 107 (24), 100 (100); H NMR
(200 MHz, CDCl3) (simultaneously with 24c): ꢅ ¼ 1.04 (s, 6-CH3), 1.12 (s, 6-CH3), 1.15
(t, J ¼ 6.9 Hz, CH3–CH2–O), 2.44 (t, J ¼ 6.4 Hz, 10-CH2), 2.53–2.62 (m, 4-CH2), 3.32 (s,
CH3–O), 3.47 (m, CH3–CH2–O), 3.53 (t, J ¼ 6.4 Hz, 20-CH2), 5.82 (bs, 2-CH) ppm; 13C NMR
(50.3MHz, CDCl3) (simultaneously with 24c): ꢅ ¼ 15.47 (CH3–CH2–O), 19.04=22.10 (6-CH3),
33.13=38.02 (4-CH2, 10-CH2), 47.13 (6-C), 59.15 (CH3–O), 67.97 (CH3–CH2–O), 70.41 (20-CH2),
81.89 (5-CH), 125.77 (2-CH), 157.49 (3-C), 204.17 (1-C¼O) ppm.
c) Ozonolyses of 8c and decomposition of the ozonide to 20b: According to procedures IVand V 1.90 g
of 8c (8.96 mmol) yielded without purification of the intermediate products after final ball tube
distillation 1.11 g (51%) of the liquid 20b.
d) Reaction of 20b with NaOH=EtOH: To a stirred soln. of 234 mg of 20b (0.96 mmol) in 10cm3 of
ethanol at rt 100 mg of KOH in 3 cm3 of ethanol were added and refluxed about 15min. After that
100 cm3 of diethyl ether were added and the organic layer was washed with H2O, sat. NH4Cl-soln.,
brine, dried (Na2SO4), and concentrated. Purification by column chromatography (petroleum ether:
ethyl acetate ¼ 2:1) yielded 64mg (39%) of 25a and 25mg (16%) of 25b. 2-Methoxymethyl-3,4,4-
trimethylcyclohexa-2,5-dienone (25a): GLC (180ꢁC): 96%; IR: ꢄꢀ¼ 2813 (CH3–O), 1662, 1628
(C¼O), 1624 (>C¼C<), 1105, 1086 (C–O–C) cmꢂ1; MS: m=z ¼ 180 (<1, Mþ), 179 (<1,
1
Mþ-H), 165 (100, Mþ-CH3), 150 (30), 135 (20), 122 (12), 105 (10); H NMR (200MHz, CDCl3):
ꢅ ¼ 1.25 (s, 6H, 4-CH3), 2.08 (s, 3-CH3), 3.34 (s, CH3–O), 4.29 (s, CH2–O), 6.20 (d, J ¼ 9.9 Hz,
6-CH), 6.74 (d, J ¼ 9.9 Hz, 5-CH) ppm; 13C NMR (50.3 MHz, CDCl3): ꢅ ¼ 16.10 (3-CH3), 26.47
(4-CH3), 40.84 (4-C), 58.74 (CH3–O), 64.84 (CH2–O), 126.73 (6-CH), 132.20 (2-C), 157.14
(5-CH), 164.88 (3-C), 185.24 (1-C¼O) ppm; 2-Ethoxymethyl-3,4,4-trimethylcyclohexa-2,5-dienone
(25b): GLC (120ꢁC): 82%; IR: ꢄꢀ¼ 2809 (CH3–O), 1664, 1629 (C¼O), 1097 (C–O–C) cmꢂ1; MS:
m=z ¼ 195 (<1, Mþ þ H), 194 (<1, Mþ), 179 (100, Mþ-CH3), 151 (80, Mþ-CH3, –CO), 135 (20),
123 (25), 105 (18), 91 (20); 1H NMR (200MHz, CDCl3): ꢅ ¼ 1.18 (t, J ¼ 7.2 Hz, CH3–CH2–O), 1.24
(s, 6H, 4-CH3), 2.08 (s, 3-CH3), 3.50 (t, J ¼ 7.2 Hz, CH3–CH2–O), 4.32 (s, 2-C–CH2–O), 6.18

1606
K. Anhalt et al.: Synthesis of Chiral Cyclohexenones
(d, J ¼ 9.9 Hz, 6-CH), 6.68 (d, J ¼ 9.9 Hz, 5-CH) ppm; 13C NMR (50.3 MHz, CDCl3): ꢅ ¼ 15.63
(CH3–CH2–O), 16.03 (3-CH3), 26.36 (4-CH3), 40.77 (4-C), 62.78 (CH3–CH2–O), 66.27
(2-C–CH2–O), 126.81 (6-CH), 132.40 (2-C), 157.15 (5-CH), 164.89 (3-C), 185.40 (1-C¼O) ppm.
Acknowledgements
We would like to thank the Deutsche Forschungsgemeinschaft, the Fonds der Chemischen Industrie,
and DRAGOCO Gerberding & Co. GmbH for financial support.
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