Synthetic applications of the Baylis-Hillman reaction: Simple and convenient synthesis of five important insect pheromones

Article abstract of DOI:10.1002/hlca.200690090

A simple and convenient synthesis of five important insect pheromones by means of Baylis-Hillman adducts is described, i.e., of (2E,4S)-2,4-dimethylhex- 2-enoic acid (1), a mandibular-gland secretion of the male carpenter ant in the genus Camponotus, of (+)-(S)-manicone (2) and (+)-(S)-normanicone (3), two mandibular-gland constituents of Manica ants, and of (+)-dominicalure-I (6) and (+)-dominicalure-II (7), two aggregation pheromones of the lesser grain borer Rhyzopertha dominion (F). For the first time, the potential of the Baylis-Hillman chemistry for the stereoselective synthesis of trisubstituted olefins was successfully applied to the synthesis of these pheromone compounds.

Full text of DOI:10.1002/hlca.200690090

876
Helvetica Chimica Acta – Vol. 89 (2006)
Synthetic Applications of the Baylis–Hillman Reaction: Simple and
Convenient Synthesis of Five Important Insect Pheromones1)
by Biswanath Das*, Joydeep Banerjee, Nikhil Chowdhury, Anjoy Majhi, and Gurram Mahender
Organic Chemistry Division – I, Indian Institute of Chemical Technology, Hyderabad – 500 007, India.
(fax : (+91)-40-7160512; e-mail: biswanathdas@yahoo.com)
A simple and convenient synthesis of five important insect pheromones by means of Baylis–Hillman
adducts is described, i.e., of (2E,4S)-2,4-dimethylhex-2-enoic acid (1), a mandibular-gland secretion of the
male carpenter ant in the genus Camponotus, of (+)-(S)-manicone (2) and (+)-(S)-normanicone (3), two
mandibular-gland constituents of Manica ants, and of (+)-dominicalure-I (6) and (+)-dominicalure-II
(7), two aggregation pheromones of the lesser grain borer Rhyzopertha dominica (F). For the first
time, the potential of the Baylis–Hillman chemistry for the stereoselective synthesis of trisubstituted ole-
fins was successfully applied to the synthesis of these pheromone compounds.
Introduction. – Trisubstituted alkene moieties have been widely observed in several
natural bioactive compounds including different pheromones and antibiotics [1]. The
biological properties of these alkenes are remarkably dependent on the configuration
of the C=C bond [2]. A number of methods have been developed for the stereoselec-
tive synthesis of trisubstituted alkenes [2–6]. As a part of our research program on the
synthetic application of the Baylis–Hillman reactions [7–9], we herein report the sim-
ple and convenient synthesis of five important insect pheromones, i.e., of (2E,4S)-2,4-
dimethylhex-2-enoic acid (1), a caste-specific substance present in the mandibular
glands of the male carpenter ants in the genus Camponotus [10], of (+)-(S)-manicone
(2) and (+)-(S)-normanicone (3), the mandibular-gland alarm pheromone components
of the ants in the genus Manica [11][12], and of (+)-(1S)-1-methylbutyl (2E)-2-meth-
ylpent-2-enoate (=dominicalure-I; 6) and (+)-(1S)-1-methylbutyl (2E)-2,4-dimethyl-
pent-2-enoate (=dominicalure-II; 7), the aggregation pheromones of the lesser grain
borer Rhyzopertha dominica (F) [13].
The Baylis-Hillman reaction is a versatile CÀC bond forming reaction providing
synthetically useful multifunctional adducts [14]. These adducts have been successfully
utilized for the stereoselective synthesis of various naturally occurring bioactive mole-
cules [14b][15–18]. Most of these molecules contain a configurationally defined trisub-
stituted C=C bond as the key structural unit which has been well documented in the
literature [14b].
Despite these substantial advances in synthetic applications of the Baylis–Hillman
chemistry, to the best of our knowledge, this is the first report2) on the syntheses of the
1
)
)
Part 25 in the series, ꢀSynthetic studies on natural productsꢁ.
2
Only the synthesis of racemic compound (Æ)-1 from a Baylis–Hillman adduct has been reported ear-
lier [6d].
ꢂ 2006 Verlag Helvetica Chimica Acta AG, Zürich

Helvetica Chimica Acta – Vol. 89 (2006)
877
chiral pheromones 1–3, 6, and 7 exploring the immense potential of Baylis–Hillman
adducts for the stereoselective generation of trisubstituted alkene moieties. These chi-
ral pheromones were mainly selected as synthetic targets because of the presence of an
(E)-configurated C=C bond in their structures which can easily be accessed via Baylis–
Hillman adducts and which ultimately is responsible for the observed biochemical sig-
nalling [4a,b][5b,c][10–13]. Very recently we have developed an efficient and facile
stereoselective synthesis [9] of (2E)-2-methylalk-2-enoates directly from unmodified
Baylis–Hillman adducts using inexpensive NaBH4 as hydride donor in the presence
of CuCl2 ·2H2O in MeOH at room temperature (Scheme 1).
Scheme 1. Stereoselective Synthesis of (2E)-2-Methylalk-2-enoates
While we completed the above work [9], Fernandes et al. [6d] reported a synthesis
of (Æ)-1 by zinc-mediated reduction of a modified version3) of the Baylis–Hillman
adduct in four steps. The asymmetric synthesis [5c] of pheromone 1 in six steps starting
from (2S)-2-methylbutCAHTREaUNG nal has been reported, but the overall yield was low. Moreover,
generation of the (E)-configuration of the C=C bond and the methylation at the 2-posi-
tion were associated with a number of by-products [5c]. Being aware of the potential of
our methodology [9], we planned a one-pot two-step synthesis of compound 1 directly
from an unmodified Baylis–Hillman adduct4) [19], which would compare favorably
with the previously reported multistep transformations [4a,b][5b,c][6d] and rather tedi-
ous experimental protocols and complex reagents [5b,c][6d].
3
)
A number of methodologies have been developed for the reduction of acetyl and allyl bromide deriv-
atives (modified versions) of Baylis–Hillman adducts [14b][15b,c].
The conversion of unmodified Baylis–Hillman adducts is more convenient and represents an atom
economy as compared to that of modified adducts.
4
)

878
Helvetica Chimica Acta – Vol. 89 (2006)
Considerable efforts have been reported for the synthesis of (Æ)-2 [4a,b][5b][20] as
well as of chiral (+)-manicone (2) [5c][21], but only one synthesis of (+)-normanicone
(3) is known [21b]. However, in most of these syntheses, the control of the two config-
urational factors, i.e., (2E,4S) required multistep sequences [5c][21] with low overall
yields [5c][21b] or resulted in moderate optical purity [21a].
In this report, starting from (2S)-2-methylbutanal (obtained in [5c] after six steps),
we describe a three-step synthesis of (2E,4S)-2,4-dimethylhex-2-enoic acid (1) and a
five-step common synthesis route (via 1) of both (+)-(S)-manicone (2) and (+)-(S)-nor-
manicone (3) (Scheme 2). Similarly, (+)-dominicalure-I (6) and (+)-dominicalure-II
(7) were also efficiently synthesized with entire (E)-selectivity, high overall yields,
and optical purity (Scheme 3). Thus, we explored the Baylis–Hillman adduct as a pow-
erful intermediate for the synthesis of a series of pheromones. The latter could be
employed as naturally occurring biological attractants, thus avoiding to resort to
large amounts of contact insecticides and fumigants as well as avoiding the environ-
mental problems associated with the use of the latter [22][23].
Results and Discussion. – For the synthesis of pheromones 1–3 according to our
protocol [9], the Baylis–Hillman adduct 4 was needed (Scheme 2). Starting from
(2S)-2-methylbutanal [5c], Fernandes et al. have applied a number of reported methods
to accelerate the transformation to 4 [6d] and to enhance its yield, but they failed.
Moreover, a prolonged (20days) exposure of the optically active aldehyde to a large
excess of base like 1,4-diazabicylo[2.2.2]octane (DABCO; 2–3 equiv.) caused racemi-
zation of the aldehyde5) [6d][24]. To overcome this problem, we followed the recently
reported protocol for the asymmetric Baylis–Hillman reaction of a-branched chiral
aldehydes in presence of 50mol-% of DABCO in CH 2CATHERCUNG l2 ACHTREaUNG t room temperature [25].
With this protocol, we achieved a 51% yield of adduct 4, isolated as an inseparable mix-
ture of two diastereoisomers after 22 h. To enhance the yield of 4 without impairing the
optical activity, we made several attempts to synthesize 4 within shorter time, based on
methods published in a thorough literature survey [14b]. We thus established that the
key factors for an improvement of the yield of 4 within hours without hampering the
optical activity are a lower temperature (08) [26], an excess of methyl acrylate (=meth-
yl prop-2-enoate; 3 equiv.)6) [27a], and a moderate amount of DABCO (50–100mol-
%) [27]. Moreover, self-aldolization of the starting a-branched aldehydes [26] is sup-
pressed at 08. Indeed, under such optimized conditions, 4 was obtained in 71% yield
as syn/anti diastereoisomers mixture in 2.3 :1 after 20h. The configuration of the prod-
ucts was assigned by the 1H-NMR shifts and coupling constants of HÀC(3) and HÀC(4)
[28].
The Baylis–Hillman adducts 8a (R=Et) and 8b (R=iPr) were prepared in 83 and
78% yield by treatment of propanal and 2-methylpropanal, respectively, with methyl
acrylate (3 equiv.) in the presence of 100 mol-% DABCO in dioxane/water 1:1, accord-
ing to the procedure described in the literature [14b][27a] (Scheme 3).
5
)
)
Racemization of chiral aldehydes on prolonged exposure to DABCO has been reported earlier [24].
The option of using an excess of acrylate in the Baylis–Hillman reaction reported in [25] was not pos-
sible since the reaction was intramolecular.
6

Helvetica Chimica Acta – Vol. 89 (2006)
Scheme 2. Synthesis of Pheromones 1–3
879
Scheme 3. Synthesis of Pheromones 6 and 7
Following our reported method [9], the Baylis–Hillman adducts 4, 8a, and 8b were
then treated with NaBH4 in the presence of CuCl2 ·2H2A
O7) in MeOH, and the inter-
CTHREUNG
mediate methyl (2E)-2-methylalk-2-enoates, present in a slightly alkaline medium
after reduction, were hydrolyzed by 10% NaOH in MeOH in the same reaction vessel8)
to afford, after workup, 1, 9a, and 9b in 78, 76, and 75% yield, respectively (Schemes 2
7
)
)
A comparable result could be obtained by using CuCl in the same proportions.
Such a one-pot procedure for the reduction/alkaline hydrolysis was not applicable to the transforma-
tion described in [6d] due to the highly acidic reduction conditions.
8

880
Helvetica Chimica Acta – Vol. 89 (2006)
and 3). No attempt was made to separate the diastereoisomers of 4 since the reduction
removed the stereogenic center at C(3).
The pheromone (2E,4S)-2,4-dimethylhex-2-enoic acid (1) was then converted to the
corresponding acid chloride 5 with thionyl chloride. Treatment of 5 with lithium dieth-
ylcuprate or lithium dimethylcuprate in Et
2A
pounds (+)-(S)-manicone (2) and (+)-(S)-normanicone (3) in 85 and 82% isolated
yield, respectively (Scheme 2). On the other hand, the 2-methylalk-2-enoic acids 9a
and 9b were esterified with (+)-(2S)-pentan-2-ol to furnish the two other target mole-
cules 6 and 7, respectively, with high overall yields and optical purity (Scheme 3).
In conclusion, we successfully applied the potential of Baylis–Hillman chemistry to
the synthesis of five pheromones in high overall yield and optical purity, i.e., of (2E,4S)-
2,4-dimethylhex-2-enoic acid (1), (+)-(S)-manicone (2), (+)-(S)-normanicone (3), (+)-
(1S)-1-methylbutyl (2E)-2-methylpent-2-enoate (=dominicalure-I; 6) and (+)-(1S)-1-
methylbutyl (2E)-2,4-dimethylpent-2-enoate (=dominicalure-II; 7). Our straightfor-
ward strategy of deriving (2E)-2-methylalk-2-enoic acids from unmodified Baylis–Hill-
man adducts is simple, inexpensive, and perfectly stereoselective compared to the pre-
vious approaches. Optimized reaction conditions were developed for the preparation of
the important optically active Baylis–Hillmann adduct 4. The scope of this route can
easily be extended to the synthesis of other related bioactive molecules.
The authors thank UGC and CSIR, New Delhi, for financial assistance.
Experimental Part
1. General. The Baylis–Hillman adducts 8a and 8b were prepared according to [27a]. (+)-(2S)-pen-
tan-2-ol was purchased from Lancaster Chemicals Company. CC=Column chromatography; FC=flash
chromatography. Optical rotations: Jasco P-1020 polarimeter. IR Spectra: Perkin-Elmer-1310 spectro-
photometer; n in cmÀ1. NMR Spectra: Varian Gemini 200 MHz (1H) and Bruker-UXNMR 75 MHz
~
(13C); d in ppm, J in Hz. LC-MS: Agilent-1100-LC/MSD Trap SL in the pos. mode; in m/z. Elemental
analyses: Perkin-Elmer-240C-CHN analyzer.
2. Baylis–Hillman Adducts. Methyl (3R,4S)- and (3S,4R)-3-Hydroxy-4-methyl-2-methylenehexanoate
(4). A soln. of (2S)-2-methylbutanal ([a]D24 =+34.81 ([5c]: [a]2D4 =+34.33 (neat)); 2.16 ml, 20mmol) and
methyl acrylate (5.36 ml, 60mmol) in dioxane (20ml) was cooled to 0 8 in an ice bath, and DABCO (1.12
g, 10mmol, 50mol-%) was added. After completion of the reaction (20h; TLC monitoring), tBuOMe
(150ml) and 5% aq. HCl soln. (50ml) were added. The aq. phase was extracted with Et 2ACHTREOUGN (2”50ml),
the combined org. phase dried (Na2SO4), and evaporated, and the resulting residue purified by CC
(5% AcOEt/hexane): 4 (2.44 g, 71%) as an inseparable syn/anti mixture 2.3 :1. Colorless oil. IR
1
(KBr): 3485, 2965, 2932, 2880, 1726, 1631. H-NMR (200 MHz, CDCl3): 0.80–0.96 (m, 6 H); 1.09–1.21
(m, 1.4 H, syn); 1.35–1.51 (m, 0.6 H, anti); 1.59–1.76 (m, 1 H); 2.60( d, J=6.5, 0.7 H, syn); 2.83 (d,
J=8.0, 0.3 H, anti); 3.76 (s, 3 H); 4.08 (t, J=8.0, 0.3 H, anti); 4.30( t, J=6.5, 0.7 H, syn); 5.74 (s, 0.3 H,
anti); 5.79 (s, 0.7 H, syn); 6.24 (s, 0.3 H, anti); 6.27 (s, 0.7 H, syn). 13C-NMR (75 MHz, CDCl3): syn isomer:
11.9; 13.4; 26.8; 39.0; 52.0; 74.7; 125.6; 142.3; 167.3; anti isomer: 11.5; 16.0; 24.5; 39.5; 52.0; 76.8; 126.3;
141.9; 167.5. LC-MS: 173 ([M+1]+). Anal. calc. for C9H16O3: C 62.79, H 9.30; found: C 62.70, H 9.34.
Methyl 3-Hydroxy-2-methylenepentanoate (8a). A soln. of propanal (1.45 ml, 20mmol) and methyl
acrylate (5.36 ml, 60mmol) in dioxane/H 2O 1:1 (50ml) was stirred at r.t. in the presence of DABCO
t
(100 mol-%, 2.24 g, 20 mmol). Upon completion of the reaction (TLC monitoring), BuOMe (500 ml)
and H2O (150ml) were added. The org. phase was washed with brine (2”80ml), dried (Na 2SO4), and
evaporated, and the resulting residue purified by CC (4% AcOEt/hexane): 8a (2.39 g, 83%). Colorless

Helvetica Chimica Acta – Vol. 89 (2006)
881
oil. IR (KBr): 3438, 2967, 2880, 1715, 1630, 1440. 1H-NMR (200 MHz, CDCl3): 0.92 (t, J=7.0, 3 H);
1.51–1.73 (m, 2 H); 3.08 (br., 1 H); 3.75 (s, 3 H); 4.32 (t, J=7.0, 1 H); 5.81 (s, 1 H); 6.20( s, 1 H). LC-
MS: 145 ([M+1]+). Anal. calc. for C7H12O3: C 58.33, H 8.33; found: C 58.42, H 8.28.
Methyl 3-Hydroxy-4-methyl-2-methylenepentanoate (8b). As described for 8a, from 2-methylpropa-
nal (1.81 ml, 20mmol): 8b (2.46 g, 78%). Colorless oil. IR (KBr): 3525, 2959, 2875, 1726, 1630, 1440. 1H-
NMR (200 MHz, CDCl3): 0.88 (d, J=7.0, 3 H); 0.93 (d, J=7.0, 3 H); 1.82–1.98 (m, 1 H); 2.32 (br., 1 H);
3.77 (s, 3 H); 4.04 (d, J=7.0, 1 H); 5.75 (s, 1 H); 6.22 (s, 1 H). LC-MS: 159 ([M+1]+). Anal. calc. for
C8H14O3: C 60.76, H 8.86; found: C 60.68, H 8.93.
3. One-pot Preparation of (2E)-2-Methylalk-2-enoic Acids: General Procedure [9]. The Baylis–Hill-
man adduct (10mmol) and CuCl 2 ·2H2O (2.56 g, 15 mmol) were dissolved in MeOH (30ml), and the
mixture was stirred for 10min at 0 8. NaBH4 (0.58 g, 15 mmol) was added in portions with stirring (vig-
orous gas evolution). Stirring was continued for 30min until gas evolution ceased. To the resulting
slightly alkaline soln., 40% NaOH/MeOH (10 ml) was added dropwise while cooling in an ice bath
and maintaing an overall alkali concentration of 10%. Then the mixture was stirred for 12 h at 258.
After the addition of H2O (80ml), the mixture was washed with Et
2ACHTREUONG (2”50ml). Then the aq. phase
was acidified to pH 2 with 10% HCl soln. and extracted with Et2AO (3”50ml). The extract was washed
CTHREUNG
with brine, dried (Na2SO4), and evaporated: (2E)-2-methylalk-2-enoic acid.
(2E,4S)-2,4-Dimethylhex-2-enoic Acid (1): Yield 1.1 g (78% from 4). Colorless oil. [a]2D4 =+35.13
(c=2.696, benzene) ([29]: [a]2D4 =+34.6 (c=2.65, benzene)). IR (KBr): 3419, 2964, 2927, 2875, 1688,
1
1640. H-NMR (200 MHz, CDCl3): 0.88 (t, J=7.0, 3 H); 1.03 (d, J=7.0, 3 H); 1.35–1.44 (m, 2 H); 1.85
(d, J=1.5, 3 H); 2.40–2.49 (m, 1 H); 6.71 (dd, J=10.0, 1.5, 1 H). 13C-NMR (75 MHz, CDCl3): 10.9;
12.5; 18.0; 29.0; 33.8; 125.2; 149.5; 173.6. LC-MS: 143 ([ M+1]+). Anal. calc. for C8H14O2: C 67.60, H
9.86; found: C 67.71, H 9.79.
(2E)-2-Methylpent-2-enoic Acid (9a): Yield 0.866 g (76% from 8a). Colorless oil. IR (KBr): 3450,
1
2929, 1690, 1639. H-NMR (200 MHz, CDCl3): 1.20( t, J=7.0, 3 H); 1.80 (s, 3 H); 2.14–2.33 (m, 2 H);
6.88 (t, J=7.0, 1 H); 11.6 (br. s, 1 H). 13C-NMR (75 MHz, CDCl3): 11.9; 13.0; 22.4; 126.9; 146.8; 174.4.
LC-MS: 115 ([M+1]+). Anal. calc. for C6H10O2: C 63.15, H 8.77; found: C 63.24, H 8.88.
(2E)-2,4-Dimethylpent-2-enoic Acid (9b): Yield 0.958 g (75% from 8b). Colorless oil. IR (KBr): 3417,
2925, 1696, 1618. 1H-NMR (200 MHz, CDCl3): 1.08 (d, J=7.0, 6 H); 1.81 (d, J=1.5, 3 H); 2.59–2.78 (m, 1
H); 6.74 (dd, J=10.5, 1.5, 1 H). 13C-NMR (75 MHz, CDCl3): 11.8; 21.9; 26.0; 125.2; 151.6; 174.3. LC-MS:
129 ([M+1]+). Anal. calc. for C7H12O2: C 65.62, H 9.37; found: C 65.54, H 9.42.
4. (2E,4S)-2,4-Dimethylhex-2-enoyl Chloride (5). A soln. of 1 (1 g, 7 mmol) in benzene (10ml) was
added to a stirred soln. of SOCl2 (2.12 g, 18 mmol) in benzene (10ml), and the resulting mixture was
refluxed for 2 h, then cooled, and evaporated: crude 5 (1.127 g, 100%) which was used in the next step
without further purification.
5. (4E,6S)-4,6-Dimethyloct-4-en-3-one (2). A 1.56M EtLi soln. in Et
to a stirred suspension of CuI (1.14 g, 6 mmol) and Et2A
O (10ml) cooled to À408. After stirring for 15 min,
the mixture was cooled to À788 and a soln. of 5 (560mg, 3.5 mmol) in Et 2AO (5 ml) was dropwise added.
After stirring for 15 min at À788, MeOH (5 ml) was added, and the mixture was allowed to warm to r.t.,
then poured into a large excess of sat. aq. NH4Cl soln., and extracted with Et2AO. The org. extract was
2ACHTREOUNG (7.7 ml, 12 mmol) was added
CTHREUNG
CTHREUNG
CTHREUNG
washed with aq. NH4Cl soln., dried, and evaporated and the residue purified by FC (silica gel, 7%
AcOEt/hexane): 2 as (458 mg, 85%). Colorless oil. [a]2D4 =+44.11 (c=4.86, Et
2A
1
(c=5, Et
2A
J=6.4, 3 H); 1.10( t, J=7.3, 3 H); 1.26–1.51 (m, 2 H); 1.79 (d, J=1.5, 3 H); 2.43–2.52 (m, 1 H); 2.69
(q, J=7.3, 2 H); 6.38 (dd, J=1.5, 9.8, 1 H). 13C-NMR (75 MHz, CDCl3): 8.9; 11.3; 12.0; 19.9; 29.5;
29.9; 35.5; 135.8; 147.8; 202.9. LC-MS: 155 ([M+1]+). Anal. calc. for C10H18O: C 77.92, H 11.68;
found: C 77.81, H 11.59.
(3E,5S)-3,5-Dimethylhept-3-en-2-one (3). As described for 2, with 1.6M MeLi soln. in Et
mmol), CuI (1.14 g, 6 mmol) in Et2AO, and 5 (560mg, 3.5 mmol) in Et 2AO: 3 (402 mg, 82%). Colorless oil.
[a]2D4 =+38.09 (c=4.24, Et O) ([21b]: [a]2D4 =+37.60( c=5, Et O)). IR (KBr): 1686, 1638, 1461. 1H-NMR
2A 2A
(200 MHz, CDCl3): 0.88 (t, J=7.5, 3 H); 1.03 (d, J=6.4, 3 H); 1.25–1.50( m, 2 H); 1.77 (d, J=1.5, 3 H);
2ACHTREOUGN (7.5 ml, 12
C
CHTREUNG
C
CHTREUNG

882
Helvetica Chimica Acta – Vol. 89 (2006)
2.29 (s, 3 H); 2.42–2.51 (m, 1 H); 6.32 (dd, J=1.5, 9.8, 1 H). 13C-NMR (75 MHz, CDCl3): 11.6; 12.1; 20.2;
25.8; 30.0; 35.8; 136.7; 149.3; 200.0. LC-MS: 141 ([M+1]+). Anal. calc. for C9H16O: C 77.14, H 11.43;
found: C 77.23, H 11.47.
6. Esterification of (2E)-2-Methylalk-2-enoic Acids: General Procedure. A mixture of (2E)-2-meth-
ylalk-2-enoic acid (2 mmol) and thionyl chloride (354 mg, 3 mmol) was refluxed for 30min. The excess
thionyl chloride was evaporated and the residual acid chloride treated with (+)-(2S)-pentan-2-ol (3
mmol) at 508 for 30min. The mixture was diluted with Et
dried, and evaporated and the crude oil subjected CC: ester.
(+)-(1S)-1-Methylbutyl (2E)-2-Methylpent-2-enoate (6): 0.250 g (68%). Colorless oil. [a]2D4 =+13.9
(c=1.173, Et2A 2A
O) ([13]: [a]2D4 =+13.4 (c=0.175, Et O)). IR (KBr): 2964, 1709, 1618. 1H-NMR (200
2ACHTREOUGN (50ml), washed with brine (3”10ml),
C
CHTREUNG
MHz, CDCl3): 0.90 (t, J=7.5, 3 H); 1.06 (t, J=7.0, 3 H); 1.22 (d, J=7.0, 3 H); 1.28–1.63 (m, 4 H);
1.80( d, J=1.6, 3 H); 2.07–2.22 (m, 2 H); 4.82–4.98 (m, 1 H); 6.65 (dt, J=7.0, 1.6, 1 H). 13C-NMR (75
MHz, CDCl3): 12.8; 13.7; 17.1; 18.6; 19.9; 22.1; 36.0; 70.1; 127.8; 143.2; 167.9. LC-MS: 185 ([ M+1]+).
Anal. calc. for C11H20O2: C 71.74, H 10.87; found: C 71.66, H 10.77.
(+)-(1S)-1-Methylbutyl (2E)-2,4-Dimethylpent-2-enoate (7): 0.273 g (69%). Colorless oil.
1
[a]2D4 =+11.4 (c=1.632, Et
C
O)). IR (KBr): 2926, 2855, 1736. H-
NMR (200 MHz, CDCl3): 0.91 (t, J=7.0, 3 H); 1.05 (d, J=7.0, 6 H); 1.09 (d, J=7.0, 3 H); 1.22–1.40
(m, 4 H); 1.83 (d, J=1.5, 3 H); 2.58–2.64 (m, 1 H); 4.84–4.96 (m, 1 H); 6.48 (dd, J=10.5, 1.5, 1 H).
13C-NMR (75 MHz, CDCl3): 13.9; 18.8; 19.2; 20.5; 21.5; 22.2; 38.1; 70.8; 126.1; 148.3; 168.2. LC-MS:
199 ([M+1]+). Anal. calc. for C12H22O2: C 72.73, H 11.11; found: C 72.79, H 11.23.
REFERENCES
[1] J. W. S. Bradshaw, R. Baker, P. E. Howse, Nature (London) 1975, 258, 230; M. J. Garson, Chem.
Rev. 1993, 93, 1699; M. A. DꢁAuria, L. Minale, R. Riccio, Chem. Rev. 1993, 93, 1839.
[2] A. Marfat, P. R. McGuirk, P. Helquist, J. Org. Chem. 1979, 44, 3888.
[3] Y. Masaki, K. Sakuma, K. Kaji, J. Chem. Soc., Chem. Commun. 1980, 434; H. C. Brown, D. Basa-
vaiah, J. Org. Chem. 1982, 47, 5407; S. E. Denmark, J. Amburgey, J. Am. Chem. Soc. 1993, 115,
10386; L. Navarre, S. Darses, J. P. Genet, J. Chem. Soc., Chem. Commun. 2004, 1108; H. Amri,
M. Rambaud, J. Villieras, Tetrahedron 1990, 46, 3535.
[4] a) J. A. Katzenellenbogen, T. Utawanit, J. Am. Chem. Soc. 1974, 96, 6153; b) P. J. Kocienski, J. N.
Ansell, R. W. Ostrow, J. Org. Chem. 1976, 41, 3625; c) J. A. Miller, G. Zweifel, J. Am. Chem. Soc.
1981, 103, 6217.
[5] a) R. Rossi, A. Carpita, T. Messeri, Synth. Commun. 1992, 22, 603; b) P. Coutrot, A. Ghribi, Syn-
thesis 1986, 790; c) R. Rossi, A. Carpita, P. Cossi, Tetrahedron 1992, 48, 8801.
[6] a) D. Basavaiah, M. Krishnamacharyulu, R. S. Hyma, P. K. S. Sarma, N. Kumaragurabaran, J. Org.
Chem. 1999, 64, 1197; b) U. Shadakshari, S. K. Nayak, Tetrahedron 2001, 57, 4599; c) J. Li, W. Qian,
Y. Zhang, Tetrahedron 2004, 60, 5793; d) L. Fernandes, A. J. Bortoluzzi, M. M. Saꢁ, Tetrahedron
2004, 60, 9983.
[7] B. Das, J. Banerjee, N. Ravindranath, B. Venkataiah, Tetrahedron Lett. 2004, 45, 2425; B. Das, J.
Banerjee, N. Ravindranath, Tetrahedron 2004, 60, 8357.
[8] B. Das, J. Banerjee, G. Mahender, A. Majhi, Org. Lett. 2004, 6, 3349; B. Das, G. Mahender, N.
Chowdhury, J. Banerjee, Synlett 2005, 1000.
[9] B. Das, J. Banerjee, A. Majhi, G. Mahender, Tetrahedron Lett. 2004, 45, 9225.
[10] J. M. Brand, R. M. Duffield, J. G. MacConnell, M. S. Blum, H. M. False, Science (Washington, D.C.)
1973, 179, 388.
[11] H. M. Fales, M. S. Blum, R. M. Crewe, J. M. Brand, J. Insect. Physiol. 1972, 18, 1077.
[12] H. J. Bestmann, A. B. Attygalle, J. Glasbrenner, R. Riemer, O. Vostrowsky, Angew. Chem., Int. Ed.
Engl. 1987, 26, 784.
[13] H. J. William, R. M. Silverstein, W. E. Burkholder, A. Khorramshahi, J. Chem. Ecol. 1981, 7, 759; L.
Lin-Yu, L. Guo-Qiang, J. Chem. Ecol. 1990, 16, 1921.
[14] a) A. B. Baylis, M. E. D. Hillman, German Patent 2155113, 1972; Chem. Abstr. 1972, 77, 34174q; b)
D. Basavaiah, A. J. Rao, T. Satyanarayana, Chem. Rev. 2003, 103, 811 and ref. cit. therein.

Helvetica Chimica Acta – Vol. 89 (2006)
883
[15] a) H. M. R. Hoffmann, J. Rabe, Angew. Chem., Int. Ed. Engl. 1985, 24, 94; b) H. M. R. Hoffmann, J.
Rabe, J. Org. Chem. 1985, 50, 3849; c) D. Basavaiah, N. Kumaragurubaran, Tetrahedron Lett. 2001,
42, 477; d) S. E. Drewes, N. D. Emslie, J. Chem. Soc., Perkin Trans. 1 1982, 2079.
[16] W. R. Roush, B. B. Brown, J. Org. Chem. 1993, 58, 2151; T. Jenn, D. Heissler, Tetrahedron 1998, 54,
97.
[17] D. Grassi, V. Lippuner, M. Aebi, J. Brunner, A. Vasella, J. Am. Chem. Soc. 1997, 119, 10992.
[18] C. R. Mateus, M. P. Feltrin, A. M. Costa, F. Cohello, W. P. Almedia, Tetrahedron 2001, 57, 6901; D.
Basavaiah, R. S. Hyma, Tetrahedron 1996, 52, 1253.
[19] B. M. Trost, Science (Washington, D.C.) 1991, 254, 1471.
[20] A. Alexakis, A. Commercon, C. Coulentianos, J. F. Normant, Tetrahedron 1964, 40, 715; R. Yoneda,
S. Harusawa, T. Kurihara, J. Chem. Soc., Perkin Trans. 1 1988, 3163.
[21] a) T. Mimura, Y. Kimura, T. Nakai, Chem. Lett. 1979, 1361; b) V. Martischonok, G. G. Melikyan, A.
Mineif, O. Vostrowsky, H. J. Bestmann, Synthesis 1991, 560; c) N. De Kimpe, W. Aelterman, Tetra-
hedron 1996, 52, 12815.
[22] H. A. U. Monro, E. Upitis, E. J. Bond, J. Stored Prod. Res. 1972, 8, 199.
[23] C. J. Lloyd, J. Stored Prod. Res. 1973, 9, 77.
[24] S. E. Drews, A. A. Khan, K. Rowland, Synth. Commun. 1993, 23, 183.
[25] P. Radhakrishna, V. Kannan, G. V. M. Sharma, J. Org. Chem. 2004, 69, 6467.
[26] S. Rafel, J. W. Leahy, J. Org. Chem. 1997, 62, 1521.
[27] a) C. Yu, B. Liu, L. Hu, J. Org. Chem. 2001, 66, 5413; b) P. Radhakrishna, A. Manjuvani, E. Raja
Sekhar, ARKIVOC 2005, III, 99.
[28] C. H. HeathCock, in ꢀAsymmetric Synthesisꢁ, Vol. 3, Ed. J. D. Morrison, Academic Press, Orlando,
1984, p. 111–118.
[29] N. Slogui, G. Rousseau, J. M. Conia, Synthesis 1982, 58.
Received December 29, 2005