Facile stereoselective synthesis of (E)- and (Z)-allyl bromides from the Baylis-Hillman adducts using MgBr2

Article abstract of DOI:10.1081/SCC-100104426

A simple and convenient synthesis of the title compounds is described.

Full text of DOI:10.1081/SCC-100104426

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FACILE STEREOSELECTIVE SYNTHESIS OF (E)- AND
(Z)-ALLYL BROMIDES FROM THE BAYLIS-HILLMAN
ADDUCTS USING MgBr2
Subramanian Ravichandran a
a School of Chemistry, University of Hyderabad , Hyderabad, 500 046, India
Published online: 09 Nov 2006.
To cite this article: Subramanian Ravichandran (2001) FACILE STEREOSELECTIVE SYNTHESIS OF (E)- AND (Z)-ALLYL
BROMIDES FROM THE BAYLIS-HILLMAN ADDUCTS USING MgBr2 , Synthetic Communications: An International Journal for
Rapid Communication of Synthetic Organic Chemistry, 31:13, 2059-2062, DOI: 10.1081/SCC-100104426
To link to this article: http://dx.doi.org/10.1081/SCC-100104426
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SYNTHETIC COMMUNICATIONS, 31(13), 2059–2062 (2001)
FACILE STEREOSELECTIVE SYNTHESIS
OF (E)- AND (Z)-ALLYL BROMIDES FROM
THE BAYLIS-HILLMAN ADDUCTS
USING MgBr2
Subramanian Ravichandran
School of Chemistry, University of Hyderabad,
Hyderabad – 500 046, India
ABSTRACT
A simple and convenient synthesis of the title compounds is
described.
(2Z)-2-(Bromomethyl)alk-2-enoates are versatile building blocks for
stereoselective synthesis of natural products such as necic acid, a-methylene-
g-butyrolactones and a-alkylidene-b-lactams.These fascinating compounds
have been synthesized from Baylis-Hillman reaction products, i.e. methyl-
3-hydroxy-2-methylenealkanoates using NEt3/MsCl,1 CuBr2/silica gel,2
HBr-H2SO4,3 NCS/NBS-Me2S,4 PBr3,5 oxalylchloride/DMF/CHCl3.6
(HCA-PPh3) complex7 and by the reaction of AlCl3/CH2Cl28 with the acet-
ate derived from the corresponding alcohol.
In continuation of our research programme.9 I herein report
a convenient synthesis of methyl(2Z)-2-(bromomethyl)alk-2-enoates by
treating methyl-3-hydroxy-2-methylenealkanoates with acetic anhydride
and magnesium bromide according to the following eq.1.
2059
Copyright & 2001 by Marcel Dekker, Inc.
www.dekker.com

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RAVICHANDRAN
Table 1. Synthesis of Methyl(2Z)-2-(bromomethyl)alk-2-enoatesa,b
Time
(minutes)
Yield
(%)c
Substrate
R
Product
Z:Ed
1a
1b
1c
1d
1e
1f
C6H5
60
60
60
60
70
90
90
2a12
2b
2c
2d
2e
86
83
81
81
80
68
71
100:0
100:0
96:04
100:0
95:05
94:06
95:05
4-MeC6H4
4-ClC6H4
4-1PrC6H4
4-MeC6H4
n-pentyl
2f
2g
1g
n-hexyl
aAll reaction were carried out in 2 mM scale of alcohol using acetic anhydride (4 mM)
and 6 mM scale of magnesium bromide in THF (5 ml) at room temperature.
bSatisfactory spectral data IR, 1H (200 MHz), and 13C NMR (50 MHz) were
obtained.
cIsolated yields after column chromatography (silica gel.1% ethyl acetate in hexane).
dStereochemical assignments and isomeric purities were based on defference in
1
chemical shifts and integration ratios of olefinic protons in H NMR analysis.
In a similar fashion, 3-hydroxy-2-methylenealkane-nitriles (3a–3g) on
reaction with acetic anhydride and magnesium bromide in THF at room
temperature for 1–1.5 hours afforded the desired regiomerically pure (2E )-
2-(bromomethyl)alk-2-enenitriles (4a–4g) in good yields with high (E)-selec-
tivity (eq.2) (Table 2).
From these results, it is clear that esters 1a–1g and nitriles 4a–4g
provide allyl bromides with opposite stereochemistry.This observation is
consistent with our earlier results10 and may be explained either to the

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(E)- AND (Z)-ALLYL BROMIDES
2061
Table 2. Synthesis of (2E)-2-(bromomethyl)alk-2-enenitrilesa,b
Time
(minutes)
Yield
(%)c
Substrate
R
Product
E:Zd
3a
3b
3c
3d
3e
3f
Phenyl
60
60
60
75
70
90
90
4a13
4b
4c
4d
4e
85
84
83
81
84
79
77
93:07
95:05
96:04
98:02
94:06
88:12
92:08
4-MeC6H4
4-ClC6H4
4-1PrC6H4
4-MeC6H4
n-pentyl
4f
4g
3g
n-hexyl
difference in steric demands between the nitrile and ester groups or to the
chelation effects.
In summary this study provides a simple stereoselective synthesis of
(Z)- and (E)-allyl bromides thus demonstrating the efficiency of magnesium
bromide, a very mild Lewis acid, as a stereoselective brominating reagent.
EXPERIMENTAL
All of the required Baylis-Hillman products were obtained by the
reaction of the corresponding aldehydes with methyacrylate/acrylonitrile
in the presence of a catalytic amount of DABCO according to the literature
procedure.11
General Procedure
To a solution of alcohol (1a–1g, 3a–3g) (2 mM) and acetic anhydride
(4 mM) were added to freshly prepared magnesium bromide (6 mM) in THF
(5 ml).The reaction mixture was stirred at room temperature for 1–1.5 h and
monitored by TLC.On completion of the reaction, solvent was removed
under reduced pressure and the residue purified by column chromatography
(silicagel, 1% EtOAc in hexane) to furnish the desired product (2a–2g,
4a–4g) in good yields.
ACKNOWLEDGMENTS
SR thanks his brothers SS and Dr. SP for financial support and
constant encouragement in research.

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RAVICHANDRAN
REFERENCES
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5. Semmelhack, M.F.; Wu, E.S.C. J. Am. Chem. Soc. 1976, 98, 3384.
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8. Basavaiah, D.; Pandiaraju, S.; Padmaja, K. Synlett. 1996, 4, 393.
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12.Spectral data for 2a: 1H NMR (200 MHz, CDCl3): d 3.85 (s, 3H), 4.36
(s, 2H), 7.33–7.57 (m, 5H), 7.84 (s, 1H); 13C NMR (50 MHz, CDCl3): d
26.62, 52.38, 128.60, 128.86, 129.55, 134.12, 143.11, 166.43; IR (neat):
1705, 1620 cmꢀ1
.
1
13.Spectral data for 4a: H NMR (200 MHz, CDCl3): d 4.19 (s, ꢀCH2
protons, (Z )-isomer), 4.23 (d, ꢀCH2 protons, J ¼ 0.8 Hz, (E)-isomer)
7.23 (s, vinylic proton, (E)-isomer), 7.34 (s, vinylic proton, (Z)-iso-
mer), 7.37–7.54 (m, 3H), 7.73–0.82 (m, 2H); 13C NMR (50 MHz,
CDCl3): d 26.63, 32.70, 108.06, 117.03, 129.04, 129.23, 130.44,
131.39, 132.41, 146.47, 147.21 in these the signals at 26.63, 130.44,
147.21 are due to minor (Z)-isomer: IR (KBr): 2120, 1610 cmꢀ1
.
Received in the Netherlands September 14, 2000

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