Catalytic Hunsdiecker reaction and one-pot catalytic Hunsdiecker-Heck strategy: Synthesis of α,β-unsaturated aromatic halides, α- (dihalomethyl)benzenemethanols, 5-aryl-2,4-pentadienoic acids, dienoates and dienamides

Article abstract of DOI:10.1016/S0040-4020(99)01035-2

The reaction of α,β-unsaturated aromatic (or heteroaromatic) carboxylic acids with N-halosuccinimides (1 equiv.) and catalytic tetrabutylammonium trifluoroacetate (0.2 equiv.) in dichloroethane results in facile halodecarboxylation affording the corresponding (E)-halides in good to excellent yields. A similar reaction, but with 2 equiv. of N-halosuccinimides in acetonitrile-water (1:1 v/v) results in the exclusive formation of the corresponding α-(dihalomethyl)benzenemethanols. Furthermore, a one-pot strategy has been developed combining catalytic Hunsdiecker reaction (using tetrabutylammonium trifluoroacetate in dichloroethane) and Heck coupling (using palladium acetate/triethylamine/triphenylantimony/dichloroethane) for the synthesis of 5-aryl-2,4-pentadienoic acids, esters and amides in moderate to good yields. The natural product piperine and pipergualamine has been synthesized via the above route. Mechanistic and theoretical studies (via AM1 calculations) provide a useful insight into the mechanism of the present halodecarboxylation reaction, suggesting an ionic pathway involving the attack of the halogenium ion across the carbon-carbon double bond, triggering the elimination of carbon dioxide. (C) 2000 Elsevier Science Ltd.

Full text of DOI:10.1016/S0040-4020(99)01035-2

TETRAHEDRON
Pergamon
Tetrahedron 56 (2000) 1369–1377
Catalytic Hunsdiecker Reaction and One-Pot Catalytic
Hunsdiecker–Heck Strategy: Synthesis of a,b-Unsaturated
Aromatic Halides, a-(Dihalomethyl)benzenemethanols,
5-Aryl-2,4-pentadienoic acids, Dienoates and Dienamidesଝ
*
Dinabandhu Naskar and Sujit Roy
Metallo-Organic Laboratory, Inorganic Division, Indian Institute of Chemical Technology, Hyderabad 500007, India
Received 16 June 1999; revised 11 November 1999; accepted 25 November 1999
Abstract—The reaction of a,b-unsaturated aromatic (or heteroaromatic) carboxylic acids with N-halosuccinimides (1 equiv.) and catalytic
tetrabutylammonium trifluoroacetate (0.2 equiv.) in dichloroethane results in facile halodecarboxylation affording the corresponding
(E)-halides in good to excellent yields. A similar reaction, but with 2 equiv. of N-halosuccinimides in acetonitrile-water (1:1 v/v) results
in the exclusive formation of the corresponding a-(dihalomethyl)benzenemethanols. Furthermore, a one-pot strategy has been developed
combining catalytic Hunsdiecker reaction (using tetrabutylammonium trifluoroacetate in dichloroethane) and Heck coupling (using
palladium acetate/triethylamine/triphenylantimony/dichloroethane) for the synthesis of 5-aryl-2,4-pentadienoic acids, esters and amides
in moderate to good yields. The natural product piperine and pipergualamine has been synthesized via the above route. Mechanistic and
theoretical studies (via AM1 calculations) provide a useful insight into the mechanism of the present halodecarboxylation reaction,
suggesting an ionic pathway involving the attack of the halogenium ion across the carbon–carbon double bond, triggering the elimination
of carbon dioxide. ᭧ 2000 Elsevier Science Ltd. All rights reserved.
Introduction
We have recently invoked a novel protocol whereby a
catalytic metal–salt pool is utilized in mediating a one-pot
Hunsdiecker synthesis from in-situ generated metal carboxy-
lates.4 The major question that warranted further investi-
gation is: ‘What triggers the elimination of carbon
dioxide?’ In the classical Hunsdiecker reaction, the
elimination of carbon dioxide is believed to originate from
hard–soft interaction between carboxylate oxygen as hard
base and metal such as Ag, Tl, Hg, and Pb as soft acid. Such
an interaction leads to homolytic cleavage of the M–O
bond, thereby dictating the decarboxylation via a free-radi-
cal pathway. In the present study the interaction between
carboxylate oxygen and group-1 metal ion is primarily a
hard–hard interaction, leading to dominant ionic character.
Therefore, it is necessary to find out whether the carboxylate
anion of the a,b-unsaturated carboxylic acid is greatly
involved in the catalytic Hunsdiecker reaction (CHR). In
this direction, generating the carboxylate anion from the
reaction of acid with an ‘all-organic’ catalyst appeared to
be an interesting exercise. We delineate herein a study in
this direction and our effort in coupling the halodecarboxy-
lation reaction with the Heck reaction in one-pot. Both the
strategies resulted in new routes to synthetically important
intermediates namely a,b-unsaturated aromatic halides,
a-(dihalomethyl)benzenemethanols, 5-aryl-2,4-pentadienoic
acids, dienoates and dienamides.
The halodecarboxylation of Ag(I), Hg(II), Tl(I) or Pb(IV)
carboxylates with molecular halogen, trivially known as the
Hunsdiecker reaction, is of proven utility for the synthesis of
various organic halides notably alkyl (1Њ, 2Њ, 3Њ) and aryl
halides.1 When we viewed this classical reaction from a
synthetic organic chemists perspective, the necessity to
use stoichiometric metal carboxylate appeared against the
dictum of atom-economy.2 Other limitations include: (a) the
necessity to use high temperature; (b) the toxicity/hazard
related to molecular bromine and salts of Hg, Tl, Pb, Ag;
and (c) very poor yields3 in cases of substrates such as
a,b-unsaturated carboxylic acids.
ଝ
Presented in part at the Indo-German Symposium on Organic Synth-
esis—Growing Interface with Adjacent Sciences, Hyderabad, India,
September 27–28, 1996; National Symposium on Frontier Areas in Organic
Chemistry, Pune, India, February 14–15, 1997; and National Symposium in
Chemistry, Bangalore, India, January 27–30, 1999. This is IICT commu-
nication no. 4257.
Keywords: catalytic Hunsdiecker reaction; Heck coupling; unsaturated
aromatic halides.
* Corresponding author. Address for correspondence: Organometallics &
Catalysis Laboratory, Chemistry Department, Indian Institute of Tech-
nology, Kharagpur 721302, India; e-mail: royiitkgp@hotmail.com
0040–4020/00/$ - see front matter ᭧ 2000 Elsevier Science Ltd. All rights reserved.
PII: S0040-4020(99)01035-2

1370
D. Naskar, S. Roy / Tetrahedron 56 (2000) 1369–1377
Table 1. Optimization parameters in CHR of cinnamic acid 1 to b-bromo-
styrene 1a
Table 2. CHR of a,b-unsaturated acids to haloalkenes (unless otherwise
stated, the isomeric purity of the E acids and corresponding (E)-haloalkenes
is Ͼ97% (vide H NMR))
1
Acid
No.
X
Pdt.
no.
Time
(h)
Yield
(%)a
Br
Cl
I
1a
1b
1c
6
16
20
73
1
78
#
Solvent
Catalyst
Yield (%)a
18b
a
b
c
d
e
f
g
h
i
MeCN–H2O
Bu4NϩOAcϪ
29
47
20
20
30
15
31
34
45
15
48
73
Bu4NOC(O)CF3
Br
Cl
I
2a
2b
2c
2
6
4
94
87
74
Bu4NϩOHϪ
2
3
PhCH2NϩMe3OAcϪ
PhCH2NϩMe3ϪOC(O)CF3
PhCH2NϩMe3OHϪ
Bu4NOC(O)CF3
Bu4NOC(O)CF3
Bu4NOC(O)CF3
Bu4NOC(O)CF3
Bu4NOC(O)CF3
Bu4NOC(O)CF3
CH2Cl2
CHCl3
MeCN
CH3NO2
Cl2CHCHCl2
ClCH2CH2Cl
Br
Cl
I
3a
3b
3c
4
7
4
96
93c
73d
j
k
l
4
5
Br
Br
4a
5a
5
4
90
a Reaction time: 16 h (entries a–f); 6 h (entries g–l). Isolated yield with
respect to acid.
93e
6
Br
6a
27
51
Results and Discussion
CHR of cinnamic acid with tetraalkylammonium salts as
catalyst
7
8
Br
Br
7a
8a
13
18
21
91
Initial attempts to react cinnamic acid 1 (1 mmol), with NBS
(1.12 mmol), tetrabutylammonium acetate (0.2 mmol) in
acetonitrile–water (97:3 v/v) at ambient temperature gave
rise to b-bromostyrene in 29% yield (Table 1, entry a).
Several variations in the counter cation and anion in the
catalyst were made in an attempt to improve the yield of
the b-bromostyrene 1a (entries b–f). Tetrabutylammonium
trifluoroacetate (TBATFA) was found to be the best catalyst
yielding 1a in 47% yield (entry b). The influence of
trifluoroacetate in the classical Hunsdiecker reaction is
well documented.5 We next looked into the effect of
solvents in CHR. To our gratification, dichloroethane
(DCE) promotes the halodecarboxylation in remarkable
fashion.6 Thus reaction of cinnamic acid (8 mM) with
NBS (11.5 mM) and tetrabutylammonium trifluoroacetate
(TBATFA) (1.6 mM) in DCE (16 mL) at ambient tempera-
ture after 6 h furnishes b-bromostyrene in 73% isolated
yield (entry 1).
9
Br
Cl
I
9a
9b
9c
8
30
64
97
88
73
10
Br
Cl
10a
10b
21
70
71
68
11
12
I
11a
12a
0.5
27
63
Br
Ͻ15
a Isolated yields with respect to acid.
b Rapid decomposition during chromatography.
c E:Zˆ1:1.
d E:Zˆ89:11.
Analogous chlorodecarboxylation using NCS affords
b-chlorostyrene 1b in 78% isolated yield (Table 2).
Although iododecarboxylation proceeds with equal ease
(vide NMR), the product is isolated in low yield due to
rapid decomposition during chromatography. It is note-
worthy that the present strategy brings the Hunsdiecker
synthesis from stoichiometric metal carboxylate protocol
to catalytic metal-free version.7
e Acid E:Zˆ87:13; halide E:Zˆ75:25.
CHR of a,b-unsaturated carboxylic acids with
tetrabutylammonium trifluoroacetate as catalyst
Encouraged by studies with cinnamic acid, the metal-free

D. Naskar, S. Roy / Tetrahedron 56 (2000) 1369–1377
1371
Table 3. Conversion of a,b-unsaturated acids to a-(dibromomethyl)ben-
zenemethanol
catalytic Hunsdiecker reaction was extended to various
substituted cinnamic acids 2–7 (Table 2). For example,
reaction of 4-methoxycinnamic acid 2 with NBS, TBATFA
(0.2 mmol) in DCE (3 mmol) at ambient temperature
affords 4-methoxy-b-bromostyrene 2a in 94% isolated
yield. Similar reactions with NCS, NIS furnishes 2b, 2c,
in 87, 74% isolated yield, respectively. Reduced reaction
time and higher yields of products are noteworthy for
acids 2–5 bearing electron donating substituents either in
the aromatic ring or alkene appendage as compared to acids
6 and 7 having electron withdrawing substituents. A futher
salient feature of these reactions is the moderate to good
degree of stereospecificity, wherein (E)-acids give rise to
corresponding (E)-1-bromoalkenes as the major product.
#
a
Acid
no.
Product
No.
Yield
(%)a
1
13
68
b
c
d
e
f
2
14
15
16
17
18
80
To further investigate the generality of our protocol, various
precursors containing unsaturated carboxylic appendages
are chosen. Dienoic acid 8 affords the corresponding bro-
mide 8a in 91% yield. Piperonal derivative 9, 9-anthracenyl
acrylic acid 10 and 2-thienyl acrylic acid 11 undergo very
facile halodecarboxylation giving rise to the corresponding
halides 9a–9c, 10a and 10b, and 11a, respectively, as the
exclusive E-isomer. On the other hand, furylacrylic acid 12
gives rise to the desired Hunsdiecker product 12a in low
yield. Compound 12a is unstable in solution and
characterized by NMR only.
2
2
3
4
73
60
90
78
CHR in organic–aqueous phase—a facile route to
a-(dihalomethyl)benzenemethanol
A particularly interesting aspect in the present halo-
decarboxylation reaction is the remarkable role of solvents.
Switching from dichloroethane to acetonitrile–water results
in the concomitant formation of a-(dibromomethyl)benzene-
methanol (Table 3). Thus the reaction of cinnamic acid 1
(1 mmol) with NBS (1.05 mmol), TBATFA (0.2 mmol) in
acetonitrile–water (80:20) results in the formation of
Table 4. Optimization parameters in one-pot catalytic Hunsdiecker–Heck
(CHH) reaction
g
h
9
19
20
79
63
b
((a) NBS/TBAFTA; (b) CH2vCH–CO2Me/Pd(OAc)2/LiCl/Et3/N/L)
#
Solvent
Heck ligand (L)
Yield (%)a
i
j
6
7
21
22
51
30
23
4a
a
b
c
d
e
f
g
h
i
MeCN–H2O
MeCN–H2O
MeCN–H2O
MeCN
DCE
MeCN
DCE
MeCN
DCE
MeCN
–
PPh3
Ph3Sb
PPh3
–
10
49
6
15
30
35
10
30
55
83
90
80
40
75
62
58
60
73
55
20
Ͻ5
PPh3
(p-Tolyl)3P
(p-Tolyl)3P
(p-Tolyl)3As
(p-Tolyl)3As
Ph3Sb
j
k
a Reaction time 16 h in all cases. Isolated yield with respect to acid.
b 1-Naphthylacrylic acid.
DCE
Ph3Sb
a Isolated yield with respect to acid.

1372
D. Naskar, S. Roy / Tetrahedron 56 (2000) 1369–1377
Table 5. One-pot catalytic Hunsdiecker–Heck reaction
#
a
Acid no.
EWG
Product
No.
Yield (%)a
81
4
–CO2Et
24
b
c
d
e
2
2
3
4
–CO2Me
–CO2H
25
26
27
28
45
50
52
47
–CO2Me
–CONH2
–CO2H
f
11
9
29
30
42
51
g
h
9
–CONHCH2CHMe2
31
34
a Isolated yield with respect to acid.
b-bromostyrene 1a and a-(dibromomethyl)benzenemetha-
nol 13 along with unreacted acid in 32, 24 and 25% isolated
yields, respectively, after column chromatography. Upon
increasing the concentration of water and the concentration
of NBS in steps, a simultaneous increase in the yield of 13
is noticed. a-(Dibromomethyl)benzenemethanol 13 is
obtained as the exclusive product (vide TLC) when
2 equiv. of NBS and acetonitrile–water (1:1 v/v) is used,
the isolated yield being 68% (entry a).
(0.2 equiv.). The reaction has been further extended to
various unsaturated acids (Table 3, entries b, e–j). Barring
6 and 7, all the acids afford the corresponding a-(dibromo-
methyl)benzenemethanols 14–20 in excellent yields. The
reaction proceeds with equal ease with N-chloro and
N-iodo succinimides as well (entries c and d).
One-pot catalytic Hunsdiecker–Heck (CHH) strategy
for the synthesis of 5-aryl-2,4-penta dienoic acids,
dienoates and dienamides
The intermediacy of b-bromostyrene towards the formation
of a-(dibromomethyl)benzenemethanol has been confirmed
in control experiments with 1, NBS (1 equiv.) and TBATFA
5-Aryl-2,4-pentadienoic acids and their derivatives exhibit a
wide array of biological activities.8 The (2E,4E)-dienamides

D. Naskar, S. Roy / Tetrahedron 56 (2000) 1369–1377
1373
Scheme 1. A plausible mechanism of CHR.
derived from piperidine, pyrrolidine and isobutylamine
belong to an important class of alkaloids which are common
flavour constituents and also show both physiological and
insecticidal activities.9 Beside the traditional routes10 like
condensation, Reformatsky reaction and Wittig coupling,
several new routes11 have accrued in literature for their
synthesis. Enthused by our new-found catalytic
Hunsdiecker tool for the conversion of a,b-unsaturated
carboxylic acids to the corresponding vinyl halides, we
aimed in devising a one-pot strategy for the synthesis of
5-aryl-2,4-pentadienoic acids and derivatives using a halo-
decarboxylation/C–C coupling protocol. (Tables 4 and 5).
We believe that such a protocol will provide an easy access
to library synthesis of the title compounds.
Mechanism of CHR
Since no significant change in reaction time and yield of
b-bromostyrene is observed for the reaction of cinnamic
acid with NBS/TBATFA, in presence of N-a-diphenyl
nitrone as radical trap, we believe that an ionic pathway is
1
most likely. Unfortunately, from in-situ H NMR moni-
toring at low temperature, no intermediate signal is
detected. Our quest for the intermediate in CHR prompted
us next to semi-empirical calculations. AM1 calculations
were carried out mainly to look into the geometry around
pCvC in various plausible intermediate species. For sim-
plicity in calculation, ammonium ion was chosen instead
of tetraalkyl ammonium ion. As described below, such
calculations provide useful mechanistic insight suggesting
attack of the bromonium ion at the pCvC, triggering the
elimination of carbon dioxide (Scheme 1).
Since a one-pot strategy needs to be adaptive to two different
reaction conditions, optimization of various parameters is
warranted. It is further noteworthy that Heck coupling of
b-halostyrenes with acrylic acid and derivatives was not
investigated in detail by earlier workers.12 In view of the
above, the Hunsdiecker–Heck route was initially explored
under varying conditions for the synthesis of the methyl
ester of 5-(4-methylphenyl)-2,4-pentadienoic acid 23
starting from 4-methylcinnamic acid 4. The results,
summarized in Table 4, indicate that changes in solvent
and Heck-ligand (L) markedly influence the yield of 23. A
combination of dichloroethane, TBATFA and triphenyl-
antimony is adjudged as best. Under this condition, 23 is
isolated in 83% yield and as an all-E isomer (entry k).
That the carboxylate anion halodecarboxylates faster than
the acid itself, is evidenced by the pronounced catalytic
effect of tetraalkylammonium salts. Since experiments are
conducted in organic solvent, we believe that the anion is
held as tight-ion pair with tetraalkylammonium ion (II in
Scheme 1). The HOMO of II, at an energy of Ϫ9.43 eV,
shows higher orbital amplitude at the alkene a-carbon
(bound to carboxylate), compared to the b-carbon (bound
to phenyl ring). The LUMO, at Ϫ0.70 eV, is primarily
located at the aromatic residue. Interestingly, the charge at
the a-carbon is Ϫ0.202 compared to a charge of Ϫ0.026 at
the b-carbon. This suggests the regioselective attack of the
bromonium ion at the a-carbon in II (Fig. 1). The argument
gains further support from the optimized structure of III
As a further test of the synthetic adaptability of the present
methodology, we have synthesized various 2,4-pentadienoic
acids and derivatives 24–29, bearing 5-aryl and heteroaryl
substituents, in moderate to excellent yields (Table 5). It is
noteworthy that all the compounds show Ͼ95% stereo-
selectivity towards the (2E,4E)-isomer. Application of our
one-pot protocol is further demonstrated in the one-pot
synthesis of natural products piperine13 30 and pipergual-
amine14 31 (entries g and h). The Heck precursors 1-acryl-
oxypiperidine and 1-acryloxy isobutylamine were
synthesized by modification of literature method.15 To our
knowledge, this is shortest route for these important natural
products reported so far.
˚
(Fig. 2) where the Ca–Br bond (1.95 A, close to a Br–Csp3
bond) is significantly shorter than the Cb–Br bond (2.74 A).
A weakening of the Ca–COO bond in III (1.51 A)
compared to that in II (1.46 A) indicates the elimination
˚
˚
˚
of carbon dioxide.
Conclusion
The synthesis of vinyl halides in a stereo-defined fashion
continues to be a challenging synthetic task, many new
Figure 1. AM1 derived optimized structure of II.
Figure 2. AM1 derived optimized structure of III.

1374
D. Naskar, S. Roy / Tetrahedron 56 (2000) 1369–1377
routes being accrued in the recent literature. The metal-free
catalytic Hunsdiecker reaction described in the present
study is a potentially attractive synthetic methodology for
the construction of (E)-vinyl halides having aromatic and
heteroaromatic appendage. The reaction has been scaled up
by us in several cases without sacrificing the product yields.
The present synthesis of a-(dihalomethyl)benzenemetha-
nols must be viewed with respect to earlier procedures
which require stringent low temperature Grignard method-
ologies. The novel one-pot Hunsdiecker–Heck strategy in
constructing aryl substituted (2E,4E)-dienoic acids, esters
and amides provides yet another synthetically amenable
route to these potentially useful precursors. Finally, the
success of the CHR and CHH stratagem puts forth the
Hunsdiecker reaction into yet another frontier that consists
of atom economy, mild reaction conditions and reduced
environmental hazard thereby enhancing its industrial merit.
monitored by TLC (eluent 20% ethyl acetate/hexane).
After completion of the reaction, solvent was removed
under reduced pressure and the residue was treated with
NaCl and extracted with ethyl acetate. The organic layer
was dried over anhydrous MgSO4 and the crude mixture
was subjected to column chromatography (silica gel, eluent
5% ethyl acetate/hexane) to afford a-(dihalomethyl)benzene-
methanol 13–22.
General procedure of one-pot catalytic Hunsdiecker–
Heck strategy for the synthesis of 5-aryl-2,4-penta-
dienoic acids, dienoates and dienamide, piperine,
pipergualamine
NBS (1.5 mmol) was added in portions to a mixture of acid
(1 mmol) and TBATFA (0.2 mmol) in 3 mL DCE. After
stirring for 4 h at ambient temperature, LiCl (3 mmol),
Et3N (3 mmol), Pd(OAc)2 (0.05 mmol) and Ph3Sb
(0.15 mmol), were added sequentially under nitrogen.
After stirring for 10 min at ambient temperature, Heck
precursor (3 mmol) was added and the mixture was heated
at 90ЊC (bath temperature) for 20 h under nitrogen. After
solvent removal, the mixture was extracted with ether,
washed with water and brine. The organic part was dried
over anhydrous MgSO4. After evaporation of solvent, the
mixture was subjected to column chromatography (silica
gel, eluent 5% ethyl acetate/hexane) to afford the desired
product.
Experimental
General experimental procedures are as described
previously.16 N-Bromosuccinimide, N-Chlorosuccinimide
(Loba) were recrystallized from water prior to use. N-Iodo-
succinimide (Lancaster) was used as received. Dichloro-
ethane was distilled from phosphorus pentoxide.
Acetonitrile (analytical grade) was distilled before use.
Substituted aromatic unsaturated carboxylic acids were
synthesized from the corresponding aldehydes (Lancaster,
Ranbaxy).
Procedure for synthesis of 1-acryloxy piperidine and
1-acryloxy isobutylamine
Semi-empirical calculations (AM1) were performed using
the program Hyperchem᭨ 5.0 (Hypercube Inc., Ontario,
Canada). The spin pairing mode and electronic state were
set to RHF and lowest respectively. During geometry
optimization, the convergence limit was set to 0.01 kcal/
mol. The algorithm and RMS gradient were Polak–Ribiere
(conjugate gradient) and 0.01 kcal/(A mol), respectively.
The convergence limit was changed to 0.0001 kcal/mol
for the calculation of orbital energy diagram.
A mixture of hydroquinone (5 mg), dry triethylamine
(9 mmol) and dry piperidine or dry isobutylamine
(5 mmol) in 2 mL dry benzene was placed in a 50 mL
two-necked flask equipped with addition funnel and CaCl2
guard tube. Then acrylyl chloride (5 mmol) in 2 mL dry
benzene was added to the reaction mixture dropwise at
cold condition. It was allowed to stir for 5 h at ambient
temperature. It was filtered over celite and concentrated
under reduced pressure and the mixture was subjected to
column chromatography (silica gel 60–120 mesh, eluent
ethyl acetate/hexane) to afford 1-acryloxy piperidine or
1-acryloxy isobutylamine.
˚
General procedure for synthesis of unsaturated halides
using TBATFA
a,b-Unsaturated aromatic carboxylic acid (1 mmol) was
added to a solution of TBATFA (0.2 mmol) in 3 mL of
dichloroethane. After the mixture was stirred for 5 min at
room temperature, N-halosuccinimides (1.12 mmol) was
added in portions. The progress of the reaction was
monitored by TLC (eluent n-hexane). After completion of
the reaction, solvent was removed under reduced pressure
and the mixture was subjected to column chromatography
(silica gel 60–120 mesh, eluent n-hexane) to afford halo-
alkenes 1a–12a.
Spectral characteristics of products
1-Bromo-2-phenylalkene (1a). Lit.3,4b (NMR is identical).
1-Chloro-2-phenylalkene (1b). Lit.3,17 (NMR is identical).
1-Iodo-2-phenylalkene (1c). Lit.18,19 (NMR is identical).
General procedure for synthesis of a-(dihalomethyl)-
benzenemethanol
1-Bromo-2-(4-methoxyphenyl)alkene (2a). Lit.3,4b (NMR
is identical).
a,b-Unsaturated aromatic carboxylic acid (1 mmol) was
added to a solution of TBATFA (0.2 mmol) in 3 mL of
MeCN–H2O (1:1 v/v). After the mixture was stirred for
5 min at room temperature, N-halosuccinimide (2 mmol)
was added in portions. The progress of the reaction was
1-Chloro-2-(4-methoxyphenyl)alkene (2b). Lit.4b (NMR
is identical).
1-Iodo-2-(4-methoxyphenyl)alkene (2c). Lit.4b,18 (NMR is
identical).

D. Naskar, S. Roy / Tetrahedron 56 (2000) 1369–1377
1375
1-Bromo-1-methyl-2-(4-methoxyphenyl)alkene
(3a).
(3b).
Jˆ9 Hz), 8.23 (dd, 2H, Jˆ9, 4 Hz), 7.50–7.63 (m, 6H),
6.45 (d, 1H, Jˆ15 Hz). EIMS m/z (rel intensity): 237
(Mϩ, 58%), 202 (100%), 118 (19%), 100 (20%), 85 (7%),
71 (15%), 57 (25%), 43 (18%). IR (neat) cmϪ1: 1676 (w),
1603 (s), 1515 (s), 1265 (m).
Lit.4b (NMR is identical).
1-Chloro-1-methyl-2-(4-methoxyphenyl)alkene
Lit.4b (NMR is identical).
1-Iodo-1-methyl-2-(4-methoxyphenyl)alkene (3c). Lit.4b
(NMR is identical).
1-Bromo-2-(2-thienyl)alkene (11a). Oil. [Found: C, 30.28;
H, 2.32. C6H5IS requires C, 30.53, H, 2.13]. dH (200 MHz
CDCl3) 7.40 (d, 1H, Jˆ15 Hz), 7.12 (dd, 1H, Jˆ8, 4 Hz),
6.89 (d, 1H, Jˆ8 Hz), 6.87 (d, 1H, Jˆ8 Hz), 6.56 (d, 1H,
Jˆ15 Hz). EIMS m/z (rel intensity): 236 (Mϩ, 100%), 109
(85%), 65 (36%), 39 (22%). IR (neat) cmϪ1: 1640 (m), 1610
(w), 1500 (m), 1263 (s).
1-Bromo-2-(4-methylphenyl)alkene (4a). Lit.3,4b (NMR is
identical).
1-Bromo-2-methyl-2-phenylalkene (5a). Lit.3,4b (NMR is
identical).
1-Bromo-2-(2-furyl)alkene (12a). Oil. dH (200 MHz
CDCl3) 6.89 (d, 1H, Jˆ14 Hz), 6.79 (s, 1H), 6.71 (d, 1H,
Jˆ14 Hz), 6.36 (dd, 1H, Jˆ8, 4 Hz), 6.25 (d, 1H, Jˆ8 Hz).
EIMS m/z (rel intensity): 172 (Mϩ, 37%), 133 (70%), 97
(70%), 69 (69%), 55 (100%). IR (neat) cmϪ1: 1635 (m),
1608 (s), 1501 (m), 1260 (w).
1-Bromo-1-phenyl-2-phenylalkene (6a). Lit.3 (NMR is
identical).
1-Bromo-2-(4-chlorophenyl)alkene (7a). Lit.3,4b (NMR is
identical).
1-Bromo-4-phenyl-1,3-butadiene (8a). Lit.4b (NMR is
identical).
a-(Dibromomethyl)benzenemethanol (13). Low melting
solid. [Found: C, 34.18; H, 2.97. C8H8Br2O requires C,
34.32, H, 2.88]. dH (200 MHz CDCl3) 7.31 (s, 5H), 5.71
1-Bromo-2-(3,4-methylenedioxyphenyl)alkene (9a). Low
melting solid. [Found: C, 47.42; H, 3.33. C9H7O2Br requires
C, 47.61, H, 3.11]. dH (200 MHz CDCl3) 7.0 (d, 1H,
Jˆ14 Hz), 6.76 (d, 2H, Jˆ9 Hz), 6.72 (s, 1H), 6.58 (d,
1H, Jˆ14 Hz), d 5.98 (s, 2H). EIMS m/z (rel intensity):
226 (Mϩ, 99%), 147 (23%), 117 (15%), 89 (63%), 73
(15%), 63 (40%), 43 (27%). IR (neat) cmϪ1: 1680 (m),
1504 (s), 1264(vs), 1040 (s).
(d, 1H, Jˆ8 Hz), 4.94 (d, 1H, Jˆ8 Hz). IR (neat) cmϪ1
:
1591 (w), 1522 (s), 1267 (m).
a-(Dibromomethyl)-4-methoxybenzenemethanol (14).
Solid. [Found: C, 34.59; H, 3.39. C9H10Br2O2 requires C,
34.87, H, 3.25]. dH (200 MHz CDCl3) 7.34 (d, 2H, Jˆ9 Hz),
6.91 (d, 2H, Jˆ9 Hz), 5.74 (d, 1H, Jˆ8 Hz), 4.98 (d, 1H,
Jˆ8 Hz), 3.81 (s, 3H), 2.85 (br. 1H). EIMS m/z (rel inten-
sity): 310 (Mϩ, 10%), 150 (10%), 137 (100%), 135 (18%),
1-Chloro-2-(3,4-methylenedioxyphenyl)alkene (9b). Oil.
[Found: C, 58.97; H, 3.98. C9H7O2Cl requires C, 59.19,
H, 3.87]. dH (200 MHz CDCl3) 6.78 (d, 1H, Jˆ14 Hz),
6.71 (s, 1H), 6.70 (d, 2H, Jˆ9 Hz), 6.46 (d, 1H,
Jˆ14 Hz), 5.98 (s, 2H). EIMS m/z (rel intensity): 182
(Mϩ, 99%), 168 (7%), 126 (7%), 117 (7%), 89 (67%), 73
(18%), 63 (39%), 50 (15%). IR (neat) cmϪ1: 1676 (m), 1508
(m), 1240 (s), 1035 (w).
121 (55%), 109 (21%), 94 (11%), 77 (25%). IR (KBr) cmϪ1
1600 (m), 1520 (vs), 1264 (vs).
:
a-(Dichloromethyl)-4-methoxybenzenemethanol (15). Oil.
[Found: C, 48.67; H, 4.72. C9H10Cl2O2 requires C, 48.89, H,
4.56]. dH (200 MHz CDCl3) 7.34 (d, 2H, Jˆ9 Hz), 6.87 (d,
2H, Jˆ9 Hz), 5.72 (d, 1H, Jˆ8 Hz), 4.87 (d, 1H, Jˆ8 Hz),
3.80 (s, 3H), 2.50 (br. 1H). EIMS m/z (rel intensity): 220
(Mϩ, 3%), 137 (100%), 109 (28%), 94 (24%), 77 (33%). IR
(neat) cmϪ1: 1601 (m), 1519 (vs), 1264 (s).
1-Iodo-2-(3,4-methylenedioxyphenyl)alkene (9c). Low
melting solid. [Found: C, 39.28; H, 2.91. C9H7IO2 requires
C, 39.44, H, 2.58]. dH (200 MHz CDCl3) 7.80 (s, 1H), 7.30
(d, 1H, Jˆ14 Hz), 6.68 (d, 2H, Jˆ9 Hz), 6.61 (d, 1H,
Jˆ14 Hz), 5.96 (s, 2H). EIMS m/z (rel intensity): 274
(Mϩ, 94%), 147 (14%), 117 (10%), 89 (60%), 73 (12%),
63 (41%), 50 (16%). IR (neat) cmϪ1: 1687 (w), 1498 (vs),
1250 (m), 1050 (m).
a-(Diiodomethyl)-4-methoxybenzenemethanol (16). Oil.
[Found: C, 26.53; H, 2.28. C9H10I2O2 requires C, 26.76, H,
2.49]. dH (200 MHz CDCl3) 7.31 (d, 2H, Jˆ9 Hz), 6.85 (d,
2H, Jˆ9 Hz), 5.25 (d, 1H, Jˆ8 Hz), 4.60 (s, 1H), 3.81 (s,
3H), 2.78 (br. 1H). EIMS m/z (rel intensity): 404 (Mϩ, 6%),
254 (18%), 128 (51%), 57 (100%). IR (neat) cmϪ1: 1598
(m), 1522 (vs), 1266 (w).
1-Bromo-2-(9-anthracenyl)alkene (10a). Low melting
solid. [Found: C, 67.61; H, 4.14. C16H11Br requires C,
67.86, H, 3.92]. dH (200 MHz CDCl3) 8.45 (s, 1H), 8.23
(dd, 2H, Jˆ9, 4 Hz), 8.01 (dd, 2H, Jˆ9, 4 Hz), 7.91 (d,
1H, Jˆ16 Hz), 7.50 (m, 4H), 6.61 (d, 1H, Jˆ16 Hz).
EIMS m/z (rel intensity): 282 (Mϩ, 11%), 204 (100%),
101 (23%), 88 (7%), 43 (12%). IR (neat) cmϪ1: 1680 (w),
1600 (m), 1520 (vs), 1264 (s).
a-(Dibromomethyl)-a-methyl-4-methoxybenzenemetha-
nol (17). Oil. [Found: C, 36.80; H, 4.01. C10H12Br2O2
requires C, 37.07.45, H, 3.74]. dH (200 MHz CDCl3) 7.38
(d, 2H, Jˆ9 Hz), 6.80 (d, 2H, Jˆ9 Hz), 4.88 (s, 1H), 3.75 (s,
3H), 2.95 (br. 1H), 2.32 (s, 3H). IR (neat) cmϪ1: 1601 (w),
1521 (m), 1263 (s).
a-(Dibromomethyl)-4-methylbenzenemethanol (18). Low
melting solid. [Found: C, 36.58; H, 3.61. C9H10Br2O
requires C, 36.77, H, 3.43]. dH (200 MHz CDCl3) 7.26 (d,
2H, Jˆ9 Hz), 7.11 (d, 2H, Jˆ9 Hz), 5.72 (d, 1H, Jˆ8 Hz),
1-Chloro-2-(9-anthracenyl)alkene (10b). Low melting
solid. [Found: C, 79.98; H, 4.89. C16H11Cl requires C,
80.49, H, 4.65]. dH (200 MHz CDCl3) 8.55 (d, 2H,

1376
D. Naskar, S. Roy / Tetrahedron 56 (2000) 1369–1377
4.95 (d, 1H, Jˆ8 Hz), 2.85 (br. 1H), 2.35 (s, 3H). EIMS m/z
(rel intensity): 294 (Mϩ, 15%), 277 (75%), 198 (51%), 173
(19%), 121 (100%), 115 (8%), 105 (15%), 93 (73%), 91
72.38, H, 6.96]. dH (200 MHz CDCl3) 7.52 (d, 1H,
Jˆ16 Hz), 7.32 (d, 2H, Jˆ9 Hz), 6.92 (d, 2H, Jˆ9 Hz),
6.82 (s, 1H), 5.93 (d, 1H, Jˆ16 Hz), 3.88 (s, 3H), 3.80 (s,
3H), 2.1 (s, 3H). EIMS m/z (rel intensity): 232 (Mϩ, 39%),
201 (8%), 173 (100%), 158 (46%), 141 (8%), 129 (12%),
115 (14%). IR (KBr) cmϪ1: 1154 (vs), 1231 (s), 1492 (m),
1601 (m), 1677 (m), 2876 (w).
(55%), 77 (43%), 51 (12%), 43 (14%). IR (neat) cmϪ1
1601 (m), 1522 (vs), 1264 (s).
:
a-(Dibromomethyl)-3,4-methylenedioxybenzenemethanol
(19). Low melting solid. [Found: C, 33.24; H, 2.66.
C9H8Br2O requires C, 33.37, H, 2.49]. dH (200 MHz
CDCl3) 6.90 (s, 1H), 6.86 (d, 1H, Jˆ9 Hz), 6.79 (d, 1H,
Jˆ9 Hz), 6.0 (s, 2H), 5.70 (d, 1H, Jˆ8 Hz), 4.91 (d, 1H,
Jˆ8 Hz), 2.80 (br, 1H). EIMS m/z (rel intensity): 324 (Mϩ,
30%), 229 (22%), 151 (100%), 135 (30%), 93 (98%), 65
(81%), 63 (46%). IR (neat) cmϪ1: 1678 (w), 1503 (s), 1267 (m).
5-(4-Methylphenyl)-2,4-pentadienamide (28). Solid. dH
(200 MHz CDCl3) 7.35 (d, 2H, Jˆ9 Hz), 7.13 (d, 2H,
Jˆ9 Hz), 7.2 (m, 1H), 6.78 (m, 1H), 6.05 (d, 1H,
Jˆ14 Hz), 2.3 (s, 3H). EIMS m/z (rel intensity): 188 (Mϩ,
5%), 162 (100%), 117 (100%), 101 (81%), 73 (30%). IR
(KBr) cmϪ1: 985 (m), 1369 (s), 1631 (vs), 3108 (w).
a-(Dibromomethyl)-1-naphthylmethanol (20). Low
melting solid. [Found: C, 43.45; H, 3.21. C12H10Br2O
requires C, 43.67, H, 3.05]. dH (200 MHz CDCl3) 7.84
(m, 3H), 7.7 (d, 1H, Jˆ8 Hz), 7.48–7.56 (m, 3H), 6.08 (d,
1H, Jˆ8 Hz), 5.75 (d, 1H, Jˆ8 Hz). EIMS m/z (rel inten-
sity): 330 (Mϩ, 9%), 157 (100%), 129 (58%), 115 (9%). IR
(neat) cmϪ1; 1672 (w), 1598 (m), 1265 (vs).
5-(2-Thienyl)-2,4-pentadienoic acid (29). Solid. dH
(200 MHz CDCl3) 7.50 (dd, 1H, Jˆ12, 16 Hz), 7.31 (d,
1H, Jˆ8 Hz), 7.29 (d, 1H, Jˆ16 Hz), 7.15 (dd, 1H, Jˆ8,
4 Hz), 7.01 (m, 1H), 6.70 (dd, 1H, Jˆ12, 16 Hz), 6.00 (d,
1H, Jˆ16 Hz). EIMS m/z (rel intensity): 180 (Mϩ, 6%), 135
(70%) 134 (45%), 108 (14%), 97 (8%), 91 (70%), 65 (15%),
63 (30%), 45 (100%). IR (KBr) cmϪ1: 1155 (m), 1237 (vs),
1480 (s), 1665 (s), 2875 (w).
a-(Dibromomethyl)-a-phenyl-benzenemethanol (21). Oil.
[Found: C, 47.09; H, 3.21. C14H12Br2O requires C, 47.22, H,
3.40]. dH (200 MHz CDCl3) 7.98 (d, 2H, Jˆ8 Hz), 7.26–
7.55 (m, 8H), 6.3 (s, 1H). EIMS m/z (rel intensity): 356 (Mϩ,
5%), 258 (6%), 178 (15%), 105 (100%), 77 (91%). IR (neat)
cmϪ1: 1595 (m), 1525 (s), 1265 (m).
Piperine (30). Lit.13 (NMR is identical).
Pipergualamine (31). Lit.14 (NMR is identical).
Acknowledgements
a-(Dibromomethyl)-4-chlorobenzenemethanol (22). Low
melting solid. [Found: C, 30.08; H, 2.74. C8H7Br2ClO
requires C, 30.56, H, 2.25]. dH (200 MHz CDCl3) 7.31 (s,
4H), 5.67 (d, 1H, Jˆ8 Hz), 4.91 (d, 1H, Jˆ8 Hz). IR (neat)
cmϪ1: 1601 (w), 1520 (s), 1263 (m).
This work is supported by CSIR (Young Scientist Award
grant to S.R.) and DST. D.N. thanks CSIR for the award of a
senior research fellowship.
Methyl-5-(4-methylphenyl)-2,4-pentadienoate (23). Mp
98–99ЊC (lit.10c 98–99ЊC).
References
Ethyl-5-(4-methylphenyl)-2,4-pentadienoate (24). Oil.
[Found: C, 77.54; H, 7.61. C14H6O2 requires C, 77.73, H,
7.47]. dH (200 MHz CDCl3) 7.4 (dd, 1H, Jˆ11, 15 Hz), 7.3
(d, 2H, Jˆ8 Hz), 7.11 (d, 2H, Jˆ8 Hz), 6.7-6.9 (m, 2H), 5.9
(d, 1H, Jˆ15 Hz), 4.11 (q, 2H, Jˆ6 Hz), 2.2 (s, 3H), 1.20 (t,
3H, Jˆ6 Hz). EIMS m/z (rel intensity): 216 (Mϩ, 29%), 190
(24%), 171 (18%), 143 (100%), 128 (39%), 115 (27%), 91
(12%). IR (neat) cmϪ1: 1108 (s), 1154 (s), 1585 (m), 1277
(vs), 2877 (w).
1. (a) Borodin, B. Liebigs Ann. 1861, 119, 121. (b) Hunsdiecker,
H. C. Chem. Ber. 1942, 75, 291. (c) Chrich, D. In Comprehensive
Organic Synthesis; Trost, B. M., Steven, V. L. Eds.; Pergamon:
Oxford, 1991; Vol. 7, pp. 723–734. (d) Sheldon, R. A.; Kochi, J. K.
Org. React. (NY) 1972, 19, 326. (e) Mckillop, A.; Bromley; Taylor,
E. C. J. Org. Chem. 1969, 34, 1172. (f) Kochi, J. K. J. Am. Chem.
Soc. 1965, 87, 2500. (g) Cristol, S. J.; Firth, W. C., Jr. J. Org.
Chem. 1961, 26, 280. (h) Hassner, A.; Stumer, C. Organic
Syntheses based on Name and Unnamed Reactions; Pergamon:
Oxford, 1994; p. 183.
Methyl-5-(4-methoxyphenyl)-2,4-pentadienoate (25). Mp
125–126ЊC (lit.10c 125–126ЊC).
2. Trost, B. M. Angew. Chem., Int. Ed. Engl. 1995, 34, 259.
3. Typical yield 18% from silver cinnamate/bromine: Johnson,
R. J.; Ingham, R. K. Chem. Rev. 1956, 56, 219. Improved yield
in oxidative halo decarboxylation using stoichiometric PhIO/NBS/
acid/60ЊC: Graven, A.; Jorgensen, K. A.; Dahl, S.; Stanczak, A.
J. Org. Chem. 1994, 59, 3543.
4. (a) Chowdhury, S.; Roy, S. Tetrahedron Lett. 1996, 37, 2623.
(b) Chowdhury, S.; Roy, S. J. Org. Chem. 1997, 62, 199.
5. Garner, C. D.; Hughes, B. In Adv. Inorg. Chem. Radiochem.;
Emeleus, H. J., Sharpe, A. G., Eds.; 1975, Vol. 17, pp. 1–47.
6. The addition of bromine to the double becomes the major
reaction in polar solvent like tetrachloroethane, nitromethane:
Pizey, J. S. Synthetic Reagents; Ellis Horwood: Chichester, UK,
1974; Vol. 2, pp. 1–64.
5-(4-Methoxyphenyl)-2,4-pentadienoic acid (26). Mp 98–
100ЊC. dH (200 MHz CDCl3) 7.52 (dd, 1H, Jˆ11, 16 Hz),
7.45 (d, 2H, Jˆ8 Hz), 7.25 (d, 2H, Jˆ8 Hz), 6.7–7.0 (m,
2H), 5.95 (d, 1H, Jˆ16 Hz), 3.88 (s, 3H). EIMS m/z (rel
intensity): 204 (Mϩ, 39%), 162 (80%) 144 (23%), 115
(100%), 105 (14%), 91 (53%), 65 (32%), 63 (45%), 45
(70%). IR (KBr) cmϪ1: 1154 (m), 1230 (vs), 1492 (s),
1662 (s), 2877 (w).
Methyl-4-methyl-5-(4-methoxyphenyl)-2,4-pentadienoate
(27). Solid. [Found: C, 72.24; H, 7.10. C14H16O3 requires C,

D. Naskar, S. Roy / Tetrahedron 56 (2000) 1369–1377
1377
7. Naskar, D.; Chowdhury, S.; Roy, S. Tetrahedron Lett. 1998, 39,
699.
3901. (f) Crombie, L.; Hobbs, A. J. W.; Horsham, M. A.
Tetrahedron Lett. 1987, 28, 4875. (g) Crombie, L.; Horsham,
M. A.; Blade, R. J. Tetrahedron Lett. 1987, 28, 487.
12. (a) For review, see, Meijere, A. D.; Meyer, F. E. Angew.
Chem., Int. Ed. Engl. 1994, 33, 2379. (b) Heck, R. F.; Nolley,
J. P., Jr. J. Org. Chem. 1972, 37, 2320. (c) Heck, R. F.; Nolley,
J. P., Jr. J. Org. Chem. 1975, 40, 1083.
13. (a) Tsuboi, S.; Takeda, A. Tetrahedron Lett. 1979, 1043. (b)
Normant, H.; Fugeas, C. Compt. Rend. 1964, 258, 2846. (c)
Wenkert, E.; Hagaman, D. W.; Lewis, R. B.; Schell, F. M. J. Am.
Chem. Soc. 1971, 93, 6271.
14. (a) Chatterjee, A.; Dutta, C. P. Tetrahedron Lett. 1966, 1797.
(b) Okogun, J. I.; Khong, D. E. U. J. Chem. Soc., Perkin Trans. 1
1974, 2195.
15. Parrod, J.; Elles, J. Compt. Rend. 1956, 243, 1040; Chem.
Abstr. 1957, 51, 6641e.
8. (a) Weberl, L. M.; Headen, N.; Elslager, E. F. J. Med. Chem.
1967, 10, 366. (b) Bittner, S.; Gorodetsky, M.; Har-Paz, I.;
Mizarahi, Y.; Richmond, A. E. Phytochemistry 1977, 16, 143.
(c) Oritani, T.; Nanjyo, M.; Fujita, M.; Yamashita, K. Agric.
Biol. Chem. 1978, 42, 1437. (d) Chem. Abstr. 1978, 89, 163269.
9. (a) Dahiya, J. S.; Woods, D. L.; Tewari, J. P. Phytochemistry
1988, 28, 2159. (b) Miyakado, M.; Nakayama, I.; Ohno, N. Insec-
ticides of Plant Origin; American Chemical Society: Washington,
1989; Chapter 13, pp. 173–187. (c) Nakatani, N.; Inatani, R.;
Ohta, H.; Nishioka, A. Environ. Health Perspect. 1986, 67, 135.
10. (a) Crombie, L.; Pattende, G.; Stemp, G. Phytochemistry 1977,
16, 1437. (b) Huang, Y. Z.; Shi, L.; Yang, J.; Zhang, J. Tetrahedron
Lett. 1987, 28, 2159. (c) Myrboh, B.; Asokan, C. V.; Ila, H.;
Junjappa, H. Synthesis 1984, 50 and references therein.
11. (a) Huang, Y. Z.; Mo, X. S.; Wang, L. Tetrahedron Lett. 1998,
39, 419. (b) Abarbri, M.; Parrain, J. L.; Duchene, A. Synth.
Commun. 1998, 28, 239. (c) Lewis, N.; McKen, P. W.; Taylor,
R. J. K. Synlett 1991, 898. (d) Babudri, F.; Fiandanese, F.; Naso,
V.; Punzi, A. Tetrahedron Lett. 1994, 35, 2067. (e) Bernabeu,
M. C.; Chinchilla, R.; Najera, C. Tetrahedron Lett. 1995, 36,
16. Roy, S.; Das, I.; Bhanuprakash, K.; Gupta, B. D. Tetrahedron
1994, 50, 1847.
17. Karpaty, M. Bull. Soc. Chim. Fr. 1971, 1731.
18. Lee, G. C. M.; Tobin, B.; Holmes, J. M.; Harbourt, D. M.;
Garst, M. E. J. Am. Chem. Soc. 1990, 112, 9330.
19. Johnson, M. D.; Meeks, B. S. Chem. Commun. 1970, 1027.