Base mediated aromatization of carbonyl condensation products derived from 2-(2-bromoprop-2-enyl)cyclohexanone derivatives via 'Intramolecular Unsaturation Transfer'

Article abstract of DOI:10.1002/hlca.200890124

Alkylbenzenes are synthesized for the first time from aliphatic hydrocarbons via an one pot, transition metal-free coupling approach under basic conditions. The method consists of two steps: condensation of 2-bromoprop-2-enyl- or 2-propargylcyclohexanone with alcohols, amines, or amino alcohols, followed by base treatment (Scheme 1). Phenolic ethers and N-phenylated polyalkyl aromatic compounds are shown to be in the scope of the demonstrated reaction (Table). The proposed mechanism suggests that the unsaturation in another part of the molecule (propargyl-group equivalent) is transferred into the cyclohexane ring to yield a benzene ring through a series of prototropic shifts.

Full text of DOI:10.1002/hlca.200890124

1148
Helvetica Chimica Acta – Vol. 91 (2008)
Base Mediated Aromatization of Carbonyl Condensation Products Derived
from 2-(2-Bromoprop-2-enyl)cyclohexanone Derivatives via ꢀIntramolecular
Unsaturation Transferꢁ
a
b
a
˙
by Emre Y. Yazıcıog˘lu ), Idris M. Akhmedov ), and Cihangir Tanyeli* )
a) Department of Chemistry, Middle East Technical University, 06531 Ankara, Turkey
(phone: þ 903122103222; fax: þ 903122103200; e-mail: tanyeli@metu.edu.tr)
b) Z. Khalilov 23, Baku State University, 370148 Baku, Azerbaijan
Alkylbenzenes are synthesized for the first time from aliphatic hydrocarbons via an one pot,
transition metal-free coupling approach under basic conditions. The method consists of two steps:
condensation of 2-bromoprop-2-enyl- or 2-propargylcyclohexanone with alcohols, amines, or amino
alcohols, followed by base treatment (Scheme 1). Phenolic ethers and N-phenylated polyalkyl aromatic
compounds are shown to be in the scope of the demonstrated reaction (Table). The proposed mechanism
suggests that the unsaturation in another part of the molecule (propargyl-group equivalent) is
transferred into the cyclohexane ring to yield a benzene ring through a series of prototropic shifts.
Introduction. – Despite comprising a major portion of all organic compounds,
synthetic procedures for the preparation of molecules containing benzene ring(s) are
mainly dependent on modifications of benzene derivatives [1]. Alternative methods
described in the literature include oxidative, radical, or transition metal mediated
dehydrogenation of cyclohexane derivatives [2], direct construction of a benzene ring
via intramolecular cyclization or cycloaddition [3], and biotransformations [4].
Recently, in a study on the synthesis of tetrahydroindole derivatives [5a], we
t
discovered that, when treated with BuOK, oxazolidines and acetals derived from 2-
(2-bromoprop-2-enyl)cyclohexanone [5a][5b] yielded an aromatized product, in which
the cyclohexane ring was converted to a benzene ring, whereas the 2-bromoprop-2-enyl
moiety was transformed into a Pr group (Scheme 1). In this report, we present the
preliminary results on our research of the mechanism, synthetic utility, and scope of this
particular transformation.
Scheme 1. Aromatization via Intamolecular Unsaturation Transfer
ꢀ 2008 Verlag Helvetica Chimica Acta AG, Zürich

Helvetica Chimica Acta – Vol. 91 (2008)
1149
Results and Discussion. – In the Table, a number of aromatization products
obtained by the process described above are listed, and it is shown that the method is
applicable to 1,2-amino alcohols, diol, primary alcohol, and amine structures to yield N-
alkyl-2-propylanilines or corresponding phenol ethers and gives important clues about
both the scope and mechanism of this reaction.
It is well documented in the literature that chiral 1,2-amino alcohols can act as
ligands in catalytic asymmetric organozinc additions [6] and boron-catalyzed reactions,
and serve as building blocks in the synthesis of biologically active compounds [7][8].
Moreover, it is very likely that the synthesized compounds may serve as valuable chiral
ligands or may be starting materials for biologically active targets. There are also
procedures available for different kinds of modifications on Pr groups attached to a
phenyl unit [9]. Phenolic ethers, which are available via our methodology, may also be
used as starting materials for several biologically active products [10].
In Entries 12 and 13, it is observed that a Me group present in the starting material
1c remains in the aromatized product, which clearly indicates that alkyl-substituted
benzene derivatives are also available via our methodology. The substrates for
aromatization products are prepared from readily available, cheap cyclohexanone
derivatives; are easily obtained via various Stork-enamine species; and are converted to
valuable N-alkylphenylated compounds in one step without the inclusion of any
transition metal compounds. All these data together indicate that, under optimized
conditions for each target, this aromatization reaction can provide valuable shortcuts in
organic synthesis.
The most important information that allows us to propose a mechanism for this
reaction is the unsaturation of the cyclohexane moiety to yield a benzene ring and the
saturation of the 2-bromoprop-2-enyl group to a propane entity, which strongly
indicates an ꢁintramolecular unsaturation transferꢂ from the 2-bromoprop-2-enyl moiety
to a cyclohexane ring. Entry 5 in the Table, in which a propargyl unit has replaced the 2-
bromoprop-2-enyl unit, also underwent an aromatization reaction and this strongly
excludes the possibility of a radical reaction mechanism because there is no reasonable
candidate of a radical source in this case. This prompted us to propose a reaction
mechanism that proceeded through ionic intermediates. KOH, 4-(dimethylamino)pyri-
dine, and 1,8-diazabicyclo[5.4.0]undec-7-ene were also screened as base instead of
tBuOK with the same stoichiometry, but failed to yield any aromatized product. In
Scheme 2, the reaction mechanism is outlined, and an imine is selected as a model
condensation product1). According to our mechanistic model, two C¼C bonds of the
benzene ring are provided by the unsaturation in the 2-bromoprop-2-enyl moiety,
whereas the third C¼C bond, which completes the transformation to a benzene ring, is
provided by the functional group (oxazolidine, acetal, imine), which has replaced the
C¼O O-atom in the starting ketone. The driving force for this reaction may be the
isomerization under these ꢁforcedꢂ reaction conditions, which ultimately gave the final
1
)
For amino alcohols, the question of ꢁwhich intermediate, imine or oxazolidine yields the aromatized
productꢂ may arise at this point. It is reported that these two species are in tautomeric equilibrium
with each other for different C¼O compounds [11]. Both compounds can be converted to the same
enamine species under reaction conditions. Acetals will similarly yield enol ethers under the same
conditions and provide the third C¼C bond to complete the aromatization.

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Helvetica Chimica Acta – Vol. 91 (2008)
Scheme 2. Proposed Reaction Mechanism by Consecutive Prototropic Shifts
(and probably the most stable under the reaction conditions) aromatized product,
which is not further converted to any other product.
Another evidence for the proposed reaction mechanism comes from a designed
experiment, in which the cyclohexanone ring was ꢁblockedꢂ for aromatization by
replacing two H-atoms by Me groups (Scheme 3). 4,4-Dimethyl-2-(prop-2-yn-1-
yl)cyclohexanone 13 was treated with triethyl orthoformate and EtOH to yield 1-
ethoxy-4,4-dimethyl-6-(prop-2-yn-1-yl)cyclohexene (14). When 14 was subjected to
the aromatization conditions, a structure resembling to proposed intermediates, (6E)-
1-ethoxy-4,4-dimethyl-6-(prop-2-en-1-ylidene)cyclohexene (15) was isolated as ex-
pected.
In conclusion, we have demonstrated a new coupling method for the synthesis of
substituted benzene rings. This study, which concentrated on the establishment of scope
and mechanism of the presented aromatization reaction, may be extended to further
targets by optimizing the conditions for higher yields, which may provide a new and
useful method for synthetic applications. We are planning to use the chiral products
obtained as ligands in asymmetric synthesis, to modify the propyl group by alternating
the side chain in the starting ketone, and to use our method to synthesize benzolactam
V-8 [12].

Helvetica Chimica Acta – Vol. 91 (2008)
1151
Table. Aromatization of Various Condensation Products
Entry
1
Substrate
RꢀZꢀH
Product
Yield [%]a)
35
1a
1
2
1a
2
33
3
4
1a
1a
3
4
22
56
5
6
7
1bb)
1a
4
5
6
42
30
45
1a
8
9
1a
1a
7
8
31
12
10
1a
1a
9
45
30
11c)
10

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Helvetica Chimica Acta – Vol. 91 (2008)
Table (cont.)
Entry
12
Substrate
RꢀZꢀH
Product
Yield [%]a)
34
1c
11
13
14
1c
1a
12
37
No reaction
–
a) Yields after chromatography. b) For synthesis, see [5c]. c) The synthetic procedure is different from
outlined above, see Exper. Part.
Scheme 3
:
This work was made possible by a grant from TÜBITAK TBAG-105T247 and ODTÜ BAP-2006-07-
02-00-01. We thank Murat Kaya for FT-IR spectra.
Experimental Part
1. General. Reactions were monitored by TLC after a ꢁminiꢂ workup of the reaction mixture, using
precoated SiO2 plates (Merck silica gel 60 F-254), visualized by UV light and phosphomolybdic acid in
EtOH. For purification of crude mixtures, flash chromatography (FC) was applied using SiO2 (J. T. Baker
0.063 – 0.200 mm). Polarimetric measurements: Rudolph Scientific Autopol III polarimeter and reported
as follows [a]2D0 (c in g per 100 ml, solvent). IR Spectra: Digilab Excalibur Series FT-IR. 1H- and
13C-NMR Spectra: in CDCl3, on a Bruker Spectrospin Avance DPX 400 spectrometer (400 MHz for 1H
and 100 MHz for 13C); chemical shifts with respect to Me4Si (1H, 0.00 ppm) or CDCl3 (13C, 77.1 ppm).
HR-MS Data: LC-MS analysis: APCI-Q-TOF II (Waters, Milford, MA, USA) at the Mass Spectrometry
Facility Center for Functional Genomics University at Albany.
2. Starting Materials. All commercially available chemicals were purchased from Aldrich Chemicals.
Substrates are distilled prior to use. Dimethyl sulfoxide (DMSO) was dried over CaH2 prior to use.
3. Synthesis of Aromatized Products 1 – 12. Products 1 – 12 were obtained by the procedure described
for 1. (2S)-3-Methyl-2-[(2-propylphenyl)amino]butan-1-ol (1). 1 equiv. of 2-(2-bromoprop-2-enyl)cy-

Helvetica Chimica Acta – Vol. 91 (2008)
1153
clohexanone (0.31 g, 1.43 mmol) was mixed with 1.5 equiv. of (S)-valinol (0.22 g, 2.15 mmol) and 10 mg
of TsOH in dry toluene (30 ml). The mixture was heated under reflux for 6 h, toluene was evaporated in
t
vacuo, and dry DMSO (5 ml) and BuOK (0.32 g, 2.86 mmol) were added. The reaction mixture was
immersed in an oil bath at 808 and agitated for a further 3 h with a magnetic stirrer, and purified by FC
without workup to yield a yellow-brown oil, 1 (0.11 g, 35% yield). [a]2D5 ¼ ꢀ10.03 (c ¼ 1.5, CHCl3). IR
1
(CCl4): 3424, 2960, 2931, 2873, 1605, 1586, 1507, 1455, 1310, 1251, 1164. H-NMR: 0.83 – 0.96 (m, 9 H);
1.59 (sext, J ¼ 7.3, 2 H); 1.78 – 1.92 (m, 2 H); 2.40 (t, J ¼ 6.2, 2 H); 3.32 (t, J ¼ 6.2, 1 H); 3.50 – 3.54 (m,
2 H); 3.70 (dd, J ¼ 6.7, 4.2, 1 H); 6.58 – 6.64 (m, 2 H); 6.97 – 7.04 (m, 2 H). 13C-NMR: 145.9; 129.8; 127.5;
126.8; 117.5; 111.6; 62.9; 60.7; 37.1; 30.4; 22.2; 19.5; 14.7. HR-CI-MS: 222.1867 ([M þ H]þ, C14H24NOþ;
calc. 222.1858).
N-(4,4-Diethoxybutyl)-2-propylaniline (2): Yellow oil, 33% yield. IR (CCl4): 3491, 2872, 2358, 1558,
1510, 1133. 1H-NMR: 0.92 (t, J ¼ 7.3, 3 H); 1.12 (t, J ¼ 8.5, 6 H); 1.57 (sext, J ¼ 7.6, 2 H); 1.66 (br. s, 4 H);
2.35 (t, J ¼ 7.7, 2 H); 3.10 (br. s, 2 H); 3.39 – 3.47 (m, 2 H); 3.55 – 3.62 (m, 2 H); 4.47 (br. s, 1 H); 6.10 (d,
J ¼ 8.0, 1 H); 6.59 (t, J ¼ 7.4, 1 H); 6.96 (d, J ¼ 7.3, 1 H); 7.04 (t, J ¼ 7.6, 1 H). 13C-NMR: 146.2; 129.4;
127.6; 126.5; 117.1; 110.5; 103.1; 61.6; 44.2; 33.7; 31.7; 25.2; 20.0; 15.8; 14.7. HR-CI-MS: 280.2287 ([M þ
H]þ, C17H30NOþ2 ; calc. 280.2277).
2-[(2-Propylphenyl)amino]ethanol (3). Yellow oil, 22% yield. IR (CCl4): 3413, 2958, 2927, 2873,
2353, 1697, 1605, 1507, 1452, 1310, 1256, 1052. 1H-NMR: 0.92 (t, J ¼ 7.3, 3 H); 1.56 – 1.65 (m, 2 H); 2.39 (t,
J ¼ 7.7, 2 H); 3.24 (t, J ¼ 5.3, 2 H); 3.76 (t, J ¼ 5.3, 2 H); 6.58 (d, J ¼ 8.0, 1 H); 6.63 (t, J ¼ 7.4, 1 H); 6.97 (d,
J ¼ 7.4, 1 H); 7.01 – 7.06 (m, 1 H). 13C-NMR: 144.6; 128.2; 126.0; 125.9; 116.6; 109.7; 60.2; 45.2; 32.2; 20.7;
13.2. HR-CI-MS: 180.1383 ([M þ H]þ, C11H18NOþ; calc. 180.1388).
(2R)-2-[(2-Propylphenyl)amino]butan-1-ol (4). Yellow oil, 56% yield. [a]2D5 ¼ þ22.05 (c ¼ 1.1,
CHCl3). IR (CCl4): 3425, 2965, 2933, 2874, 2352, 1698, 1605, 1586, 1510, 1454, 1311, 1245, 1058, 913.
1H-NMR: 0.88 – 0.95 (m, 6 H); 1.48 – 1.65 (m, 4 H); 2.39 (t, J ¼ 7.7, 2 H); 3.37 – 3.43 (m, 1 H); 3.50 (dd,
J ¼ 10.9, 5.6, 1 H); 6.60 – 6.63 (m, 2 H); 6.97 – 7.05 (m, 2 H). 13C-NMR: 145.2; 129.4; 127.1; 126.7; 117.3;
111.2; 64.0; 56.4; 33.3; 25.0; 21.8; 14.3; 10.6. HR-CI-MS: 208.1715 ([M þ H]þ, C13H22NOþ; calc.
208.1701).
(2R)-1-[(2-Propylphenyl)amino]propan-2-ol (5). Brown oil, 30% yield. [a]2D5 ¼ ꢀ4.76 (c ¼ 0.7,
CHCl3). IR (CCl4): 3426, 2965, 2932, 2873, 2352, 1698, 1606, 1586, 1510, 1455, 1378, 1311, 1129, 1010, 908.
1H-NMR: 0.93 (t, J ¼ 7.3, 3 H); 1.20 (d, J ¼ 6.2, 3 H); 1.58 (sext, J ¼ 7.5, 2 H); 2.40 (t, J ¼ 7.7, 2 H); 2.95 (dd,
J ¼ 12.8, 4.3, 1 H); 3.19 (dd, J ¼ 12.8, 3.4, 1 H); 3.95 – 4.03 (m, 1 H); 6.58 (d, J ¼ 8.1, 1 H); 6.63 (t, J ¼ 7.4,
1 H); 6.97 (d, J ¼ 7.4, 1 H); 7.02 – 7.06 (m, 1 H). 13C-NMR: 144.7; 128.2; 126.0; 125.9; 116.6; 109.7; 65.4;
50.8; 32.3; 20.8; 20.0; 13.2. HR-CI-MS: 194.1550 ([M þ H]þ, C12H20NOþ; calc. 194.1545).
(2R)-2-[(2-Propylphenyl)amino]propan-1-ol (6). Yellow oil, 45% yield. [a]2D5 ¼ ꢀ1.99 (c ¼ 0.2,
CHCl3). IR (CCl4): 3420, 2962, 2932, 2873, 1605, 1586, 1507, 1455, 1310, 1165, 998. 1H-NMR: 0.92 (t, J ¼
7.3, 3 H); 1.12 (d, J ¼ 6.4, 3 H); 1.51 – 1.62 (m, 2 H); 2.37 (t, J ¼ 7.7, 2 H); 3.44 – 3.49 (m, 1 H); 3.57 – 3.64
(m, 2 H); 6.68 – 6.73 (m, 2 H); 6.99 – 7.21 (m, 2 H). 13C-NMR: 143.9; 128.4; 126.0; 116.6; 110.5; 65.2; 49.6;
32.3; 20.8; 16.7; 13.2. HR-CI-MS: 194.154 ([M þ H]þ, C12H20NOþ, calc. 194.1545).
(2R)-3-Phenyl-2-[(2-propylphenyl)amino]propan-1-ol (7). Yellow oil, 31% yield. [a]2D5 ¼ þ87.26
1
(c ¼ 0.5, CHCl3). IR (CCl4): 3488, 2814, 2359, 1588, 1510, 1257, 1011. H-NMR: 0.94 (t, J ¼ 7.4, 3 H);
1.48 – 1.58 (m, 2 H); 2.36 (t, J ¼ 7.8, 2 H); 2.89 (dd, J ¼ 13.7, 7.2, 1 H); 2.95 (dd, J ¼ 13.7, 5.7, 1 H); 3.55 (dd,
J ¼ 10.7, 4.7, 1 H); 3.71 (dd, J ¼ 10.8, 4.3, 1 H); 3.76 – 3.80 (m, 1 H); 6.69 (dt, J ¼ 7.5, 1.1, 1 H); 6.74 (d, J ¼
8.2, 1 H); 7.02 (dd, J ¼ 7.4, 1.5, 1 H); 7.09 – 7.13 (m, 1 H); 7.18 – 7.21 (m, 3 H); 7.25 – 7.29 (m, 2 H).
13C-NMR: 144.6; 138.1; 129.2; 129.0; 128.5; 127.4; 126.5; 117.6; 111.2; 63.2; 55.6; 37.5; 33.3; 21.7; 14.3. HR-
CI-MS: 270.1857 ([M þ H]þ, C18H24NOþ; calc. 270.1858).
2-[(2-Propylphenyl)amino]phenol (8). The procedure above was applied, at the end of reaction,
15 ml 1% HCl was added. The aq. phase was washed with Et2O, the org. phase concentrated and the
resulting oil purified by SiO2 chromatography. Yellow oil, 12% yield. IR (CCl4): 3426, 2964, 2933, 2873,
2352, 1698, 1584, 1495, 1455, 1240, 912. 1H-NMR: 0.94 (t, J ¼ 7.32, 3 H); 1.64 (sext, J ¼ 7.48, 2 H); 2.54 (t,
J ¼ 7.64, 2 H); 5.15 (br. s, 1 H); 5.60 (br. s, 1 H); 6.62 (d, J ¼ 7.82, 1 H); 6.78 – 6.81 (m, 2 H); 6.88 (d, J ¼
7.00, 1 H); 6.95 – 6.99 (m, 3 H); 7.08 (d, J ¼ 7.35, 1 H). 13C-NMR: 150.4; 142.8; 130.1; 129.9; 129.8; 127.0;
125.3; 123.8; 121.1; 120.8; 116.1; 115.3; 33.4; 22.5; 14.2. HR-CI-MS: 228.1386 ([M þ H]þ, C15H18NOþ;
calc. 228.1388).

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Helvetica Chimica Acta – Vol. 91 (2008)
2-(2-Propylphenoxy)ethanol (9): Yellow oil, 45% yield. IR (CCl4): 3426, 2961, 2934, 2873, 2352, 2250,
1
1698, 1588, 1493, 1452, 1378, 1291, 1241, 1129, 1047, 908. H-NMR: 0.86 (t, J ¼ 7.4, 3 H); 1.48 – 1.59 (m,
2 H); 2.52 (t, J ¼ 7.6, 2 H); 3.84 – 3.87 (m, 2 H); 3.95 – 3.98 (m, 2 H); 6.74 (d, J ¼ 6.7, 1 H); 6.81 (t, J ¼ 7.4,
1 H); 7.03 – 7.08 (m, 2 H). 13C-NMR: 156.5; 131.3; 130.1; 126.9; 120.9; 111.6; 69.4; 61.7; 32.2; 23.1; 14.1.
HR-CI-MS: 181.1220 ([M þ H]þ, C11H17Oþ2 ; calc. 181.1229).
Synthesis of 1-Ethoxy-2-propylbenzene (10) [13]. 1a (1.00 g, 4.61 mmol) was mixed with 1.3 equiv. of
triethyl orthoformate (0.9 g, 6.0 mmol) in 0.5 ml EtOH. Later, 0.05 ml AcCl was added to the mixture,
stirred overnight, filtered through a pad of SiO2 with 20 :1 hexane/AcOEt, and concentrated to give ca.
0.8 g of a crude oil. To the resulting oil, 1.0 equiv. of tBuOK (0.77 g, 6.88 mmol) in 5 ml dry DMSO was
added, the mixture was immersed in an oil bath at 808 and agitated for 3 h with a magnetic stirrer, and
purified by FC without workup to yield 11 (0.23 g, 30% yield).
Synthesis of 2-(2-bromoprop-2-en-1-yl)-4-methylcyclohexanone (1c). 1-(4-Methylcyclohex-1-enyl)-
pyrrolidine [14] (7.8 g, 0.047 mol) was mixed with 2 equiv. of 2,3-dibromopropene (18.9 g, 0.095 mol) in
30 ml dry dioxane at 08 under Ar and refluxed for 3 h. Later, 15 ml 1% HCl soln. was added, and the
mixture was refluxed for another 3 h. The mixture was concentrated in vacuo, the aq. phase washed with
Et2O. The Et2O phase was washed with sat. brine, dried over MgSO4, and concentrated. The resulting oil
was purified by vacuum distillation: B.p. 1018 (3 Torr): (4.54 g, 42% yield). IR (CCl4) 1714, 1631, 1133,
890. 1H-NMR: 0.92 – 2.94 (m, 13 H); 5.36 (br. s, 1 H); 5.53 (br. s, 1 H). HR-CI-MS: 231.0377 ([M þ H]þ,
C10H16BrOþ; calc. 231.0385).
2-(4-Methyl-2-propylphenoxy)ethanol (11). Yellow oil, 34% yield. IR (CCl4): 3360, 2960, 2873, 2444,
1715, 1613, 1502, 1457, 1252, 1230, 1079, 1042, 978, 936, 909. 1H-NMR: 0.88 (t, J ¼ 7.4, 3 H); 1.60 – 1.67 (m,
2 H); 2.26 (s, 3 H); 2.50 (t, J ¼ 7.4, 2 H); 3.92 – 3.95 (m, 2 H); 4.03 – 4.05 (m, 2 H); 6.73 (d, J ¼ 8.1, 1 H);
6.93 – 6.95 (m, 2 H). 13C-NMR: 153.3; 130.1; 129.9; 129.1; 126.1; 110.7; 68.6; 60.8; 31.2; 22.2; 19.5; 13.1.
HR-CI-MS: 195.1377 ([M þ H]þ, C12H19O2þ ; 195.1385).
(2R)-2-[(4-Methyl-2-propylphenyl)amino]butan-1-ol (12). Yellow oil, 37% yield. [a]2D5 ¼ ꢀ3.71 (c ¼
1.2, CHCl3). IR (CCl4): 3426, 2965, 2932, 2874, 2352, 1698, 1512, 1456, 1261, 1059. 1H-NMR: 0.91 (t, J ¼
7.5, 3 H); 0.95 (t, J ¼ 7.4, 3 H); 1.50 – 1.67 (m, 5 H); 2.18 (s, 3 H); 2.37 – 2.41 (m, 2 H); 3.36 – 3.42 (m,
1 H); 3.50 (dd, J ¼ 10.8, 5.9, 1 H); 3.72 (dd, J ¼ 10.7, 4.1, 1 H); 6.58 (d, J ¼ 8.1, 1 H); 6.83 – 6.87 (m, 2 H).
13C-NMR: 141.8; 129.3; 126.4; 126.0; 125.6; 110.7; 63.1; 55.9; 32.4; 24.1; 21.1; 19.4; 13.3; 9.6. HR-CI-MS:
222.1874 ([M þ H]þ, C14H24NOþ; calc. 222.1858).
(6E)-1-Ethoxy-4,4-dimethyl-6-(prop-2-en-1-ylidene)cyclohexene (15). 4,4-Dimethylcyclohexanone
(10.0 g, 0.079 mol) was dissolved in 150 ml of dry THF and brought to ꢀ 788 under Ar atmosphere. At
this temp., 1.1 equiv. LDAsoln. (87 ml, 2 m in THF/heptane/ethylbenzene) was added dropwise within
0.5 h via mixing and mixed for another h at this temp. Later, 1.1 equiv. of propargyl bromide (9.36 ml,
80% soln. in toluene) was added dropwise at ꢀ 788 in 0.5 h and mixed for another h. The reaction was
quenched by addition of 50 ml aq. NH4Cl, 100 ml of Et2O was added, and the org. phase separated. The
aq. phase was washed with 100 ml of Et2O, the org. phases were combined, washed with brine, dried over
MgSO4, and concentrated in vacuo. The remaining oil was distilled under vacuum: B.p. 81 – 1108 (3 Torr),
yield 4.92 g of 4,4-dimethyl-2-(prop-2-yn-1-yl)cyclohexanone (13) as a yellow oil (38% yield, 0.030 mol)
of practical purity. Later, 13 was protected in the same way as 10 to get the corresponding acetal, and an
oil was obtained. This oil was purified by chromatography from chromatography grade basic alumina
(Fluka) using AcOEt/hexanes as eluent to yield 2.87 g of 1-ethoxy-4,4-dimethyl-6-(prop-2-yn-1-
1
yl)cyclohexene 14 as a colorless oil (47% yield, 0.014 mol). H-NMR: 0.92 (s, 3 H); 0.97 (s, 3 H); 1.26
(t, J ¼ 6.91, 3 H); 1.34 – 2.63 (m, 8 H); 3.59 – 3.74 (m, 2 H); 4.54 (d, J ¼ 5.73, 1 H). 13C-NMR: 153.8; 93.8;
83.3; 69.0; 61.9; 42.2; 37.9; 34.7; 31.4; 29.8; 25.0; 22.7; 14.0.
When the general procedure for aromatization was applied to 14, 244 mg of 15 was obtained by
chromatography over SiO2 (9% yield, 1.27 mmol). 1H-NMR: 0.95 (s, 6 H); 1.35 (t, J ¼ 6.94, 3 H); 2.03 (d,
J ¼ 4.35, 2 H); 2.27 (s, 2 H); 3.77 (q, J ¼ 6.91, 2 H); 4.83 (t, J ¼ 4.35, 1 H); 5.13 (d, J ¼ 9.86, 1 H); 5.30 (d,
J ¼ 16.36, 1 H); 6.56 – 6.72 (m, 2 H). 13C-NMR: 151.4; 132.7; 123.2; 117.6; 99.2; 62.6; 39.6; 38.5; 30.5; 29.7;
28.3; 14.8. HR-CI-MS: 193.1586 ([M þ H]þ, C13H21Oþ; calc. 193.1592).

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Received February 28, 2008