A rapid and efficient stereoselective synthesis of (Z)- and (E)-allyl bromides from Baylis-Hillman adducts using bromo(dimethyl)sulfonium bromide

Article abstract of DOI:10.1002/hlca.200690141

Treatment of Baylis-Hillman adducts 1 with bromo(dimethyl)sulfonium bromide, Br(Me₂)S⁺Br^-, in MeCN was found to stereoselectively afford (Z)- and (E)-allyl bromides 2. The reaction is rapid at room temperature, high-yieldi

Full text of DOI:10.1002/hlca.200690141

Helvetica Chimica Acta – Vol. 89 (2006)
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A Rapid and Efficient Stereoselective Synthesis of (Z)- and (E)-Allyl
Bromides from Baylis–Hillman Adducts Using Bromo(dimethyl)sulfonium
Bromide1)
by Biswanath Das*, Katta Venkateswarlu, Maddeboina Krishnaiah, Harish Holla, and Anjoy Majhi
Organic Chemistry Division-I, Indian Institute of Chemical Technology, Hyderabad-500 007, India
(phone: +91-40-7193434; fax: +91-40-7160512; e-mail: biswanathdas@yahoo.com)
Treatment of Baylis–Hillman adducts 1 with bromo(dimethyl)sulfonium bromide, Br(Me2)S+BrÀ, in
MeCN was found to stereoselectively afford (Z)- and (E)-allyl bromides 2. The reaction is rapid at room
temperature, high-yielding, and highly stereoselective.
Introduction. – The Baylis–Hillman reaction involving the coupling of an activated
vinylic system with electrophiles in the presence of a catalytic amount of tertiary amine
(usually DABCO) is a useful carbonÀcarbon bond-forming process in synthetic
organic chemistry [1]. The resulting adducts 1 (see below), 3-hydroxy-2-methylidene-
alkanoates (derived from acrylate esters) or 3-hydroxy-2-methylidene-alkanenitriles
(derived from acrylonitrile), have frequently been used for the stereoselective synthesis
of different functionalized molecules [1b][2]. The allyl halides prepared from these
adducts have been used in the synthesis of various natural and biologically active mol-
ecules and their analogues such as a-methylidene-g-butyrolactones [2a], a-alkylidene-
b-lactams [2b], and flavonoids [2c]. The direct conversion of the Baylis–Hillman
adducts into their corresponding halides has been previously accomplished with differ-
ent halogen-containing reagents including strong acids (HBr/H2SO4, HI/H3PO4)
[2a][3a], organic acid halides (oxalyl chloride, MsCl) [3b,c], HCA/PPh3 [3a], Lewis
acids (FeCl3, InCl3) [3d,e], and metallic (Na and Li) halides [3f,g]. However, unsatis-
factory yields, low stereoselectivities, prolonged reaction times, and harsh reaction con-
ditions are often drawbacks in many of these methods.
Results and Discussion. – In continuation of our work [3d,g][4] on the synthesis of
configurationally defined, trisubstituted alkenes from Baylis–Hillman adducts, we have
recently discovered that these adducts can easily be converted into the corresponding
allyl bromides by treatment with bromo(dimethyl)sulfonium bromide (Br(Me2)S+BrÀ)
in MeCN at room temperature (Scheme 1).
Several allyl bromides were now prepared in yields of 83–99% from different Bay-
lis–Hillman adducts containing either ester (MeOOC, EtOOC) or cyano (CN) groups
(Table). The adducts with either electron-donating or withdrawing groups in the aryl
1
)
Part 81 in the series ‘Studies on Novel Synthetic Methodologies’, IICT Communication No. 060703.
© 2006 Verlag Helvetica Chimica Acta AG, Zürich

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Helvetica Chimica Acta – Vol. 89 (2006)
Scheme 1
(Ar) moiety underwent the conversion smoothly. The reaction time required for the
conversion of adducts containing aryl groups with electron-rich substituents was only
0.2–1.0 h. For aromatic substrates with electron-withdrawing groups, the reaction
time was somewhat longer (ca. 3 h).
The structures and configurations of the prepared allyl bromides were derived from
their 1H-NMR and MS data, and by comparison of the spectroscopic values with those
reported for known compounds [3f,g]. The allyl bromides were formed with excellent
stereoselectivities. The compounds with ester moieties as electron-withdrawing groups
(EWG) were obtained with (Z)-configuration, while those with CN groups were (E)-
1
configured exclusively. In the H-NMR spectrum of a trisubstituted alkene, the b-
vinylic H-atom cis and trans to the ester group is known to resonate at d(H) 7.5 and
6.5, respectively, when the substituent R is aromatic [5a,b]. The same H-atom cis
and trans to an ester group resonates at d(H) 6.8 and 5.7, respectively, when R is
alkyl [5c,d]. Similarly, the b-vinylic H-atom cis and trans to the CN group resonates
at d(H) 7.6 and 7.2, respectively, when R is aryl [3g][5e,f]; the same H-atom cis and
trans to a CN group resonates at d(H) 6.8 and 6.3, respectively, when R is alkyl
[3g][5g,h]. Based on these reported chemical shifts, the (Z)- and (E)-isomers of the
prepared allyl bromides could be readily identified.
A plausible mechanism for the above conversion is shown in Scheme 2. It involves
attack of the electron pair of the OH group of the adduct 1 to the S-atom of
Br(Me2)S+BrÀ to form species A. Then, BrÀ attacks the methylidene C=C bond,
which results in isomerization under concomitant detachment of the C(3)ÀO bond
and formation of the allyl bromide 2.
Scheme 2

Helvetica Chimica Acta – Vol. 89 (2006)
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Table. Preparation of (Z)- and (E)-Allyl Bromides 2a–o from Baylis–Hillman Adducts Using
Br(Me2)S+BrÀ . For synthetic details and compound characterization, see text and Exper. Part.
Series
R
EWGa)
Productb)
Time [h]
Yield [%]c)
a
C
G
CO2Me
G
0.3
98
b
2-ClÀC
A
0.5
93
c
4-ClÀC
N
0.5
0.5
3.0
95
90
85
d
e
3,4-(Cl)2ÀC6
U
4-O2NÀC6
f
Me(CH2)7
CH2
0.5
0.5
1.0
0.5
0.2
95
93
89
92
99
g
h
i
C6H5(CH2)2
Et
4-ClÀC
A
CO2Et
G
j
4-EtÀC
A
k
4-i-PrÀC
A
0.2
99
l
4-MeOÀC
6H5
G
0.5
0.5
1.0
94
91
88
m
n
C
U
CN
3,4-(Cl)2ÀC6
o
3-O2NÀC6H4
A
3.0
83
b
c
a) Electron-withdrawing group. ) Compounds 2h, 2j, and 2k are new products [3f,g]. ) Isolated yield.

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The configuration of the products 2 can possibly be rationalized by considering the
transition state (TS) models B–D (Figure). TS B is more favored than C when the
EWG is an ester: in this case, (Z)-products are obtained solely. However, the TS
model D is more favored than A, when the substituent is a (linear) CN group, which
gives rise to (E)-configured products.
Figure. Conformational transition-state analysis for the rationalization of the observed stereoselectivity
in the reaction leading to the allyl bromides 2. For details, see text.
Bromo(dimethyl)sulfonium bromide [6] is an inexpensive reagent that can be used
under mild reaction conditions. Previously, it was used to carry out some synthetic con-
versions [6], mainly as a catalyst, but its utility has not fully been explored yet.
In conclusion, we have developed a simple and efficient synthesis of both (Z)- and
(E)-allyl bromides from unmodified Baylis–Hillman adducts by treatment with bro-
mo(dimethyl)sulfonium bromide in MeCN at room temperature. The method is char-
acterized by mild reaction conditions, short conversion times, high yields, and excellent
stereoselectivities.
The authors thank CSIR and UGC, New Delhi, for financial assistance.
Experimental Part
General Procedure. To a soln. of the adduct 1 (5 mmol) in MeCN (5 ml), Br(Me2)S+BrÀ (6 mmol),
prepared according to [6], was added. The mixture was stirred at r.t., and the reaction was monitored
by TLC. After completion of the reaction, the solvent was removed under reduced pressure, H2O (10
ml) was added to the residue, and the mixture was extracted with AcOEt (3×10 ml). The extract was con-
centrated, and the crude residue was purified by column chromatography (SiO2; 5–10% AcOEt in hex-
ane) to afford the pure allyl bromide. Selected anal. data of some representative allyl bromides 2 are
given below.
Methyl (2Z)-2-(Bromomethyl)-3-(2-chlorophenyl)prop-2-enoate (2b). Semisolid. 1H-NMR (200
MHz, CDCl3): 7.81 (s, 1 H); 7.64 (d, J=8.0, 1 H); 7.61 (d, J=8.0, 1 H); 7.41 (t, J=8.0, 1 H); 7.22 (t,
J=8.0, 1 H); 4.15 (s, 2 H); 3.81 (s, 3 H). EI-MS: 292, 290, 288 (M+). Anal. calc. for C11H10BrClO2:
C 45.67, H 3.46; found: C 45.72, H 3.40.
1
Methyl (2Z)-2-(Bromomethyl)pent-2-enoate (2h). Semisolid. H-NMR (200 MHz, CDCl3): 6.94 (t,
J=7.0, 1 H); 4.21 (s, 2 H); 3.83 (s, 3 H); 2.31 (q, J=7.0, 2 H); 0.83 (t, J=7.0, 3 H). EI-MS: 208, 206
(M+). Anal. calc. for C7H11BrO2: C 40.58, H 5.31; found: C 40.69, H 5.25.

Helvetica Chimica Acta – Vol. 89 (2006)
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Ethyl (2Z)-2-(Bromomethyl)-3-(4-ethylphenyl)prop-2-enoate (2j). Semisolid. 1H-NMR (200 MHz,
CDCl3): 7.76 (s, 1 H); 7.49 (d, J=8.0, 2 H); 7.28 (d, J=8.0, 2 H); 4.38 (s, 2 H); 4.30 (q, J=7.0, 2 H);
2.70 (q, J=7.0, 2 H); 1.39 (t, J=7.0, 3 H); 1.28 (t, J=7.0, 3 H). EI-MS: 298, 296 (M+). Anal. calc. for
C14H17BrO2: C 56.57, H 5.72; found: C 56.64, H 5.63.
Ethyl (2Z)-2-(Bromomethyl)-3-[4-(1-methylethyl)phenyl]prop-2-enoate (2k). Semisolid. 1H-NMR
(200 MHz, CDCl3): 7.75 (s, 1 H); 7.52 (d, J=8.0, 2 H); 7.30 (d, J=8.0, 2 H); 4.39 (s, 2 H); 4.32 (q,
J=7.0, 2 H); 2.93 (m, 1 H); 1.40 (t, J=7.0, 3 H); 1.27 (d, J=7.0, 6 H). EI-MS: 312, 310 (M+). Anal.
calc. for C15H19BrO2: C 57.88, H 6.11; found: C 57.94, H 6.08.
(2E)-2-(Bromomethyl)-3-(3-nitrophenyl)prop-2-enenitrile (2o). Semisolid. 1H-NMR (200 MHz,
CDCl3): 8.46 (d, J=2.0, 1 H); 8.33 (dd, J=8.0, 2.0, 1 H); 8.28 (dd, J=8.0, 2.0, 1 H); 7.68 (dd, J=8.0,
2.0, 1 H); 7.21 (s, 1 H), 4.20 (s, 2 H). EI-MS: 268, 266 (M+). Anal. calc. for C10H7BrN2O2: C 44.94, H
2.62; found: C 44.72, H 2.64.
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Received May 29, 2006