Montmorillonite clay-catalyzed stereoselective syntheses of aryl-substituted (E)- and (Z)-allyl iodides and bromides

Article abstract of DOI:10.1039/b103850h

An efficient and rapid procedure for the synthesis of allyl iodides and bromides from Baylis-Hillman adducts using clay-supported sodium iodide and sodium bromide is described. Improved yields and enhanced rates have been achieved by employing microwave i

Full text of DOI:10.1039/b103850h

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Montmorillonite clay-catalyzed stereoselective syntheses of
aryl-substituted (E)- and (Z)-allyl iodides and bromides
Jhillu S. Yadav,* Basi V. Subba Reddy and Chinnala Madan
Division of Organic Chemistry, Indian Institute of Chemical T echnology, Hyderabad-500 007
India. E-mail: yadav=iict.ap.nic.in; Fax: ]91-40-7170512
L e t t e r
Received (in Montpellier, France) 30th April 2001, Accepted 4th July 2001
First published as an Advance Article on the web 16th August 2001
An efficient and rapid procedure for the synthesis of allyl
iodides and bromides from Baylis–Hillman adducts using clay-
supported sodium iodide and sodium bromide is described.
Improved yields and enhanced rates have been achieved by
employing microwave irradiation.
leads to the formation of the corresponding (Z)-allyl iodides
and bromides in high yields (Table 1). However, the reaction
did not proceed in the absence of clay, even under microwave
irradiation. This clearly indicates the role of the catalyst for
the success of the reaction. These allyl bromides and iodides
are important precursors for the stereoselective synthesis of
allyl amines and azetidines.12 Furthermore, the reactions of
4-hydroxy-3-methylene alkan-2-ones with NaI and NaBr in
the presence of KSF clay gave the corresponding (Z)-allyl
iodides and bromides in high yields under microwave irradia-
tion. The Z stereochemistry of the products was assigned on
the basis of the chemical shift values of the vinyl and allylic
protons in the 1H NMR spectra of the products and also by a
comparison of the spectral data with authentic compounds. In
the 13C NMR spectra of trisubstituted oleÐns, an allylic
carbon cis to the aryl group appears upÐeld while the same
carbon trans to the aryl group appears downÐeld.13
The reactions proceeded smoothly under microwave irra-
diation and produced high yields of products. The reactions
are very clean and highly stereoselective. The reaction rates
and yields are dramatically enhanced by microwave irradia-
tion. The rate enhancement under microwave irradiation may
be attributed to the absorption of more microwave energy by
the polar media, which generates heat energy as required to
promote the reaction. The irradiation was carried out at 450
W using a BPL, BMO-700T domestic microwave oven. The
reaction temperature reached 110 ¡C after 3 min pulsed irra-
diation (1 min on with 20 s o† interval) at constant power.
The same reaction, under thermal conditions, at 110 ¡C took
5È8 h to a†ord yields comparable with those that are obtained
by microwave irradiation.
The coupling of activated vinyl moieties with aldehydes in the
presence of 1,4-diazabicyclo[2,2,2]octane (DABCO), known as
the BaylisÈHillman reaction, is widely used for the direct syn-
thesis of a-hydroxy alkyl- or arylvinyl systems.1 The BaylisÈ
Hillman adducts are very useful precursors for the synthesis of
a variety of biologically active natural products.2 In particu-
lar, 2-(halomethyl)alk-2-enolates are an important class of
compounds for the stereoselective synthesis of many natural
products3 such as a-alkylidene-b-lactams, a-methylene-c-buty-
rolactones and necic acids. As a result, several methods have
been developed for the direct conversion of 3-hydroxy-2-
methylene alkanoates to 2-(halomethyl)alk-2-enoates, includ-
ing those using HBrÈH SO ,3b NBSÈMe S,2c PBr ,4
2
4
2
3
MsClÈEt N5 and CuBr Èsilica gel.6 Recently, the synthesis of
3
2
2-(halomethyl)alk-2-enoates has been reported from the acetyl
derivative of BaylisÈHillman adducts7 using MgBr ÈTHF and
2
AlCl ÈCH Cl . However, there is no report of the synthesis of
allyl iodides from BaylisÈHillman adducts.
3
2 2
The use of corrosive and/or hazardous reagents and
harmful organic solvents is undesirable in view of todayÏs
environmental consciousness. There is much to be gained in
developing simple and convenient procedures using inexpen-
sive solid acids8 such as clays, zeolites and ion-exchange
resins. In particular, clays are most attractive9 because of their
reusability, environmental compatibility, low cost, non-
toxicity, and operational/experimental simplicity. In continua-
tion of our interest in the applications of clays10 for various
transformations, we report here the remarkable catalytic
activity of a montmorillonite clay for the synthesis of 2-(iodo
or bromomethyl)aryl-2-enoates from 3-hydroxy-2-methylene
alkanoates (Scheme 1). In addition, microwave irradiation,
which has become a powerful tool11 for the rapid synthesis of
a variety of organic compounds, is used to enhance the rates
of reaction.
The reactions of BaylisÈHillman adducts derived from
acrylonitrile, that is 3-hydroxy-2-methylene alkanenitriles with
NaI and NaBr in the presence of KSF clay, produced the cor-
responding (E)- and (Z)-allyl iodides and bromides in high
yields (Scheme 2). Under these conditions, the products were
obtained as a mixture of E and Z isomers. The ratio of the
isomers was determined from the integration ratios of the
isomeric oleÐnic and allylic methylene protons in the 1H
NMR spectra of the products. The E stereochemistry of the
major isomer was assigned by comparing the chemical shift
values of allylic methylene and vinyl protons with those of
authentic compounds.13 Several examples illustrating this
The treatment of BaylisÈHillman adducts derived from
acrylate esters such as 3-hydroxy-2-methylene alkanoates with
clay-supported NaI and NaBr under microwave irradiation
Scheme 1
Scheme 2
1114
New J. Chem., 2001, 25, 1114È1117
DOI: 10.1039/b103850h
This journal is ( The Royal Society of Chemistry and the Centre National de la Recherche ScientiÐque 2001

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Table 1 Microwave-assisted synthesis of allyl iodides and bromides
Reaction time (yield (%))
Irradiationa/min
4 (87)
Entry
Substrate
Nucleophile
NaBr
Conventionalb/h
E : Zc
a
6 (73)
0 : 100
b
c
NaI
NaI
3 (89)
3 (80)
5 (81)
7 (74)
0 : 100
0 : 100
d
e
NaBr
NaI
5 (78)
4 (85)
8 (65)
7 (70)
0 : 100
0 : 100
f
NaBr
NaI
5 (81)
4 (90)
8 (63)
6 (77)
0 : 100
0 : 100
g
h
i
NaBr
NaI
5 (84)
4 (87)
8 (75)
6 (80)
0 : 100
0 : 100
j
NaI
3 (85)
5 (78)
87 : 13
k
l
NaBr
NaI
4 (78)
3 (83)
6 (65)
5 (71)
89 : 11
91 : 09
m
n
NaBr
NaI
4 (80)
3 (88)
7 (68)
5 (70)
93 : 07
95 : 05
a Pulsed irradiation (1 min with 20 s interval). b Conventional heating at 110 ¡C. c E : Z ratio was based on integration ratios of isomeric allylic
and vinylic protons in 1H NMR spectra.
novel and rapid procedure for the synthesis of (Z)- and (E)-
allyl iodides and bromides are listed in Table 1.
method over protic and Lewis acid-catalyzed procedures. The
recovered clay could also be activated by microwave irradia-
tion at 450 W for 10È15 min.
In summary we have demonstrated a rapid and highly effi-
cent procedure for the synthesis of (Z)- and (E)-allyl iodides
and bromides using clay-supported NaI and NaBr. The
method o†ers several advantages including mild reaction con-
ditions, enhanced rates, improved yields, greater selectivity,
experimental simplicity and reusability of the catalyst, which
After completion of the reaction, the clay was recovered by
Ðltration, washed with methanol and reused in subsequent
reactions (after activation at 120 ¡C for 4È5 h) with a gradual
decrease in activity; for example, the reaction of methyl 2-
hydroxy(phenyl)methyl acrylate (entry b) and NaI under
microwave radiation gave 89, 77 and 75% yields over three
cycles. These results clearly show the advantage of our
New J. Chem., 2001, 25, 1114È1117
1115

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makes it a convenient, more economical and environmentally
benign process.
2i. Viscous liquid: 1H NMR (CDCl ) d: 2.45 (s, 3H), 4.20 (s,
3
2H), 7.20 (s, 1H, Z isomer), 7.30 (d, 2H, J \ 7.8. Hz), 7.70 (d,
2H, J \ 7.8 Hz). EI-MS m/z: 320 M`, 193, 178, 150, 115, 75,
63.
Experimental
Conventional method
3j. Semi-solid: 1H NMR (200 MHz, CDCl ) d: 4.19 (s, 2H,
3
Z isomer, ÈCH È), 4.21 (s, 2H, E isomer ÈCH È), 7.19 (s, 1H, E
A mixture of the BaylisÈHillman adduct (5 mmol), NaI or
NaBr (6 mmol) and KSF clay (1 g, Aldrich Co.) was heated at
110 ¡C for the time speciÐed in the table. After complete con-
version, as indicated by TLC, the reaction mixture was Ðltered
and washed with dichloromethane (2 ] 15 mL). The solvent
was removed in vacuo and the residue puriÐed by column
chromatography (Merck, 100È200 mesh, ethyl acetateÈhexane
5 : 95) to a†ord pure product.
2
2
isomer ÈCH2C), 7.22 (s, 1H, Z isomer ÈCH2C), 7.45È7.55 (m,
3H), 7.75È7.85 (m, 2H). 13C NMR (CDCl , proton decoupled)
3
d: 28.81, 38.69, 109.62, 116.9, 128.35, 128.86, 129.0, 129.7,
129.93, 130.64, 130.92, 132.54, 144.38, 144.71.
3k. Liquid: 1H NMR (200 MHz, CDCl ) d: 4.18 (s, 2H, Z
3
isomer ÈCH È), 4.20 (s, 2H, E isomer ÈCH È), 7.18 (s, 1H, E
2
2
isomer ÈCH2C), 7.28 (s, 2H, Z isomer ÈCH2C), 7.40È7.55 (m,
3H), 7.75È7.85 (m, 2H). 13C NMR (CDCl , proton decoupled)
Under microwave irradiation
3
d: 26.67, 32.75, 108.06, 117.07, 129.10, 129.23, 130.45, 131.38,
The BaylisÈHillman adduct (5 mmol), NaI or NaBr (6 mmol)
and KSF clay (1 g, Aldrich Co.) were admixed in a Pyrex test
tube and subjected to microwave irradiation at 450 W using a
BPL, BMO-700T microwave oven for 3È5 min. After com-
plete conversion, as indicated by TLC, the reaction mixture
was Ðltered and washed with dichloromethane (2 ] 15 mL).
The solvent was removed in vacuo and the residue puriÐed by
column chromatography (Merck, 100È200 mesh, ethyl
acetateÈhexane 5 : 95) to a†ord pure product.
132.40, 146.50, 147.18. IR (KBr) l/cm~1: 2960, 2125, 1620,
1580.
3l. Liquid: 1H NMR (CDCl ) d: 4.09 (s, 2H, Z isomer
3
ÈCH È), 4.15 (s, 2H, E isomer ÈCH È), 7.05 (s, 1H, E isomer
2
2
ÈCH2C), 7.20 (s, 1H, Z isomer ÈCH2C), 7.50 (d, 1H, J \ 8.0
Hz), 7.70 (dd, 1H, J \ 8.0 and 2.0 Hz), 7.80 (d, 1H, J \ 2.0
Hz). EI-MS m/z: 337 M`, 210, 177, 140, 127, 113, 87, 75, 63,
50.
2a. Liquid: 1H NMR (CDCl ) d: 3.90 (s, 3H), 4.35 (s, 2H),
3
3m. Liquid: 1H NMR (CDCl ) d: 4.15 (s, 2H, Z isomer
7.45 (m, 3H), 7.55 (m, 2H), 7.85 (s, 1H). 13C NMR (CDCl ,
3
3
ÈCH È), 4.18 (s, 2H, E isomer ÈCH È), 7.10 (s, 1H, E isomer
proton decoupled) d: 26.7, 52.35, 128.70, 128.85, 129.60,
2
2
ÈCH2C), 7.20 (s, 1H, Z isomer ÈCH2C), 7.55 (d, 1H, J \ 8.0
Hz), 7.75 (dd, 1H, J \ 8.0 and 2.0 Hz), 7.80 (d, 1H, J \ 2.0
Hz). EI-MS m/z: 289 M`, 210, 175, 140, 88. IR (KBr) l/cm~1:
3060, 2360.7, 1623.4, 1449, 1215.3, 1078.9, 755.7, 690.8.
134.27, 142.78, 166.38. IR (KBr) l/cm~1: 1714.2, 1632.8,
1587.9, 1469.9, 1135.6, 1068.2, 765.
2b. Solid, m.p. 50È52 ¡C: 1H NMR (CDCl ) d: 3.90 (s, 3H),
3
4.30 (s, 2H), 7.45È7.65 (m, 6H). 13C NMR (CDCl , proton
3
decoupled) d: 25.18, 25.90, 129.6, 129.7, 129.8, 134.35, 137.45,
3n. Semi-solid: 1H NMR (CDCl ) d: 4.15 (s, 2H, Z isomer
3
142.70, 197.05. EI-MS m/z: 238 M`, 158, 143, 115, 77, 57. IR
(KBr) l/cm~1: 2950, 1617, 1625.
ÈCH È), 4.20 (s, 2H, E isomer ÈCH È), 7.10È7.25 (m, 5H),
2
2
7.35È7.50 (m, 4H), 7.60 (d, 1H, J \ 7.8 Hz). 13C NMR
(CDCl , proton decoupled) d: 27.60, 35.80, 110.5, 118.1, 118.7,
3
2c. Liquid: 1H NMR (CDCl ) d: 3.90 (s, 3H), 4.28 (s, 2H),
119.2, 119.5, 119.8, 121.0, 123.25, 123.87, 124.19, 129.87, 130.02,
3
7.70 (t, 1H, J \ 7.8 Hz), 7.75 (s, 1H, Z isomer), 7.90 (d, 1H,
130.46, 134.22, 143.74, 144.09, 157.89. FAB-MS m/z: 354 M`,
329, 307, 244, 212, 186, 172, 156, 129, 115, 105, 81, 69, 57. IR
(KBr) l/cm~1: 2354.4, 1695.8, 1541.8.
J \ 8 Hz), 8.28 (d, 1H, J \ 8 Hz), 8.40 (s, 1H). EI-MS m/z:
347 M`, 316, 220, 174, 150, 128,115, 89, 59. IR (KBr) l/cm~1:
1742.5, 1667, 1624, 1465, 1026.8, 816.5, 668.7.
2d. Solid, m.p. 125 ¡C: 1H NMR (CDCl ) d: 3.90 (s, 3H),
Acknowledgement
B. V. S. R. thanks CSIR (New Delhi) for the award of a fellow-
ship.
3
4.30 (s, 2H), 7.65 (d, 2H, J \ 8.4 Hz), 7.80 (s, 1H), 8.20 (d, 2H,
J \ 8.4 Hz). IR (KBr) l/cm~1: 2960, 1725, 1630, 1520.
2e. Viscous liquid: 1H NMR (CDCl ) d: 3.90 (s, 3H), 4.28
3
(s, 2H), 7.40 (dd, 1H, J \ 7.8 and 2.0 Hz), 7.60 (s, 1H, Z
isomer), 7.65 (d, 1H, J \ 7.8 Hz), 7.68 (d, 1H, J \ 2.0 Hz).
EI-MS m/z: 370 M`, 243, 213, 183, 150, 128, 113, 74, 59. IR
(KBr) l/cm~1: 1713.2, 1631.9, 1550.5, 1469.9, 1283.5, 1068.2,
822.7.
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2f. Semi-solid: 1H NMR (CDCl ) d: 3.90 (s, 3H), 4.30 (s,
3
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1116
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