A novel aldol condensation alternative: α,β-unsaturated aldehydes from 3-hydroxy-1-alkynes via dihydrodioxepins

Article abstract of DOI:10.1002/(SICI)1521-3765(19980904)4:9<1738::AID-CHEM1738>3.0.CO;2-P

The controlled aldol condensation between an aliphatic ketone and an acetaldehyde equivalent remains a challenge. One solution to this evergreen problem consists of the nucleophilic addition of acetylene to the ketone and the subsequent isomerization of the resulting 3-hydroxy-1-alkyne to the corresponding 2-alkenal. So far, however, the latter Step could only be executed with acid-insensitive substrates. We now present a milder, three-step method which extends the scope of the procedure considerably. In the first step, the 3-hydroxy-1-alkynes are converted into 2-propynyl ethylene glycol monoethers; these then undergo base-catalyzed cyclization to give the dihydro-1,4-dioxepins, which are hydrolyzed in acidic medium in the third and final step.

Full text of DOI:10.1002/(SICI)1521-3765(19980904)4:9<1738::AID-CHEM1738>3.0.CO;2-P

FULL PAPER
A Novel Aldol Condensation Alternative: a,b-Unsaturated Aldehydes from
3-Hydroxy-1-alkynes via Dihydrodioxepins
Heng-xu Wei and Manfred Schlosser*
Abstract: The controlled aldol condensation between an aliphatic ketone and an
acetaldehyde equivalent remains a challenge. One solution to this evergreen problem
consists of the nucleophilic addition of acetylene to the ketone and the subsequent
isomerization of the resulting 3-hydroxy-1-alkyne to the corresponding 2-alkenal. So
Keywords: aldehydes ´ aldol con-
far, however, the latter step could only be executed with acid-insensitive substrates.
densation ´ alkynes ´ enethers ´
We now present a milder, three-step method which extends the scope of the
retinoids
procedure considerably. In the first step, the 3-hydroxy-1-alkynes are converted into
2-propynyl ethylene glycol monoethers; these then undergo base-catalyzed cycliza-
tion to give the dihydro-1,4-dioxepins, which are hydrolyzed in acidic medium in the
third and final step.
Introduction
Terminal alkynes can be hydrated under acid and mercuric
salt catalysis to afford 2-alkanones.[1] In contrast, a simple
method is lacking that would allow the generation of
aldehydes from 1-alkynes. Such a transformation, however,
can be accomplished with 3-hydroxy-1-alkynes as the sub-
strates, as has been demonstrated by Pauling et al.[2] In the
presence of a silylated vanadium catalyst, the alkynol isomer-
izes, presumably through an allenol intermediate, to the a,b-
unsaturated aldehyde. For example, 3,7-dimethyl-6-octen-1-
yn-3-ol gives citral (as a 1:3 mixture of neral and geranial) in
almost quantitative yield. Unfortunately, the scope of this
process is restricted to acid-insensitive substrates. Ethynyl-b-
ionol does not afford b-ionylideneacetaldehyde, a versatile
C15-building block; rather, it decomposes after dehydration to
give the corresponding trienyne (Scheme 1).
The most straightforward route to b-ionylideneacetalde-
hyde (again obtained as a mixture of geometrical isomers[3]) is
based on the addition of (Z)-2-ethoxyvinyllithium[4] to b-
ionone and the subsequent hydrolysis of the resulting (Z)-2-
ethoxyvinyl-b-ionol under acidic conditions. However, from
an economic point of view, it would be attractive to avoid the
expensive organometallic reagent and to apply a two-step
Scheme 1. The reaction of an acid-insensitive substrate affords the a,b-
unsaturated aldehyde, whereas an acid-sensitive substrate, ethynyl-b-ionol,
does not.
sequence starting with the ethynylation of b-ionone, followed
by the addition of ethanol onto the triple bond of the resulting
ethynyl-b-ionol (Scheme 2). However, this goal can be
achieved only indirectly.
[*] Prof. Dr. M. Schlosser, H.-x. Wei
Â
Institut de Chimie organique de lꢀUniversite
Ã
Batiment de Chimie (BCh)
CH-1015 Lausanne (Switzerland)
Fax: ( ‡ 41)21-692-3965
Scheme 2. Possibilities for the synthesis of b-ionylideneacetaldehyde.
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Chem. Eur. J. 1998, 4, No. 9

1738±1743
carbon atom of the enether unit were preferentially proto-
nated, the hydrolysis of dioxepins 2 and methylenedioxanes 4
would provide 3-(2-hydroxyethoxy)-substituted aldehydes
and 2-alkanones, respectively. At least in the latter case, a
subsequent elimination of ethylene glycol to produce enones
would be extremely difficult to accomplish.
The few literature precedents found were anything but
encouraging. Ethylene glycol monoethers derived from 2-
propyn-1-ol (propargyl alcohol), 2-butyn-1-ol, and 3-butyn-2-
ol gave upon cyclization mainly five- and six-membered and
only minor amounts of seven-membered rings (yields averag-
ing 5% except in two cases when 15% and 29% were
reached).[6] The first example we studied appeared to confirm
this trend. When dissolved in a mixture of potassium tert-
butoxide and tert-butyl alcohol and heated under reflux, 2-
[(1,1-dimethyl-3-phenyl-2-propynyl)oxy]ethanol (6) rapidly
reacted to give a mixture of (Z)- and (E)-3-benzylidene-2,2-
dimethyl-1,4-dioxane (7; 81%) along with a small quantity of
3,5-dihydro-5,5-dimethyl-7-phenyl-2H-1,4-dioxepin (8; 5%)
(Scheme 5). To our delight, the regioselectivity of the intra-
Results and Discussion
Despite numerous attempts, we did not succeed in achieving a
direct conversion of ethynyl-b-ionol into the enether under
acceptable conditions. The base-catalyzed addition of meth-
anol or ethanol to triple bonds is known, but it is restricted to
acetylene itself and derivatives thereof endowed with activat-
ing, that is carbanion-stabilizing, substituents (such as ethy-
nylbenzene or propiolic acid esters).[5]
If an intermolecular reaction fails, the entropy-conserving
intramolecular version may offer a better chance. By combin-
ing various 1-alkyn-3-ols with oxirane or, more conveniently,
ethylene sulfite we prepared a series of ethylene glycol
monoethers 1. The question was now whether the base-
catalyzed cyclization, if it occurred at all, would choose the
desired course leading to dihydro-1,4-dioxepins 2 or take the
wrong track and give methylene-1,4-dioxanes 4. Depending
on the intermediate, acid-promoted hydrolysis would afford
enals 3 or hydroxyketones 5 (Scheme 3).
Scheme 5. Reaction of 2-[(1,1-dimethyl-3-phenyl-2-propynyl)oxy]ethanol
(6) to give dioxane 7 and a small quantity of dioxepin 8.
Scheme 3. Possible intramolecular base-catalyzed cyclization reactions of
ethylene glycol monoethers 1.
molecular addition of the alcohol to a triple bond changed
profoundly when we used starting materials 1 which carry no
substituent at the terminal acetylenic position. The dioxepins
2 now became the predominant products (Table 1).
The predicted outcome is based on the assumption that in
either case the hydrolysis involves as the key intermediate a
(2-hydroxyethyloxy)allyl cation, which is formed by the
heterolytic scission of the bond between the tertiary carbon
atom and the protonated oxygen atom attached to it (as
exemplified for the dioxepins 2 in Scheme 4). If instead the b-
Table 1. Base-catalyzed cyclization of 2-[(1-R-1-methyl-2-propynyl)oxy]e-
thanols 1: total yields of products and ratios of six- versus seven-membered
rings (4 vs. 2) formed.
Scheme 4. Possible rearrangements of the key intermediate, the (2-
hydroxyethyloxy)allyl cation, produced during hydrolysis.
Abstract in German: 3-Hydroxy-1-alkine lassen sich auf
einfache Weise in 2-Alkenale umwandeln. Das dreistufige
Verfahren besteht aus der Herstellung von 2-Propinylethyl-
englykolmonoethern 1, deren basekatalysierter Cyclisierung zu
Dihydro-1,4-dioxepinen 2 und deren säurekatalysierter Hydro-
lyse. Die Methode kann auf wertvolle Zwischenstufen der
Isoprenoid-Synthese, etwa auf Ethinyl-b-ionol, erfolgreich
angewendet werden.
The acid-catalyzed hydrolysis was accomplished with a 1m
solution of hydrogen chloride in 20% aqueous tetrahydrofur-
an (5 h under reflux) and proceeded as expected. The dioxane
7 gave the 3-hydroxy-2-alkanone 9, while enals 3a ± f were
obtained from the dioxepins 2a ± f (Table 2). In general, the
Chem. Eur. J. 1998, 4, No. 9
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1739

M. Schlosser and H.-x. Wei
FULL PAPER
Table 2. Products formed upon acidic hydrolysis of dioxane
dioxepins 2a ± f: yields and, where applicable, Z/E ratios.
7
and
at 08C and the mixture was then stirred for 1 h at 08C. Diethyl ether
(0.10 L) and water (0.10 L) were added and the aqueous layer extracted
with diethyl ether (3 Â 0.10 L). The combined organic phases were washed
with water (3 Â 50 mL) and brine (0.10 L), then dried. After evaporation of
the solvent, the residue was distilled to give a colorless liquid. Yield: 11.0 g
(55%); b.p. 90 ± 928C/0.07 mmHg; d240 ˆ 1.05; nD20 ˆ 1.5245; 1H NMR: d ˆ
7.6 (m, 2H), 7.4 (m, 2H), 7.3 (m, 1H), 3.7 (m, 3H), 3.3 (m, 1H), 2.75 (s, 1H),
‡
2.08 (brs, 1H), 1.77 (s, 3H); MS: 175 (48%, [M
15]), 146 (9%), 129
(100%), 105 (48%); anal. calcd for C12H14O2 (190.24): C 75.76, H 7.42;
found C 75.67, H 7.19%.
2-[(1,5-Dimethyl-1-ethynyl-4-hexenyl)oxy]ethanol (1c): Prepared as de-
scribed for 1b from 3,7-dimethyloct-6-en-1-yn-3-ol (4.3 mL, 3.8 g,
25 mmol). Yield: 1.8 g (37%); b.p. 83 ± 858C/0.2 mmHg (ref. [12]: b.p.
85 ± 928C/0.4 mmHg); d420 ˆ 0.96; nD20 ˆ 1.4706 (ref. [12]: n2D0 ˆ 1.4712); 1H
NMR: d ˆ 5.1 (m, 1H), 3.7 (m, 4H), 2.47 (s, 1H), 2.1 (m, 2H), 2.03 (s, 1H),
1.7 (m, 2H), 1.68 (d, J ˆ 0.9 Hz, 3H), 1.62 (s, 3H), 1.44 (s, 3H); MS: 197
‡
(11%, [M ‡1]), 119 (100%); anal. calcd for C12H20O2 (196.29): C 73.43, H
10.27; found C 73.47, H 10.07%.
2-[[1-Ethynyl-1-methyl-3-(2,6,6-trimethylcyclohexenyl)-2-propenyl]oxy]-
ethanol (1d): Due to the instability of the substrate in the presence of bases,
in particular sodium hydride, at 08C, the standard protocol (see preparation
of compound 1b, above) had to be modified: at
758C, butyllithium
(25 mmol) in hexane (17 mL) and ethylene sulfite (1.9 mL, 2.7 g, 25 mmol)
were consecutively added to ethynyl-b-ionol (5.8 mL, 5.5 g, 25 mmol) in a
mixture of diethyl ether (0.10 L) and hexamethylphosphoric triamide
(9.0 mL, 8.2 g, 50 mmol). The solution was kept at 758C for 1 h and then
allowed to warm to 258C. Water (0.10 L) was added and the product was
extracted with diethyl ether (3 Â 0.10 L). After evaporation of the solvent,
the residue was eluted from silica gel with a mixture of ethyl acetate and
hexanes [1:4 (v/v)] to afford a colorless oil. Yield: 3.1 g (47%); d240 ˆ 1.03;
n2D0 ˆ 1.4950; 1H NMR: d ˆ 6.45 (dm, J ˆ 16.0 Hz, 1H), 5.33 (d, J ˆ 16.0 Hz,
1H), 3.7 (m, 3H), 3.5 (m, 1H), 2.63 (s, 1H), 2.0 (m, 1H), 1.98 (t, J ˆ 6.3 Hz,
2H), 1.66 (d, J ˆ 0.9 Hz, 3H), 1.61 (s, 3H), 1.6 (m, 2H), 1.5 (m, 2H), 1.01 (s,
products were isolated as a mixture of Z and E isomers in
ratios ranging from 1:2 to 1:3. 3-Methyl-2-penten-4-ynal (3 f)
was the only exception. In agreement with the thermody-
namic preference of simple 2-alken-4-ynes[7] for the cis
configuration, its Z isomer was found to predominate.
The 3,5-dihydro-5-ethynyl-5-methyl-2H-1,4-dioxepin (2 f)
can be used as an unorthodox[8] isoprenoid C6 unit. After
deprotonation (with butyllithium) to the corresponding
lithium acetylide, it was added to the C14 aldehyde (E)-2-
methyl-4-(2,6,6-trimethyl-1-cyclohexenyl)-2-butenal, the cor-
nerstone of Islerꢀs synthesis of vitamin A.[9] Alcohol 10
(obtained in 91% yield) was then submitted to consecutive
dehydration (to dioxepin 11) and hydrolysis to afford 11,12-
dehydroretinal 12 (62%; (Z)D13/(E)D13 4:1) (Scheme 6).
‡
‡
3H), 0.99 (s, 3H); MS: 263 (8%, [M ‡1]), 262 (23%, [M ]), 247 (100%);
anal. calcd for C17H26O2 (262.39): C 77.82, H 9.99; found C 78.03, H 9.84%.
2-[(1-Ethynyl-1-methyl-2-propenyl)oxy]ethanol (1e): Prepared as descri-
bed for 1b from 3-methylpent-1-en-4-yn-3-ol (2.8 mL, 2.4 g, 25 mmol).
Yield: 2.1 g (60%); b.p. 59 ± 608C/3 mmHg; d240 ˆ 0.97; nD20 ˆ 1.4571; 1H
NMR: d ˆ 5.75 (dd, J ˆ 17.2, 10.2 Hz, 1H), 5.59 (brd, J ˆ 17.2 Hz, 1H), 5.27
(brd, J ˆ 10.2 Hz, 1H), 3.7 (m, 2H), 3.6 (m, 1H), 3.5 (m, 1H), 2.61 (s, 1H),
‡
‡
2.05 (brs, 1H), 1.57 (s, 1H); MS: 141 (1%, [M ‡1]), 140 (3%, [M ]), 125
(100%); anal. calcd for C8H12O2 (140.18): C 68.55, H 8.63; found C 68.50, H
8.54%.
2-[(1-Ethynyl-1-methyl-2-propynyl)oxy]ethanol (1 f): Analogously ob-
tained from 3-methylpent-1,4-diyn-3-ol[13] (2.4 g, 25 mmol). Yield: 2.1 g
1
(60%); b.p. 60 ± 618C/2 mmHg; d240 ˆ 0.98; nD20 ˆ 1.4605; H NMR: d ˆ 3.9
(m, 2H), 3.8 (m, 2H), 2.57 (s, 2H), 2.0 (brs, 1H), 1.81 (s, 3H); MS: 123
‡
(25%, [M
15]), 107 (14%), 77 (100%); anal. calcd for C8H10O2 (138.17):
C 69.55, H 7.29; found C 69.60, H 7.39%.
2-[(1,1-Dimethyl-3-phenyl-2-propenyl)oxy]ethanol (6): A mixture contain-
ing 2-[(1,1-dimethylprop-2-ynyl)oxy]ethanol[11] (3.4 mL, 3.2 g, 25 mmol),
bromobenzene (4.0 mL, 5.9 g, 38 mmol), tetrakis(triphenylphospine)palla-
dium (65 mg, 0.056 mmol), copper bromide (28 mg, 0.20 mmol), lithium
bromide (90 mg, 1.00 mmol), and piperidine (20 mL) was heated to 908C
with stirring. When the exothermic reaction (which raised the temperature
temporarily to about 1108C) had ceased, the mixture was heated to 1008C
for an additional 30 min. Water (0.10 L) was added and the product then
extracted with diethyl ether (4 Â 0.10 L). The combined organic layers were
dried and evaporated. Distillation of the residue gave a colorless liquid.
Scheme 6. Synthesis of 11,12-dehydroretinal (12).
Experimental Section
1
Yield: 4.8 g (86%); b.p. 98 ± 1008C/0.3 mmHg; d240 ˆ 1.04; nD20 ˆ 1.5353; H
General: For standard working practice and abbreviations see recent
publications from this laboratory (e.g. ref. [10]). 1H NMR spectra were
recorded at 400 MHz in deuterochloroform.
NMR: d ˆ 7.4 (m, 2H), 7.3 (m, 2H), 3.8 (m, 4H), 1.61 (s, 1H), 1.56 (s, 6H);
‡
‡
MS: 205 (2%, [M ‡1]), 204 (1%, [M ]), 160 (52%), 143 (100%); anal.
calcd for C13H16O2 (204.27): C 76.44, H 7.89; found C 76.51, H 8.04%.
Preparation of 2-[(2-propynyl)oxy]ethanols 1 and 6:
Dioxepins and dioxanes:
2-[(1,1-Dimethyl-2-propynyl)oxy]ethanol (1a): B.p. 78 ± 808C/20 mmHg
(ref. [11]: b.p. 171 ± 1728C); n2D0 ˆ 1.4524.
2-[(1-Methyl-1-phenyl-2-propynyl)oxy]ethanol (1b): Sodium hydride
(0.72 g, 30 mmol) was added to a solution of 2-phenyl-3-butyn-2-ol (3.7 g,
25 mmol) in dimethylformamide (0.10 L) at 08C. After the evolution of
hydrogen had ceased, ethylene sulfite (2.3 mL, 3.3 g, 30 mmol) was added
(Z)-3-Benzylidene-2,2-dimethyl-1,4-dioxane [(Z)-7]: A solution of 2-[(1,1-
dimethyl-3-phenyl-2-propynyl)oxy]ethanol (6; 4.9 mL, 5.1 g, 25 mmol) in
tert-butyl alcohol (5 mL) was added dropwise to a boiling solution of
potassium tert-butoxide (2.8 g, 25 mmol) in tert-butyl alcohol (20 mL). The
solution was heated under reflux for 12 h. Water (0.10 L) was added and the
product then extracted with diethyl ether (3 Â 0.10 L), dried, and the
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Aldehyde Synthesis
1738±1743
solvent evaporated. Distillation gave a liquid product which, according to
gas chromatography (30 m, DB-1, 1008C; 30 m, DB-WAX, 1008C),
contained the dioxanes (Z)-7 and (E)-7 along with the dioxepin 8 in a
73:21:6 ratio. Yield: 4.2 g (83%); b.p. 81 ± 828C/0.2 mmHg; anal. calcd for
6.21 (d, J ˆ 8.3, 1H), 6.11 (dm, J ˆ 16.2 Hz, 1H), 5.32 (d, J ˆ 16.2 Hz,
1H), 4.43 (d, d J ˆ 8.3 Hz, 1H), 4.20 (ddd, J ˆ 12.5, 4.2, 0.7 Hz, 1H), 3.99
(ddd, J ˆ 12.5, 8.6, 1.1 Hz, 1H), 3.90 (ddd, J ˆ 14.0, 8.6, 0.7 Hz, 1H), 3.75
(ddd, J ˆ 14.0, 4.2, 0.7 Hz, 1H), 1.98 (t, J ˆ 6.2 Hz, 2H), 1.66 (d, J ˆ 0.9 Hz,
3H),1.6 (m, 2H), 1.4 (m, 2H), 1.42 (s, 3H), 0.99 (s, 6H); MS: 263 (32%,
C13H16O2 (204.27):
C 76.44, H 7.89; found C 76.36, H 7.85. (Z)-3-
‡
‡
Benzylidene-2-dimethyl-1,4-dioxane [(Z)-7] was isolated as a pure com-
[M ‡1]), 262 (37%, [M ]), 247 (100%); anal. calcd for C17H26O2 (262.39):
C 77.82, H 9.99; found C 78.22, H 10.13%. 2-Methyl-3-methylene-2-[2-
(2,6,6-trimethylcyclohex-1-en-1-yl)-1-ethylenyl]-1,4-dioxane (4d): The by-
product was identified by gas chromatography (30 m, DB-1, 1808C; 30 m,
DB-WAX, 1808C) and its structure assigned on the basis of its character-
pound by preparative gas chromatography (6 m, 5% C-20M, 508C); nD20
ˆ
1.5526; 1H NMR: d ˆ 7.6 (m, 2H), 7.3 (m, 2H), 7.2 (m, 1H), 5.62 (s, 1H), 4.1
‡
(m, 2H), 3.9 (m, 2H), 1.52 (s, 6H); MS: 205 (100%, [M ‡1]), 204 (7%,
‡
‡
[M ]), 189 (12%, [M
15]). The structures of the two other products, (E)-
1
3-benzylidene-2,2-dimethyl-1,4-dioxane [(E)-7] and 2,3-dihydro-5,5-di-
methyl-7-phenyl-1,4-dioxepin (8), obtained by preparative gas chromatog-
raphy (see above) as a 2:1 mixture, were tentatively assigned on the basis of
istic olefinic H NMR signals: d ˆ 4.51 (d, J ˆ 1.2 Hz, 0.04H), 4.36 (d, J ˆ
1.2 Hz, 0.04H).
2,3-Dihydro-5-ethylenyl-5-methyl-1,4-dioxepin (2e) and 2-ethenyl-2-meth-
yl-3-methylene-1,4-dioxane (4e): Under the same conditions as described
for the reaction of 6, 2-[(1-ethynyl-1-methyl-2-propenyl)oxy]ethanol (1e;
3.6 mL, 3.5 g, 25 mmol) gave a 93:7 mixture of dioxepin 2e and dioxane 4e.
Yield: 2.8 g (80%); b.p. 73 ± 748C/38 mmHg; d240 ˆ 0.89; nD20 ˆ 1.4650; 1H
NMR: d ˆ 6.18 (d, J ˆ 8.5 Hz, 0.9H), 5.87 (dd, J ˆ 17.6, 10.5 Hz, 0.1H), 5.76
(dd, J ˆ 17.3, 10.4 Hz, 0.9H), 5.3 (m, 0.2H), 5.28 (dd, J ˆ 17.3, 1.5 Hz, 0.9H),
5.17 (dd, J ˆ 10.4, 1.5 Hz, 0.9H), 4.61 (d, J ˆ 1.2 Hz, 0.1H), 4.35 (d, J ˆ
8.5 Hz, 0.9H), 4.34 (d, J ˆ 1.2 Hz, 0.1H), 4.16 (ddd, J ˆ 12.6, 4.3, 1.2 Hz,
1.0H), 4.00 (ddd, J ˆ 12.6, 8.1, 1.5 Hz, 1H), 3.82 (ddd, J ˆ 14.0, 8.5, 1.2 Hz,
1H), 3.73 (ddd, J ˆ 14.0, 4.3, 1.5 Hz, 1H), 1.43 (s, 0.3H), 1.38 (s, 2.7H); MS:
1
their H NMR spectra: d ˆ 7.6 (m, 2H), 7.3 (m, 2H), 7.2 (m, 1H), 6.21 (s,
0.67H), 5.32 (s, 0.33H), 4.2 (m, 0.67H), 4.0 (m, 2H), 3.9 (m, 1.33H), 1.47 (s,
2H), 1.27 (s, 4H).
2,3-Dihydro-5,5-dimethyl-1,4-dioxepin (2a): An analogous reaction per-
formed with 2-[(1,1-dimethyl-2-propynyl)oxy]ethanol (1a; 3.4 mL, 3.2 g,
25 mmol) gave an 80:20 mixture of dioxepin 2a and dioxane 4a; yield: 2.6 g
(81%); b.p. 68 ± 708C/65 mmHg. The two components were separated by
preparative gas chromatography (6 m, 5% C-20M, 508C). Dioxepin 2a:
d240 ˆ 0.88; n2D0 ˆ 1.4475; 1H NMR: d ˆ 5.99 (d, J ˆ 8.3 Hz, 1H), 4.36 (d, J ˆ
8.3 Hz, 1H), 4.1 (m, 2H), 3.9 (m, 2H), 1.33 (s, 6H); MS: 129 (100%,
‡
‡
[M ‡1]), 128 (2%, [M ]), 118 (46%); anal. calcd for C7H12O2 (128.17): C
65.60, H 9.44; found C 65.61, H 9.47%. 2,2-Dimethyl-3-methylene-1,4-
dioxane (4a): 1H NMR: d ˆ 4.42 (d, J ˆ 1.2 Hz, 1H), 4.28 (d, J ˆ 1.2 Hz,
‡
‡
141 (1%, [M ‡1]), 140 (4%, [M ]), 126 (50%), 125 (100%); anal. calcd
for C8H12O2 (140.18): C 68.55, H 8.63; found C 68.94, H 8.64%.
‡
1H), 3.9 (m, 2H), 3.8 (m, 2H), 1.42 (s, 6H); MS: 129 (100%, [M ‡1]), 128
2,3-Dihydro-5-ethynyl-5-methyl-1,4-dioxepin (2 f): Under the same con-
ditions as described for the reaction of 6, 2-[(1-ethynyl-1-methyl-2-
propenyl)oxy]ethanol (1 f; 3.6 mL, 3.5 g, 25 mmol) gave a 73:27 mixture
of dioxepin 2 f and dioxane 4 f. Yield: 2.2 g (65%). The two isomers were
separated by column chromatography (silica gel, ethyl acetate/hexanes 1:1
‡
(3%, [M ]), 113 (56%); anal. calcd for C7H12O2 (128.17): C 65.60, H 9.44;
found C 65.56, H 9.29%.
2,3-Dihydro-5-methyl-5-phenyl-1,4-dioxepin (2b): Under the same condi-
tions as described for the reaction of 6, 2-[(1-methyl-1-phenyl-2-propyny-
l)oxy]ethanol (1b; 4.8 mL, 4.8 g, 25 mmol) gave a 91:9 mixture of dioxepin
2b and dioxane 4b. Yield: 4.1 g (86%); b.p. 69 ± 708C/0.25 mmHg. The two
components were separated by preparative gas chromatography (6 m, 5%
C-20M, 1508C). Dioxepin 2b: d240 ˆ 0.91; nD20 ˆ 1.5379; 1H NMR: d ˆ 7.5 (m,
2H), 7.3 (m, 2H), 7.2 (m, 1H), 6.27 (d, J ˆ 8.3 Hz, 1H), 4.81 (d, J ˆ 8.3 Hz,
1H), 4.11 (ddd, J ˆ 12.7, 5.2, 1.3 Hz, 1H), 4.02 (ddd, J ˆ 12.7, 7.8, 1.6 Hz,
1H), 3.77 (ddd, J ˆ 14.1, 5.2, 1.6 Hz, 1H), 3.55 (ddd, J ˆ 14.1, 7.8, 1.3 Hz,
(v/v)). Dioxepin 2 f: B.p. 50 ± 538C/20 mmHg; n2D0 ˆ 1.4727; H NMR: d ˆ
1
6.11 (d, J ˆ 7.9 Hz, 1H), 4.55 (d, J ˆ 7.9 Hz, 1H), 4.33 (ddd, J ˆ 12.9, 4.3,
1.2 Hz, 1H), 4.21 (ddd, J ˆ 13.9, 8.2, 1.2 Hz, 1H), 3.99 (ddd, J ˆ 12.9, 8.2,
1.5 Hz, 1H), 3.91 (ddd, J ˆ 13.9, 4.3, 1.5 Hz, 1H), 2.50 (s, 1H), 1.38 (s, 3H);
‡
‡
MS: 139 (1%, [M ‡1]), 138 (2%, [M ]), 105 (100%); anal. calcd for
C8H10O2 (138.17): C 69.55, H 7.29; found C 69.60, H 7.39%. 2-Ethynyl-2-
methyl-3-methylene-1,4-dioxane (4 f): b.p. 50 ± 518C/20 mmHg; nD20
ˆ
‡
‡
1.4736; 1H NMR: d ˆ 4.57 (d, J ˆ 1.6 Hz, 1H), 4.52 (d, J ˆ 1.6 Hz, 1H),
4.38 (ddd, J ˆ 14.2, 11.1, 3.1 Hz, 1H), 4.02 (ddd, J ˆ 11.1, 2.8, 1.8 Hz, 1H),
3.92 (ddd, J ˆ 14.2, 11.6, 3.1 Hz, 1H), 3.73 (ddd, J ˆ 11.6, 2.8, 1.8 Hz, 1H),
1H), 1.59 (s, 3H); MS: 191 (10%, [M ‡1]), 190 (2%, [M ]), 118 (100%);
anal. calcd for C12H14O2 (190.24): C 75.76, H 7.42; found C 75.54, H 7.35%.
2-Methyl-3-methylene-2-phenyl-1,4-dioxane (4b): 1H NMR: d ˆ 7.5 (m,
2H), 7.4 (m, 2H), 7.3 (m, 1H), 4.85 (d, J ˆ 1.2 Hz, 1H), 4.58 (d, J ˆ 1.2 Hz,
1H), 3.99 (ddd, J ˆ 12.2, 11.0, 3.4 Hz, 1H), 3.85 (ddd, J ˆ 12.2, 2.9, 2.1 Hz,
1H), 3.80 (ddd, J ˆ 11.9, 11.0, 2.9 Hz, 1H), 3.62 (ddd, J ˆ 11.9, 3.4, 2.1 Hz,
‡
‡
2.56 (s, 1H), 1.67 (s, 3H); MS: 139 (1%, [M ‡1]), 138 (2%, [M ]), 105
(100%); anal. calcd for C8H10O2 (138.17): C 69.55, H 7.29; found C 69.60, H
7.39%. Heating a mixture of 2-[(1-ethynyl-1-methyl-2-propenyl)oxy]etha-
nol (3.6 mL, 3.5 g, 25 mmol), potassium hydroxide (2.0 g, 50 mmol) and
water (25 mL) for 3 h under reflux gave an 84:16 mixture of dioxepin 2 f
and dioxane 4 f. Yield: 2.5 g (72%).
‡
‡
1H), 1.57 (s, 3H); MS: 191 (8%, [M ‡1]), 190 (53%, [M ]), 105 (100%);
anal. calcd for C12H14O2 (190.24): C 75.76, H 7.42; found C 75.71, H 7.46%.
2,3-Dihydro-5-methyl-5-(4-methyl-3-pentenyl)-1,4-dioxepin (2c): Under
the same conditions as described for the reaction of 6, 2-[(1,5-dimethyl-1-
ethynyl-4-hexenyl)oxy]ethanol (1c; 5.1 mL, 4.9 g, 25 mmol) gave an 85:15
mixture of dioxepin 2c and dioxane 4c. Yield: 4.3 g (87%). The two
components were separated by column chromatography (silica gel, ethyl
acetate/hexanes 1:6). Dioxepin 2c: b.p. 58 ±598C/0.5 mmHg; d240 ˆ 0.89;
n2D0 ˆ 1.4768; 1H NMR: d ˆ 6.04 (d, J ˆ 8.5 Hz, 1H), 5.1 (m, 1H), 4.24 (d,
J ˆ 8.5 Hz, 1H), 4.13 (ddd, J ˆ 12.5 Hz, 5.5 Hz, 1.1 Hz, 1H), 4.04 (ddd, J ˆ
12.5, 6.8, 1.1 Hz, 1H), 3.88 (ddd, J ˆ 14.2, 6.8, 1.1 Hz, 1H), 3.80 (ddd, J ˆ
14.2, 5.5, 1.1 Hz, 1H), 2.1 (m, 2H), 1.68 (d, J ˆ 1.2 Hz, 3H),1.61 (s, 1H), 1.5
Hydrolysis of dioxanes (7) and dioxepins (2):
3-Hydroxy-3-methyl-1-phenyl-2-butanone (9): A solution of 3-benzyli-
dene-2,2-dimethyl-1,4-dioxane (7; Z/E ratio ˆ 78:22; 5.1 mL, 5.1 g,
25 mmol), which also contained 6% of dioxepin 8), and 12m sulfuric acid
(20 mL) in tetrahydrofuran (0.10 L) was kept at 258C for 12 h. Water
(50 mL) was added and the product then extracted with diethyl ether (4 Â
50 mL). The combined organic layers were washed with a saturated
aqueous solution of sodium hydrogen carbonate (2 Â 50 mL) and brine
(50 mL), and then dried. After evaporation of the solvent, the residue was
distilled to give a-hydroxyketone 9. Yield: 3.4 g (76%); b.p. 96 ± 998C/
0.02 mmHg; (ref. [14]: b.p. 1008C/0.05 mmHg); n2D0 ˆ 1.5454; 1H NMR: d ˆ
7.3 (m, 5H), 3.87 (s, 2H), 1.8 (brs, 1H), 1.43 (s, 6H).
‡
‡
(m, 2H), 1.28 (s, 3H); MS: 197 (19%, [M ‡1]), 196 (2%, [M ]), 119
(100%); anal. calcd for C12H20O2 (196.29): C 73.43, H 10.27; found C 73.29,
H
10.07%. 3-Methyl-3-methylene-2-(4-methyl-3-pentenyl)-1,4-dioxane
(4c): b.p. 59 ± 608C/0.5 mmHg; n2D0 ˆ 1.4723; 1H NMR: d ˆ 5.1 (m, 1H),
4.46 (d, J ˆ 1.4 Hz, 1H), 4.23 (d, J ˆ 1.4 Hz, 1H), 2.9 (m, 3H), 3.7 (m, 1H),
2.0 (m, 2H), 1.9 (m, 1H), 1.68 (d, J ˆ 0.9 Hz, 3H), 1.7 (m, 1H), 1.61 (brs,
3-Methyl-3-butenal (3a): A solution of 2,3-dihydro-5-dimethyl-1,4-dioxe-
pin (2a; 3.6 mL, 3.2 g, 25 mmol) and 6m hydrochloric acid (20 mL) in
tetrahydrofuran (0.10 L) was heated under reflux for 5 h. Water (50 mL)
was added and the product was then extracted with diethyl ether (4 Â
50 mL). The combined organic layers were washed with a saturated
aqueous solution of sodium hydrogen carbonate (2 Â 50 mL) and brine
(50 mL), and then dried. Distillation afforded the a,b-unsaturated alde-
hyde 3a. Yield: 0.95 g (45%); b.p. 75 ± 778C/70 mmHg (ref. [15]: b.p. 130 ±
1358C); n2D0 ˆ 1.4550 (ref. [15]: n2D0 ˆ 1.4550); 1H NMR: d ˆ 9.96 (d, J ˆ
8.2 Hz, 1H), 5.89 (dm, J ˆ 8.2 Hz, 1H), 2.17 (d, J ˆ 1.2 Hz, 3H), 1.99 (d,
J ˆ 1.1 Hz, 3H).
‡
‡
3H), 1.36 (s, 3H); MS: 197 (17%, [M ‡1]), 196 (1%, [M ]), 119 (100%);
anal. calcd for C12H20O2 (196.29): C 73.43, H 10.27; found C 73.33, H
10.11%.
2,3-Dihydro-5-methyl-5-[2-(2,6,6-trimethylcyclohexenyl)ethenyl]-1,4-diox-
epin (2d): Under the same conditions as described for the reaction of 6, 2-
[[1-ethynyl-1-methyl-3-(2,6,6-trimethylcyclohexenyl)-2-propenyl]oxy]etha-
nol (1d; 6.3 mL, 6.5 g, 25 mmol) gave a 96:4 mixture of 2d and 4d. Yield:
7.2 g (79%); b.p. 85 ± 878C/0.02 mmHg; d240 ˆ 0.90; nD20 ˆ 1.4706. No sepa-
ration of the two isomers was achieved. Dioxepin 2d: 1H NMR: d ˆ
Chem. Eur. J. 1998, 4, No. 9
ꢁ WILEY-VCH Verlag GmbH, D-69451 Weinheim, 1998
0947-6539/98/0409-1741 $ 17.50+.25/0
1741

M. Schlosser and H.-x. Wei
FULL PAPER
‡
‡
‡
(E)-3-Phenyl-2-butenal (3b): From 2,3-dihydro-5-methyl-5-phenyl-1,4-di-
oxepin (2b; 5.2 mL, 4.8 g, 25 mmol), as described for the hydrolysis of
dioxepin 2a, as a 1:3 Z/E mixture according to gas chromatography (30 m,
DB-1, 1008C; 5 m, 5% C-20M, 1508C). Yield: 2.4 g (65%); b.p. 75 ± 778C/
[M ‡1]), 326 (15%, [M ]), 311 (14%, [M
15]), 113 (100%); anal. calcd
for C22H30O2 (326.48): C 80.94, H 9.26; found C, 81.10 H 9.36%.
[2(Z),6(E),8(E)]-3,7-Dimethyl-9-(2,6,6-trimethylcyclohexenyl)-2,6,8-non-
atrien-4-ynal (12):[25, 26] A solution of 6m hydrochloric acid (20 mL) and
dioxepin 11 (8.5 mL, 8.2 g, 25 mmol) in tetrahydrofuran (0.10 L) was kept
under nitrogen for 16 h at 258C. Then diethyl ether (0.10 L) and water
(50 mL) were added. The organic layer was washed with an aqueous
solution of saturated sodium hydrogencarbonate (2 Â 50 mL) and brine
(50 mL), and then dried. After evaporation of the solvent, the residue was
purified by chromatography (neutral aluminum oxide, ethyl acetate/
0.5 mmHg (ref. [16]: b.p. 79 ± 848C/0.1 mmHg); n2D0 ˆ 1.5866 (ref. [16]: n2D0
ˆ
1.5861).
(E)-3,7-Dimethyl-2,6-octadienal (3c): From 2,3-dihydro-5-methyl-5-(4-
methyl-3-pentenyl)-1,4-dioxepin (2c; 5.5 mL, 4.9 g, 25 mmol), as described
for the hydrolysis of dioxepin 2a, as a 1:2 Z/E mixture according to gas
chromatography (30 m, DB-1, 1008C; 30 m, DB-WAX, 1208C). Yield: 1.5 g
(40%); b.p. 58 ± 608C/1 mmHg (ref. [17]: b.p. 53 ± 548C/0.05 mmHg); nD20
1.4870 (ref. [18]: n2D0 ˆ 1.4874).
ˆ
hexanes 1:10 (v/v)) to give
a yellow oil which, according to gas
chromatography (30 m, DB-1, 2008C; 30 m, DB-WAX, 2008C), contained
the [2(Z),6(E),8(E)] and (2(E),6(E),8(E)] isomers in a 4:1 ratio. Yield:
(2(E),4(E))-3-Methyl-5-(2,6,6-trimethylcyclohex-1-enyl)pent-2,4-dien-1-al
(3d): From 2,3-dihydro-5-methyl-5-[2-(2,6,6-trimethylcyclohexenyl)ethen-
yl]-1,4-dioxepin (2d; 7.3 mL, 6.6 g, 25 mmol), as described for the
hydrolysis of dioxepin 2a, as a 1:3 2(Z),4(E)/2(E),4(E) mixture according
to gas chromatography (30 m, DB-1, 1808C; 30 m, DB-WAX, 1808C).
Yield: 4.9 g (90%); b.p. 95 ± 988C/0.05 mmHg (ref. [19]: b.p. 90 ± 958C/
0.01 mmHg); n2D0 ˆ 1.5765 (ref. [19]: n2D0 ˆ 1.5780).
4.4 g (62%); n2D0 ˆ 1.6094; H NMR: d ˆ 10.08 (d, J ˆ 8.3 Hz, 0.8H), 10.04
1
(d, J ˆ 8.3 Hz, 0.2H), 6.39 (dm, J ˆ 16.2 Hz, 1H), 6.16 (d, J ˆ 16.2 Hz, 1H),
6.12 (dm, J ˆ 8.3 Hz, 1H), 5.62 (brs, 0.8H), 5.60 (brs, 0.2H), 2.35 (d, J ˆ
1.5 Hz, 0.6H), 2.17 (d, J ˆ 1.2 Hz, 2.4H), 2.11 (d, J ˆ 1.4 Hz, 0.6H), 2.13 (d,
J ˆ 0.8 Hz, 3H), 2.0 (m, 2H), 1.71 (d, J ˆ 0.7 Hz, 2.4H), 1.6 (m, 2H), 1.5 (m,
2H), 1.02 (s, 6H).
(E)-3-Methyl-2,4-pentadienal (3e): From 2,3-dihydro-5-ethylenyl-5-meth-
yl-1,4-dioxepin (2e containing 7% of dioxane 4e) (3.9 mL, 3.5 g, 25 mmol),
as described for the hydrolysis of dioxepin 2a, as a 1:2 Z/E mixture
according to gas chromatography (30 m, DB-1, 608C; 30 m, DB-WAX,
608C). Yield: 1.0 g (45%); b.p. 54 ± 568C/12 mmHg (ref. [20]: b.p. 51 ±
528C/12 mmHg); nD20 ˆ 1.5205 (ref. [20]: n2D0 ˆ 1.5220).
Acknowledgments: The authors are indebted to the Schweizerische
Nationalfonds zur Förderung der wissenschaftlichen Forschung (grant 20-
49ꢀ307-96), Bern, and Hoffmann ± LaRoche, Basel (Switzerland), for
financial support.
Received: February 18, 1998 [F1013]
(Z)-3-Methyl-2-penten-4-ynal (3 f): From 2,3-dihydro-5-ethynyl-5-methyl-
1,4-dioxepin (2 f) (3.8 mL, 3.5 g, 25 mmol), as described for the hydrolysis
of dioxepin 2a, as a 7:1 Z/E mixture according to gas chromatography (5 m,
5% SE-30, 708C; 5 m, 5% C-20M, 708C). Yield: 1.2 g (50%); b.p. 47 ±
508C/20 mmHg (ref. [21]: b.p. 40 ± 448C/14 mmHg); n2D0 ˆ 1.4985 (ref. [22]:
n2D0 ˆ 1.4970).
[1] V. Jäger, H. G. Viehe, in Houben-Weyl: Methoden der organischen
Chemie, Vol. 5/2a (Ed.: E. Müller), Thieme, Stuttgart, 1977, pp. 726 ±
737; G. A. Olah, D. Meidar, Synthesis 1978, 671 ± 672; see also the
related Rupe isomerization: H. Rupe, W. Messner, E. Kambli, Helv.
Chim. Acta 1928, 11, 449 ± 462; H. Rupe, F. Kuenzy, Helv. Chim. Acta
1931, 14, 708 ± 718.
[2] H. Pauling, D. A. Andrews, N. C. Hindley, Helv. Chim. Acta 1976, 59,
1233 ± 1243; see also P. Chabredes, E. Kuntz, J. Varagnat, Tetrahedron
1977, 33, 1775 ± 1783; P. Chabardes, Tetrahedron Lett. 1988, 29, 6253 ±
6256; C. Y. Lorber, J. A. Osborn, Tetrahedron Lett. 1996, 37, 853 ± 856;
M. Picquet, C. Bruneau, P. H. Dixneuf, J. Chem. Soc. Chem. Commun.
1997, 1201 ± 1202.
[3] Working procedure: M. Schlosser in Organometallics in Synthesis: A
Manual (Ed.: M. Schlosser), Wiley, Chichester, 1994, p. 126.
[4] K. S. Y. Lau, M. Schlosser, J. Org. Chem. 1978, 43, 1595 ± 1598; M.
Schlosser, H.-x. Wei, Tetrahedron 1997, 53, 1735 ± 1742. The final
hydrolysis, unless performed under ultrafast stirring or ultrasound
irradiation, should require over 2 h (rather than 15 min).
[5] M. F. Shostakovskii, B. A. Trofimov, A. S. Atavin, V. I. Lavrov, Russ.
Chem. Rev. 1968, 37, 907 ± 919; V. Jäger, H. G. Viehe, in Houben-Weyl:
Methoden der organischen Chemie, Vol. 5/2a (Ed.: E. Müller), Thieme,
Stuttgart, 1977, pp. 738 ± 740; see also the related Meyer ± Schuster
isomerization: K. H. Meyer, K. Schuster, Ber. Dtsch. Chem. Ges. 1922,
55, 819 ± 823; for the addition of thiols to unactivated triple bonds, see
also: O. Ruel, E. Guittet, S. Julia, Tetrahedron Lett. 1983, 24, 61 ± 64;
11,12-Dehydroretinal
2,3-Dihydro-5-[4(E)]-3-hydroxy-4-methyl-6-(2,6,6-trimethylcyclohexen-
yl)-4-hexen-1-ynyl]-5-methyl-1,4-dioxepin (10): Butyllithium (25 mmol) in
hexane (17 mL) and 2-methyl-4-(2,6,6-trimethylcyclohexenyl)-2-butenal[23]
(5.5 mL, 5.2 g, 25 mmol) were added consecutively to a solution of 2,3-
dihydro-5-ethynyl-5-methyl-1,4-dioxepin (2 f; 3.8 mL, 3.5 g, 25 mmol) in
tetrahydrofuran (0.10 L) cooled to
758C. After 1 h at 258C, ethanol
(10 mL) was added. The mixture was absorbed on silica gel (10 mL) and
eluted from a column filled with more silica gel (200 mL) (ethyl acetate/
hexanes 1:4 (v/v)) to afford a 1:2 diastereomeric mixture. Yield: 7.8 g
(91%); anal. calcd for C22H32O3 (344.49): C 76.70, H 9.36; found C 76.74, H
9.11%. Minor diastereoisomer (isolated from the first chromatographic
fractions): n2D0 ˆ 1.4995; 2.6 g (30%); 1H NMR: d ˆ 6.05 (d, J ˆ 8.0 Hz, 1H),
5.47 (t, J ˆ 6.5 Hz, 1H), 4.77 (d, J ˆ 5.5 Hz, 1H), 4.53 (d, J ˆ 8.0 Hz, 1H),
4.30 (ddm, J ˆ 12.8, 4.6 Hz, 1H), 4.16 (ddm, J ˆ 13.8, 8.3 Hz, 1H), 3.97
(ddm, J ˆ 12.8, 8.3 Hz, 1H), 3.85 (ddm, J ˆ 13.8, 4.6 Hz, 1H), 2.74 (d, J ˆ
6.5 Hz, 2H), 1.91 (brt, J ˆ 6.3 Hz, 2H), 1.80 (s, 3H), 1.61 (s, 3H), 1.6 (m,
2H), 1.57 (s, 3H), 1.4 (m, 2H), 0.97 (s, 3H), 0.96 (s, 3H); MS: 345 (1%,
‡
[M ‡1]), 279 (4%), 207 (6%), 123 (100%). Major diastereoisomer
(isolated from the later chromatographic fractions): n2D0 ˆ 1.5041; 5.2 g
1
(61%); H NMR: d ˆˆ 6.05 (d, J ˆ 7.9 Hz, 1H), 5.46 (t, J ˆ 6.5 Hz, 1H),
4.77 (d, J ˆ 5.5 Hz, 1H), 4.53 (d, J ˆ 7.9 Hz, 1H), 4.30 (ddm, J ˆ 12.6, 4.7 Hz,
1H), 4.16 (ddm, J ˆ 13.9, 8.2 Hz, 1H), 3.97 (ddm, J ˆ 12.6, 8.2 Hz, 1H), 3.85
(ddm, J ˆ 13.9, 4.7 Hz, 1H), 2.74 (d, J ˆ 6.5 Hz, 2H), 1.91 (brt, J ˆ 6.3 Hz,
2H), 1.80 (s, 3H), 1.6 (m, 2H), 1.57 (s, 3H), 1.53 (s, 3H), 1.4 (m, 2H), 0.97 (s,
Á
M. Julia, C. Lefebvre, Tetrahedron Lett. 1984, 25, 189 ± 192.
[6] A. T. Bottini, J. G. Maroski, J. Org. Chem. 1973, 38, 1455 ± 1462; see
also: R. Faure, G. Descotes, Bull. Soc. Chim. Fr. 1966, 1569 ± 1575.
[7] H. A. Skinner, A. Snelson, Trans. Faraday Soc. 1959, 55, 404 ± 407; see
also: J. L. H. Allan, M. C. Whiting, J. Chem. Soc. 1953, 3314 ± 3316.
[8] R. Ruzziconi, M. Schlosser, Angew. Chem. 1982, 94, 865 ± 866; Angew.
Chem. Int. Ed. Engl. 1982, 21, 855 ± 856; Angew. Chem. Suppl. 1982,
1853 ± 1864.
[9] O. Isler, W. Huber, A. Ronco, M. Kofler, Helv. Chim. Acta 1947, 30,
1911 ± 1927; O. Isler, A. Ronco, W. Guex, N. C. Hindley, W. Huber, K.
Dialer, M. Kofler, Helv. Chim. Acta 1949, 32, 489 ± 505.
[10] O. Desponds, L. Franzini, M. Schlosser, Synthesis 1997, 150 ± 152.
[11] A. Matijoska, A. Ceika, A. Mozolis, S. Plevokas, Liet. TSR Mokslu
Akad. Darb. Ser. B 1982, 2, 27 ± 37; Chem. Abstr. 1982, 97, 55260t.
[12] W. Gerhardt, R. Lehmann, Ger. Offen. DE 3216894 (application: May
6, 1982, to Henkel KG); Chem. Abstr. 1984, 100, 67830x.
‡
‡
3H), 0.96 (s, 3H); MS: 345 (9%, [M ‡1]), 344 (11%, [M ]), 329 (15%,
‡
[M
15]), 327 (100%).
[3(E),5(E)]-2,3-Dihydro-5-methyl-5-[(4-methyl-6-(2,6,6-trimethylcyclo-
hexenyl)-3,5-hexadien-1-ynyl]-1,4-dioxepin (11): (Methoxycarbonylsulfa-
moyl)triethylammonium hydroxide[24] (11.9 g, 50 mmol) and the hydroxy-
lated dioxepin 10 (8.6 mL, 8.6 g, 25 mmol) were dissolved in toluene
(0.10 L). After heating to 808C for 6 h, the mixture was absorbed on silica
gel (10 mL). Column chromatography (ethyl acetate/hexanes 1:10 (v/v))
afforded a yellow oil. Yield: 5.3 g (65%); n2D0 ˆ 1.5527; H NMR: d ˆ 6.24
1
(brd, J ˆ 16.0 Hz, 1H), 6.08 (d, J ˆ 16.0 Hz, 1H), 6.07 (d, J ˆ 8.0 Hz, 1H),
5.44 (brs, 1H), 4.61 (d, J ˆ 8.0 Hz, 1H), 4.34 (ddm, J ˆ 12.8, 4.6 Hz, 1H),
4.24 (ddm, J ˆ 14.2, 8.2 Hz, 1H), 4.00 (ddd, J ˆ 12.8, 8.2, 1.4 Hz, 1H), 3.88
(ddd, J ˆ 14.2, 4.6, 1.4 Hz, 1H), 2.04 (s, 3H), 2.00 (brt, J ˆ 6.3 Hz, 2H,), 1.68
(s, 3H), 1.63 (s, 3H), 1.6 (m, 2H), 1.4 (m, 2H), 1.00 (s, 6H); MS: 327 (70%,
[13] E. E. Boehm, M. C. Whiting, J. Chem. Soc. 1963, 2541 ± 2543.
1742
ꢁ WILEY-VCH Verlag GmbH, D-69451 Weinheim, 1998
0947-6539/98/0409-1742 $ 17.50+.50/0
Chem. Eur. J. 1998, 4, No. 9

Aldehyde Synthesis
1738±1743
[14] R. Ramage, G. J. Griffiths, F. E. Shutt, J. Chem. Soc. Perkin Trans. I
1984, 1531 ± 1537.
[15] N. L. Wendler, H. L. Slates, J. Am. Chem. Soc. 1950, 72, 5341.
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[17] G. Saucy, R. Marbet, H. Lindlar, O. Isler, Helv. Chim. Acta 1959, 42,
1945 ± 1955.
[18] M. A. Schwartz, G. C. Swanson, J. Org. Chem. 1979, 44, 953 ± 958.
[19] N. L. Wendler, H. L. Slates, N. R. Trenner, M. Tishler, J. Am. Chem.
Soc. 1951, 73, 719 ± 724.
[21] M. Montavon, H. Lindlar, R. Marbet, R. Rüegg, G. Ryser, G. Saucy, P.
Zeller, O. Isler, Helv. Chim. Acta 1957, 40, 1250 ± 1256.
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2540.
[23] H. Oediger, K. Eiter, Chem. Ber. 1964, 97, 549 ± 566.
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31.
[25] P. A. Bütikofer, C. H. Eugster, Helv. Chim. Acta 1983, 1148 ± 1174.
Â
[26] J. L. Olive, M. Mousseron-Canet, J. Dornand, Bull. Soc. Chim. Fr.
[20] P. Gramatica, P. Manitto, D. Monti, G. Speranza, Tetrahedron 1988, 44,
1299 ± 1304.
1969, 3247 ± 3252.
Chem. Eur. J. 1998, 4, No. 9
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