Synthesis of 8-methylnonane-1,6,7-trien-4-one and related allenes as potentially useful synthetic precursors

Article abstract of DOI:10.4314/bcse.v26i1.11

The allenic ketone 8-methylnonane-1,6,7-trien-4-one and related allenes have been synthesized from simple commercially available materials. Since allenes analogous to 8-methylnonane-1,6,7-trien-4-one have previously been transformed to substituted bicyclo[3.3.0]octanones via corresponding bicyclo[3.2.0]heptanones, it is anticipated that the present allenic ketone may also undergo similar transformations. Substituted bicyclo[3.3.0]octanones are known synthetic precursors of tricyclic sesquiterpenes. Thus, 8-methylnonane-1,6,7- trien-4-one presents itself as a possible precursor for the synthesis of tricyclopentanoid ring system present in sesquiterpenes such as hirsutene and Δ⁹⁽¹²⁾-capnellene.

Full text of DOI:10.4314/bcse.v26i1.11

Bull. Chem. Soc. Ethiop. 2012, 26(1), 103-113.
Printed in Ethiopia
DOI: http://dx.doi.org/10.4314/bcse.v26i1.11
ISSN 1011-3924
 2012 Chemical Society of Ethiopia
SYNTHESIS OF 8-METHYLNONANE-1,6,7-TRIEN-4-ONE AND RELATED ALLENES
AS POTENTIALLY USEFUL SYNTHETIC PRECURSORS
S.J.M. Mdachi*
Department of Chemistry, University of Dar es Salaam P.O. Box 35061, Dar es Salaam,
Tanzania
(Received February 7, 2011; revised September 20, 2011)
ABSTRACT. The allenic ketone 8-methylnonane-1,6,7-trien-4-one and related allenes have been synthesized
from simple commercially available materials. Since allenes analogous to 8-methylnonane-1,6,7-trien-4-one have
previously been transformed to substituted bicyclo[3.3.0]octanones via corresponding bicyclo[3.2.0]heptanones,
it is anticipated that the present allenic ketone may also undergo similar transformations. Substituted
bicyclo[3.3.0]octanones are known synthetic precursors of tricyclic sesquiterpenes. Thus, 8-methylnonane-1,6,7-
trien-4-one presents itself as a possible precursor for the synthesis of tricyclopentanoid ring system present in
sesquiterpenes such as hirsutene and ∆9(12)-capnellene.
KEY WORDS: 8-Methylnonane-1,6,7-trien-4-one, Allenic ketone, Allenes, Ene-allenes
INTRODUCTION
Allenes comprise a class of compounds characterized by two cumulated double bonds [1]. One
of the first synthesized allene is penta-2,3-dienedioic acid (1) (Figure 1). It was reported as early
as in 1887 by Burton and Pechmann [2], but the structure was not confirmed until 1954 [3]. The
unjustified belief that allenes would be unstable because of the cumulated system greatly
hindered the development of allene chemistry. For this reason and the lack of methodology for
their preparation in the first half of the 20th century, allenes were for a long time viewed as
laboratory curiosities. Nowadays, the preparation of allenic hydrocarbons and variously
functionalized allenes has been widely investigated and a good number of methods exist for
obtaining a variety of allenes [4]. The unusual chemistry and applications of allenes as synthetic
intermediates have also been extensively investigated and reviewed [5-8]. Of particular interest
to us is the application of intramolecular [2+2] cycloaddition of ene-allenes [9, 10] so as to
assemble a functionalized bicyclo[3.3.0]octanone via a corresponding bicyclo[3.2.0]heptanone.
We envisioned assembling an appropriately substituted bicyclo[3.3.0]octanone, which is
capable of being transformed to the tricyclic sesquiterpene hirsutene (2) and/or ∆9 (12)-capnellene
(3) (Figure 1).
H
O
O
H
H
HO
OH
H
H
H
Penta-2,3-dienedioic acid (1)
Hirsutene (2)
∆
9 (12)-Capnellene (3)
9(12)
Figure 1. Penta-2,3-dienedioic acid (1), tricyclic sesquiterpene hirsutene (2) and
capnellene (3).
∆
-
Retrosynthetic analyses of compounds 2 and 3 based on the aforementioned proposal should
lead to 8-methylnonane-1,6,7-trien-4-one (4a) and 2,8-dimethylnonane-1,6,7-trien-4-one (4b) as
depicted in Scheme 1.
__________
*Corresponding author. E-mail: stephenmdachi@yahoo.com

104
S.J.M. Mdachi
H
O
H
H
H
H
O
H
H
Hirsutene (2)
bicyclo[3.3.0]octanone 5a bicyclo[3.2.0]heptanone (6a)
H
H
H
H
O
O
H
9 (12)-Capnellene (3)
bicyclo[3.3.0]octanone 5b bicyclo[3.2.0]heptanone (6b)
∆
6a / 6b
O
R
4a, R = H
4b, R = CH3
Scheme 1
It was anticipated that the [2+2] ene-allene cycloaddition of compound 4 should lead to the
bicyclo[3.2.0]heptanone 6 and the acid catalysed rearrangement of 6 should furnish the
bicyclo[3.3.0]octanone 5. The difference in the position of the gem-dimethyl substructure in
compounds 5a and 5b can be mechanistically rationalized by the anticipated acid catalysed
rearrangement of compound(s) 6 as depicted in Scheme 2.
a
HBr/AcOH
O
b
O
R
6a, R = H
6b, R = CH3
R
7
a
b
O
O
R
8
R
9
- H
Br
Br
- H
Br
Br
O
O
O
O
R
R
R
R
10
11
12
13
5b
5a
Scheme 2
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Synthesis of 8-methylnonane-1,6,7-trien-4-one and related allenes as synthetic precursors 105
Protonation of 6 should lead to the carbocation 7, that can rearrange to 8 (path a) or to 9
(path b). Reactions with bromide ion or deprotonation of 8 and 9 should give compounds 10-13.
Debromination of 10 and hydrogenation of 11 should afford the desired bicyclo[3.3.0]octanone
5b. Similarly, debromination of 12 and hydrogenation of 13 should lead to 5a.
Precedence of the acid catalysed rearrangement was available from the previous observation
[11] that the treatment of compound 14 with HBr led to a practically quantitative conversion to
15 (Scheme 3).
Br
H
H
HBr-AcOH
50 - 60 0C
O
O
15
14
Scheme 3
In order to test our retrosynthesis (Scheme 1), our first task was to synthesize the allenic
ketones 4a and 4b. The present paper, therefore, focuses attention on synthetic work with 8-
methylnonane-1,6,7-trien-4-one (4a) as the target.
RESULTS AND DISCUSSION
Initially we designed a synthetic strategy that aimed at 5-methyl-3,4-hexadienal (16) as a key
intermediate towards the targeted allenic ketones 4a and 4b. One obvious way to obtain
compound 16 would be to oxidize its alcohol precursor, that is 5-methyl-3,4-hexadienol (17).
Attempts were made to prepare the dienol 17 by first employing a Claisen type [3,3] sigmatropic
rearrangement of the propargyl vinyl ether 18, which was generated in situ from 2-methyl-3-
butyn-2-ol, triethyl orthoacetate and propionic acid (Scheme 4), to give ethyl 5-methyl-3,4-
hexadienoate (19). On encountering a problem in the reduction of the β-allenic ester 19 to
obtain the alcohol 16, a new route to the latter compound was conceived. In this case, 2-(2,2-
dibromo-3,3-dimethylcyclopropyl) ethanol (20) was envisioned as the immediate precursor to
the allenic alcohol 17. Compound 20 was obtained in 84-87% yield from 21 through a Baeyer-
Villiger oxidation followed by a base catalysed hydrolysis of the resulting ester 22. The ketone
21 was prepared in 90% overall yield from the readily available 6-methyl-5-hepten-2-one in
three simple steps, which are: protection of the carbonyl group as a cyclic ketal [12], addition of
the dibromo carbene and deprotection of carbonyl group in that order. Therefore, the overall
yield of alcohol 20 from 6-methyl-5-hepten-2-one was 76%.
Having obtained compound 20 in good yield, the stage was set for the preparation of 5-
methyl-3,4-hexadienol (17), the immediate precursor for 16. The conversion of 20 to 17 was
achieved in 95% yield by treatment of an ice-cooled ethereal solution of compound 20 with an
ethereal solution of 1.5 M MeLi in an inert atmosphere. It is worth mentioning that 5-methyl-
3,4-hexadienol (17) was prepared in 76% overall yield following a six steps procedure from 1,3-
propanediol [10]. The preparation reported in the present work afforded the dienol 17 in
comparable yields (72%) in six steps utilizing simple reagents. However, oxidation of the
allenic alcohol 17 by the chromium trioxide-pyridine complex gave the isomerized aldehyde 5-
methyl-2,4-hexadienal (23) instead of the targeted aldehyde 16.
Bull. Chem. Soc. Ethiop. 2012, 26(1)

106
S.J.M. Mdachi
O
O
i
OAc
3 steps
Br Br
Br Br
22
21
ii
iv
O
OH
iii
OH
EtO
19
17
Br Br
20
v
O
O
EtO
18
16
O
EtO
O
CH2
EtO H
23
EtCO2H
+
CH3C(OEt)3
OH
(i) CF3CO3H, CH2Cl2, Na2HPO4 (ii) OH-, H2O (iii) MeLi, Ether (iv) LiAlH4 (v) CrO3.2Pyr.
Scheme 4
The 2,4-hexadienal 23 was characterized on the basis of spectroscopic data. The appearance
of the carbonyl group absorption at 1680 cm-1 in the IR spectrum is characteristic of α,β-
unsaturated aldehydes. The H NMR spectrum indicated the presence of three olefinic protons
1
(contrary to one olefinic proton as it would be for compound 16), a multiplet at 6.0 ppm due to
the αH and the γH, and a dublet dublets at 7.5 ppm due to the βH. The appearance of a dublet
for the adehydic proton at 9.5 ppm suggests the presence of one proton at the α-carbon (contrary
to two protons as it would be the case of the allenic aldehyde 16). The singlet at 1.9 ppm is due
to the gem-dimethyl protons. The UV spectrum showed an absorption maximum at 274.5 nm (ε
= 17600) which is expected for a dienal chromophore.
Dissatisfied with this isomerization of the anticipated aldehyde 16 to 23, we terminated
efforts to prepare 16 as a key intermediate towards the targeted allenic ketones 4a and 4b. Our
second route towards the allenic ketone 4a is summarized in Scheme 5. In this strategy we
aimed at the 1,3-dthiane derivative 24, which we anticipated would easily be converted to 4a. 2-
Allyl-1,3-diathiane (25) was obtained in 90% yield from the lithium derivative of 1,3-dithiane
(26) and allyl bromide. However, the conversion of 25 to 27 proved to be problematic,
presumably because the intermediate, lithiated 25, could have reacted with the acetylenic proton
of the propargylic bromide and thereby regenerating 25. To circumvent this problem, we
decided to form the allene functionality prior to coupling with 25. We, thus, prepared the allenic
Bull. Chem. Soc. Ethiop. 2012, 26(1)

Synthesis of 8-methylnonane-1,6,7-trien-4-one and related allenes as synthetic precursors 107
bromopentadiene 29, albeit in very low yield, starting from the commercially available
propargyl alcohol. The diol 28 was prepared by reacting acetone and the ethynyl Grignard
reagent derived from propargyl alcohol. Treatment of 28 with HCl/CaCl2 afforded 4-chloro-4-
methyl-2-pentyn-1-ol, which was converted, without isolation, to 4-methyl-2,3-pentadien-1-ol
by reaction with LiAlH4. Treatment of the latter allenic pentadienol with PBr3 furnished the
allenic bromopentadiene 29, which was coupled with 25 to furnish 24 in 58% yield. The allene
24 was characterized on the on the basis of spectral data. The presence of the allenic bond is
shown by an infrared band at 1955 cm-1. The 1H NMR spectrum is consistent with the structure.
However the low yield of 29 coupled with the moderate yield of 24 left us with insufficient
material for subsequent transformations. This was certainly not satisfactory, and we looked for
alternative ways of synthesizing compound 4a.
H
S
S
S
S
i
ii
S
S
25
26
27
v
OH
iii
S
S
OH
Br
24
OH
28
iv
O
29
4a
(i) (a) BuLi (b) allyl bromide (ii) (a) BuLi (b) propargyl bromide
(iii) (a) EtMgBr (b)acetone (iv) (a) HCl/CaCl2 (b) LAH (c) PBr3
(v) (a) BuLi (b) 29
Scheme 5
The fact that 2-(2,2-dibromo-3,3-dimethylcyclopropyl) ethanol (20) was obtained in 76%
overall yield from 6-methyl-5-hepten-2-one prompted us to revisit our first strategy (Scheme 4,
vide supra) with some modifications in mind. Thus, in our third strategy, we planned to form
the aldehyde functionality prior to the introduction of the allenic moiety. This strategy aimed at
circumventing the isomerization that occurred for the allenic aldehyde 16. This route towards
the allenic ketone 4a is depicted in Scheme 6 [steps (i)–(iii) are included for completeness as
they have already been discussed in Scheme 4].
Swern [13] oxidation of alcohol 20 furnished 2-(2,2-dibromo-3,3-dimethylcyclopropyl)
ethanal (30), which was transformed, without isolation, to 1-(2,2-dibromo-3,3-
dimethylcyclopropyl)-4-penten-2-ol (31) in 71% overall yield from 20. Treatment of 31 with N-
O-bis-trimethylsilylacetamide in the presence of a catalytic amount of trimethylchlorosilane [14]
gave the silyl ether 32 in 90% yield. The silyl ether was converted to the vinyl allene 33 (61%
yield) by treatment of 32 with MeLi at -5 °C, and Jones oxidation of the allene gave the desired
ketone 4a in 61% yield. Infrared absorption at 1965 and 1705 cm-1 are characteristic of the
allenic linkage and isolated carbonyl group, respectively, and the NMR spectra fully confirm the
structure of the desired allenic ketone 4a.
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108
S.J.M. Mdachi
O
O
i
OAc
ii
iii
Br Br
22
Br Br
21
iv
O
OH
vi
v
OH
Br Br
Br Br
Br Br
31
20
30
vii
viii
OSiMe3
O
OSiMe3
Br Br
32
33
4a
(i) (a) HOCH2CH2OH/H+ (b) CBr2 (c) H3O+ (ii) CF3CO3H (iii) 15% NaOH
(iv) DMSO-(COCl)2 (v) allylzinc bromide (vi) N-O-bis-trimethylsilylacetamide
(vii) MeLi (viii) CrO3 (Jones)
Scheme 6
Although we are not fully satisfied with the length (large number of steps) and linearity of
the strategy, we nevertheless have successfully prepared the desired ketone 4a in 21% overall
yield from compound 21. It is, therefore, possible to prepare sufficient amounts of compound 4a
by scaling up the synthesis or conducting repeated preparations. We also have prepared the
thioketal-protected target ketone in the form of compound 24 (Scheme 5). It is, therefore,
worthy revisiting this shorter and convergent route towards 4a with the purpose to improve the
yield of the bromopentadiene 29 and, subsequently, that of compound 24. Furthermore, it may
be desirable to design a shorter and convergent route to 8-Methylnonane-1,6,7-trien-5-one, a
regioisomer of 4a, using some of the compounds prepared in this work, for example, 4-methyl-
2,3-pentadien-1-ol, which was the precursor for the bromopentadiene 29 in Scheme 5.
EXPERIMENTAL
General
Reagents. Unless otherwise indicated all analytical grade reagents were used without further
purification. Other grades were purified according to known procedures before use.
Instruments. Capillary gas-liquid chromatography (GLC) analyses were carried out on a Varian
3400 Gas Chromatograph using a supelcowax 10 wall-coated column of 30 m length and 0.25
mm internal diameter. Other analytical GLC were carried out on either a Hewlett Packard 5710a
Gas Chromatograph using 3% SP 2100 packed column of 2.5 m length and 2 mm internal
diameter or on Chrompack CP 9001 Gas Chromatograph using 3% OV-17 packed column of 2
”
m x ¼ x 2 mm dimensions. Thin-layer chromatography (TLC) was carried out on aluminium
plates pre-coated with silica gel 60 F254. The spots were visualized by illuminating with UV
lump (254 nm) or by using p-anisaldehyde spray reagent. Infrared (IR) spectra were recorded on
either a Perkin-Elmer Infrared Spectrometer 1310 or a Magna-IR Spectrometer 550.
Absorptions are indicated as (s) = strong, (m) = medium, and (w) = weak. NMR Spectra: 1H and
13C NMR spectra were recorded on the following instruments: Jeol PMX60SI NMR
Spectrometer operating at 60 MHz, Varian Gemini-200 NMR spectrometer, varian XL-300
NMR Spectrometer, and dpx-300 NMR Spectrometer. Tetramethylsilane (TMS) was used as an
Bull. Chem. Soc. Ethiop. 2012, 26(1)

Synthesis of 8-methylnonane-1,6,7-trien-4-one and related allenes as synthetic precursors 109
internal standard. Ultraviolet (UV) spectra were recorded on a Shimadzu UV-VIS Recording
Spectrophotometer UV-260. Melting points were taken on a Buchi melting point apparatus and
are uncorrected.
1,3-Dithiane (26) was prepared from 1,3-propanethiol and formaldehyde dimethylacetal in the
presence of catalytic amount of BF3.OEt2 according to literature, m.p. 51.5-52.5 °C, (lit. [15]
m.p. 53-54 °C). 1H NMR (200 MHz, CDCl3): δ 2.10 (m, 2 H), 2.85 (t, J 6.6 Hz, 4 H), 3.78 (s, 2
H).
2-Allyl-1,3-dithiane (25). A solution of 1,3-dithiane (6 g, 0.05 mol) in THF (150 mL) was
cooled to -40 °C and kept under a N2 atmosphere. To the dithiane-THF solution was dropwise
added n-BuLi (33 mL, 0.0525 mol). The resulting solution was stirred at -25 to -15 °C for 4 h
and the cooled to -75 °C followed by addition of allyl bromide (6.05 g, 0.05 mol). The resulting
mixture was stirred overnight when the temperature gradually rose from -75 °C to 0 °C. The
reaction was quenched by addition of 50 mL of water. The aqueous phase was extracted with (5
x 30 mL) and the combined organic solution dried (K2CO3-MgSO4). Evaporation of the solvent
left an oil which was distilled under reduced pressure to give 7.215 g (90%) of 25 [16], b.p.
102-104 °C/10 mmHg. IR (film): 3066 (m), 2892 (s), 1642 (m), 1414 (s), 991 (s), 910 (s), 769
1
(s) cm-1. H NMR (200 MHz, CDCl3): δ 1.85 (m, 1 Η), 2.10 (m, 1 Η), 2.50 (t, J 6.6 Hz, 2 H),
2.85 (m, 4 H), 4.10 (t, J 6.6 Hz, 1 H), 5.10 (m, 2 H), 5.85 (m, 1 H).
4-Methyl-2-pentyn-1,4-diol (28). To ethylmagnesium bromide, prepared in the usual way from
ethyl bromide (87.18 g, 0.8 mol) and magnesium (19.44 g, 0.8 mol) in ether (600 mL) and
cooled to 0 °C, was added a solution of the propargyl alcohol (22 g, 0.39 mol) in THF (100
mL). The resulting mixture was stirred at room temperature for 3 h and then a solution of
acetone (23 g, 0.4 mol) in THF (100 mL) was added. Stirring at room temperature was
continued overnight and then the reaction was quenched with saturated aqueous NH4Cl
solution. The organic phase was separated and the aqueous phase was subjected to continuous
extraction with ether. The combined organic solution was dried (MgSO4). After evaporation of
the solvent a viscous oil was left. Distillation under reduced pressure gave 32.20 g (72%) of the
diol 28, b.p. 80 °C/0.05 mmHg, (lit. [17] b.p. 91 °C/1 mmHg). IR (film): 3300 (s), 2960 (s),
1350 (s), 1225 (s), 1150 (s), 1050 (s), cm-1. 1H NMR (200 MHz, CDCl3):
δ 1.50 (s, 6 Η), 4.05 (s, 2 H), 4.27 (s, 2 H). 13C NMR (50 MHz, CDCl3): δ 32.62 (2 CH3), 51.74
(C-O), 66.08 (C-O), 81.17 (acetylenic C), 91.03 (acetylenic C).
4-Chloro-4-methyl-2-pentyn-1-ol. To a mixture of 37% HCl (16 mL, 0.177 mol) and CaCl2 (16
g, 0.144 mol) the diol 28 (12 g, 0.104 mol) was added and the resulting mixture was shaken
with cooling (ice-water bath) for 5 min. The two layers were separated and the aqueous layer
was extracted several times with ether. The combined organic solution was dried (K2CO3-
MgSO4). Filtration followed by evaporation of the solvent gave the crude 4-chloro-4-methyl-2-
pentyn-1-ol [18] as a dark brown oil. A small quantity was purified by flash chromatography
(silica, 1:2 EtOAc/pet. ether) to give a pure sample of the chloropentynol for spectroscopic
analyses. IR (film): 3300 (s), 2920 (s), 1610 (m), 1430 (s), 1360 (s), 900 (s), cm-1. 1H NMR (200
MHz, CDCl3): δ 1.81 (s, 6 Η), 2.60 (s, 1 H), 4.30 (s, 2 H). 13C NMR (50 MHz, CDCl3): δ 36.04
(2 CH3), 52.00 (C-O), 58.75 (C-Cl), 83.00 (acetylenic C), 89.00 (acetylenic C).
4-Methyl-2,3-pentadien-1-ol. The crude 4-chloro-4-methyl-2-pentyn-1-ol was dissolved in dry
ether (50 mL) and added dropwise to a suspension of LiAlH4 (5.6 g, 0.15 mol) [19] in ether
(200 mL) kept at room temperature. After complete addition of the chlorohydrin-ether solution,
the mixture was refluxed for 45 min, cooled and water added dropwise to quench the reaction.
Bull. Chem. Soc. Ethiop. 2012, 26(1)

110
S.J.M. Mdachi
The reaction mixture was worked up as usual and the product purified by flash chromatography
(silca, 1:2 Et2O/pentane) to give 4.945 g, (53%) of 4-methyl-2,3-pentadien-1-ol [20]. IR (film):
1
3300 (s), 2900 (s), 1955 (m), 1430 (s), 1400 (s), 1000 (s), cm-1. H NMR (200 MHz, CDCl3):
δ 1.70 (d, J 1 Hz, 3 Η), 1.71 (d, J 1 Hz, 3 Η), 2.19 (s, 1 H), 4.04 (d, J 4.8 Hz, 2 Η), 5.15 (m, 1
H).
1-Bromo-4-methylpenta-2,3-diene (29). To a cooled mixture of 4-methyl-2,3-pentadien-1-ol
(3.3 g, 0.034 mol) in pet. ether (15 mL) and pyridine (3.4 mL) was dropwise added a solution of
PBr3 (5.1 g, 0.018 mol) in pet. ether (12 mL). The reaction progress was monitored by GLC and
found to be complete within 30 min since complete addition of PBr3. The mixture was poured
into ice water and the organic phase separated from the aqueous phase. The aqueous phase was
extracted with ether and the combined organic solution was dried (MgSO4). Filtration and
removal of the solvent left the crude product as a liquid. Distillation under reduced pressure
gave only 1.1 g (20%) of the bromopentadiene 29, bp. 40 °C/10 mmHg. A substantial degree of
polymerization occurred. 1H NMR (200 MHz, CDCl3): δ 1.70 (s, 3 Η), 1.71 (s, 3 Η), 3.90 (d, J 9
Hz, 2 H), 5.25 (m, 1 H).
2-Allyl-2-(4-methyl-2,3-pentadienyl)-1,3-dithiane (24). To a solution of 2-allyl-1,3-dithiane (25)
(0.8 g, 5 mmol) in dry THF (15 mL), cooled to -40 °C and kept under a N2 atmosphere, was
dropwise added n-BuLi (5.25 mmol) [16]. The resulting mixture was stirred for 3 h at -25 to -15
°C and then cooled to -75 °C followed by addition of the bromopentadiene 29 (0.8 g, 5 mmol).
The resulting mixture was stirred overnight when the temperature rose from -75 to 0 °C. The
usual workup followed by flash chromatography (silica, pet. ether/EtOAc 9:1) gave 0.7 g (58%)
1
of 24 as a viscous oil. IR (film): 2895 (s), 1955 (m), 1625 (m), 1420 (s), 985 (s), 910 cm-1. H
NMR (200 MHz, CDCl3): δ 1.68 (s, 3 Η), 1.69 (s, 3 Η), 1.95 (m, 2 H), 2.58 (d, J 9 Hz, 2 Η),
2.65 (d, J 9 Hz, 2 Η), 2.86 (m, 4 H), 5.00 (m, 1 H), 5.10 (m, 2 H), 5.85 (m, 1 H).
1-Acetoxy-2-(2,2-dibromo-3,3-dimethylcyclopropyl)ethane (22) was prepared in 95% yield by
oxidation of 4-(2,2-dibromo-3,3-dimethylcyclopropyl)butan-2-one with peroxytrifluoroacetic
1
acid [21]. IR (film): 2900 (s), 2800 (s), 1739 (s), 1455 (s), 1360 (s), 1230 (s) cm-1. H NMR
(200 MHz, CDCl3): δ 1.18 (s, 3 H), 1.28 (t, J 6.6 Hz, 1 H), 1.37 (s, 3 H), 1.75 (m, 2 H), 2.05 (s,
3 H), 4.17 (t, J 6.6 Hz, 2 H).
2-(2,2-dibromo-3,3-dimethylcyclopropyl)ethanol (20) [22] was obtained in 92% yield by base
1
catalyzed hydrolysis of the acetate 22. H NMR (200 MHz, CDCl3): δ 1.20 (s, 3 Η), 1.26 (t, J
6.6 Hz, 1 H), 1.30 (s, 3 H), 1.70 (m, 2 H), 2.10 (br s, 1 H), 3.75 (t, J 6.6 Hz, 2 H).
5-Methyl-3,4-hexadien-1-ol (17). A 250 mL two necked flask provided with a condenser and a
septum, kept under N2 stream, was charged with a solution of alcohol 20 (13.6 g, 50 mmol) in
dry ether (100 mL) and cooled in an ice-water bath. An ethereal solution of 1.5 M MeLi (83 mL,
125 mmol) was added dropwise with stirring. The reaction mixture was further stirred for 15
min and then poured into cold saturated NH4Cl solution. The ether layer was separated and the
aqueous layer extracted with ether. The combined ethereal solution was dried (Na2SO4) and the
solvent distilled of yielding a liquid (5.3 g, 95%) which was pure enough for spectroscopic
characterization. B.p. 74-76 °C/20 mmHg (lit. [23] 75 °C/20 mmHg). IR (film): selected bands
1
at 3320 (s) OH, 2900 (s) aliphatic CH, 1960 (w) allenic C=C=C str., cm-1. H NMR (200 MHz,
CDCl3): δ 1.70 (d, 6 H), 2.20 (q, 2 H), 2.40 (broad s, 1 H), 3.70 (t, 2 H), 5.0 (m, 1 H).
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Synthesis of 8-methylnonane-1,6,7-trien-4-one and related allenes as synthetic precursors 111
5-Methyl-2,4-hexadienal (23). Chromium trioxide (4 g, 40 mmol) was added portion-wise to a
stirred solution of dry pyridine (6.3 g, 80 mmol) in CH2Cl2 (75 mL) at room temperature (with
occasional cooling in a cold water bath). After the addition of CrO3 was complete, the mixture
was further stirred for 15 min and then the allenic alcohol 17 (0.56 g, 5 mmol) in dry CH2Cl2
(2.5 mL) was added dropwise with stirring. The mixture was stirred for 30 min and then the
CH2Cl2 solution was decanted from the black-tarry solid, the solid was washed several times
with ether, the organic solutions combined and washed thrice with 10% aqueous NaOH, once
with 5% aqueous HCl, 5% aqueous NaHCO3 and saturated aqueous NaCl solution. After drying
(MgSO4) and removal of the solvents, GLC analysis of the residue indicated presence of
substantial amount of pyridine, which was removed by column chromatography on silica gel
(CH2Cl2) yielding 23 as a yellow oil (0.36 g, 65%). IR (film): selected bands at 3310 (w), 2900
1
(s) aliphatic CH, 1680 (s) α,β-unsaturated C=O, cm-1. H NMR (200 MHz, CDCl3): δ 1.90 (s, 6
H), 6.00 (m, 2 H, αH + γH), 7.50 (dd, 1 H, βH), 9.50 (d, 1 H, CH=O). UV (hexane): λmax 274.5
nm (ε = 17600).
Ethyl 5-methyl-3,4-hexadienoate (19). The β-allenic ester was prepared according to literature
[24]. IR (film): selected bands at 2920 (s) aliphatic CH, 1970 (w) allenic C=C=C str., 1735 (s)
1
C=O ester, cm-1. H NMR (200 MHz, CDCl3): δ 1.25 (t, 3 H), 1.70 (d, 6 H), 3.0 (d, 2 H), 4.10
(q, 2 H), 5.05 (m, 1 H).
1-(2,2-dibromo-3,3-dimethylcyclopropyl)-4-penten-2-ol (31). The cyclopropylethanol 20 2.72 g,
10 mmol) was oxidized employing the Swern procedure [13]. After the usual workup and drying
(MgSO4) the solvent was removed and the crude cyclopropylethanal 30 was immediately
dissolved in dry THF (25 mL). The resulting solution was cooled to -20 °C and kept under a N2
atmosphere. To the cyclopropylethanal-THF solution, was added dropwise a solution of
allylzinc bromide (13 mmol) in THF (20 mL). The resulting mixture was kept at -20 °C for 45
min and then the cooling bath was removed to allow the reaction to come to room temperature.
The reaction was hydrolysed by 5% H2SO4 (30 mL) and extracted with ether (3 x 25 mL). The
combined organic phase was washed with 5% NaHCO3 (3 x 25 mL), saturated NaCl (2 x 25
mL) and dried (MgSO4). The solvent was evaporated leaving viscous oil which was flash
chromatographed (silica, pet. ether/EtOAc 65:35) to give 2.2 g (71%) of the alcohol 31, as a
1
mixture of diastereomers. IR (film): 3320 (s), 3020 (w), 2995 (s), 1625 (m), 1425 (s) cm-1. H
NMR (200 MHz, CDCl3): δ 1.16 (s, 3 H), 1.25 (m, 1 H), 1.40 (s, 3 H), 1.35-1-70 (m, 2 H), 2.00
(s, 1 H), 2.10-2.45 (m, 2 H), 3.80 (m, 1 H), 5.20 (m, 2 H), 5.85 (m, 1 H).
1-(2,2-dibromo-3,3-dimethylcyclopropyl)-2-trimethylsilyloxy-4-pentene (32). To the alcohol 31
(5.35 g, 0.017 mol), kept under a N2 atmosphere, was added N-O-bis-trimethylsilylacetamide
(1.74 g, 0.0086 mol) followed by a catalytic amount of trimethylchlorosilane. The reaction was
complete in an instant. A few drops of triethylamine were added to neutralize the small amount
of HCl formed. The reaction mixture was extracted with ether, the extract washed with water
and dried (K2CO3-MgSO4). Filtration followed by evaporation of the solvent left oil which was
purified by flash chromatography (silca, pet. ether/EtOAc 65:35) to afford the 5.9 g (90%) of
the silyl ether 32. IR (film): 3020 (w), 2900 (s), 1630 (m), 1430 (s), 1360 (s), 1245 (s), 1085 (s),
830 (s), 750 (s) cm-1. 1H NMR (200 MHz, CDCl3): δ 0.15 (m, 9 H), 1.18 (s, 3 H), 1.40 (s, 3 H),
1.52-1.75 (m, 3 H), 2.27 (m, 2 H), 3.85 (m, 1 H), 5.10 (m, 2 H), 5.80 (m, 1 H).
8-Methyl-4-trimethylsilyloxynona-1,6,7-triene (33). The gem-dibromocyclopropane 32 (4.5 g,
0.012 mol), in dry ether (75 mL), was cooled to -5 °C. An ethereal solution of 1.6 M MeLi (10.9
mL, 0.0175 mol) was added dropwise with stirring. The resulting mixture was further stirred for
15 min and then quenched by dropwise addition of water (25 mL). The organic phase was
Bull. Chem. Soc. Ethiop. 2012, 26(1)

112
S.J.M. Mdachi
extracted with ether (3 x 35 mL) and the combined organic extract dried (MgSO4). Evaporation
of the solvent left an oil, which was purified by distillation to give 1.6 g (61%) of the ene-allene
33, b.p. 48-50 °C/0.1 mmHg. IR (film): 3025 (w), 2910 (s), 1965 (m), 1630 (m), 1430 (s), 1355
(s), 1250 (s), 1085 (s), 840 (s), 750 (s) cm-1. 1H NMR (200 MHz, CDCl3): δ 0.13 (s, 9 H), 1.69
(s, 3 H), 1.70 (s, 3 H), 2.15 (m, 2 H), 2.25 (m, 2 H), 3.73 (m, 1 H), 4.94 (m, 1 H), 5.05 (m, 2 H),
5.85 (m, 1 H).
8-methylnonane-1,6,7-trien-4-one (4a). To a solution of the allene 33 (2.8 g, 12.5 mmol) in
acetone (40 mL), cooled to -20 °C, was dropwise added Jones reagent (6.25 mL, 15.5 mmol).
The resulting mixture was kept at -20 °C for 15 min and then allowed to come to room
temperature (2 h). The organic phase was separated and the aqueous phase extracted with ether
(3 x 35 mL). The combined organic phase was washed as follows: 2 x 35 mL brine, 2 x 35 mL
5% aq. NaHCO3, 40 mL water and dried (MgSO4). Removal of the solvent left a yellowish oil
which was distilled to give 1.14 g (61%) of ketone 4a, b.p. 54 °C/0.05 mmHg. IR (film): 3030
(w), 2900 (s), 1965 (s), 1705 (s), 1635 (m), 1420 (s), 1390 (s), 1320 (s), 1080 (s), 990 (s), 915
(s) cm-1. 1H NMR (200 MHz, CDCl3): δ 1.66 (s, 3 H), 1.67 (s, 3 H), 3.05 (d, J 7 Hz, 2 H), 3.22
(d, J 7 Hz, 2 H), 5.05-5.20 (m, 3 H), 5.90 (m, 1 H). 13C NMR (50 MHz, CDCl3): δ 21.84, 44.39,
47.99, 82.55, 96.78, 119.12, 130.79, 202.78, 205.88.
ACKNOWLEDGEMENTS
The Norwegian Agency to International Development (NORAD) is greatly acknowledged for
fully financing this research. The Chemistry Department, University of Oslo is greatly
acknowledged for availing laboratory facilities for this research. The author would like also to
thank his colleagues in the Chemistry Department, University of Dar es Salaam for their
valuable inputs during the preparation of this paper.
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