The First Example of a Catalytic Hunsdiecker Reaction: Synthesis of β-Halostyrenes

Full text of DOI:10.1021/jo951991f

J . Org. Chem. 1997, 62, 199-200
199
Notes
Ta ble 1. LiOAc-Ca ta lyzed Ha lod eca r boxyla tion of
Th e F ir st Exa m p le of a Ca ta lytic
Hu n sd ieck er Rea ction : Syn th esis of
â-Ha lostyr en es†
r,â-Un sa tu r a ted Ca r boxylic Acid s 1 to Ha loa lk en es 2
w ith N-Ha losu ccin im id ea
entry
R1
R2
H
R3
H
X
time (h)
yield (%)b
1
2
3
4
5
H
Br
Cl
Br
Cl
I
Br
Br
Br
Br
Cl
4
12
0.2
6
2
2
0.5
1
6
61
55
91
65
58
86
92
88
41
37
Shantanu Chowdhury and Sujit Roy*
4-OMe
H
H
Metallo-Organic Laboratory, I&PC Division, Indian
Institute of Chemical Technology, Hyderabad 500007, India
6
4-Me
4-OMe
H
H
H
Me
H
H
Me
H
7c
8d
9
Received November 8, 1995
4-Cl
H
10
15
The halodecarboxylation of metal carboxylates with
molecular bromine, commonly known as the Hunsdiecker
reaction, is an extremely useful methodology in the
armory of an organic chemist for the synthesis of halo-
genated organic substrates.1 The efficacy of the reaction
has been improvised by several groups2 to include car-
boxylates of Hg(II), Tl(I), and Pb(IV) besides the original
Ag(I) of Hunsdiecker. In its present version, a modified
Hunsdiecker reaction can successfully accommodate ali-
phatic (1°, 2°, and 3°) and, to some extent, aromatic
carboxylic acids; however, major limitations include (a)
the necessity of high temperature; (b) very poor yields
in cases of substrates such as R,â-unsaturated carboxylic
acids;3 (c) the toxicity/hazard inherent with molecular
bromine and salts of mercury, thallium, lead, and silver;
and (d) the stringent ex-situ protocol of isolating and
purifying carboxylates in certain cases. Furthermore, the
art has not, heretofore, suggested or taught a reagent
system that is capable of mediating the Hunsdiecker
reaction in a catalytic fashion.4 The ever-increasing
consciousness among organic chemists toward atom
economy5 and our own interest6 in “naked-metal cata-
lysts” prompted us to investigate this problem. We
disclose in this report an efficient catalytic protocol for
the synthesis of â-halostyrenes from corresponding R,â-
unsaturated carboxylic acids and N-halosuccinimide us-
ing lithium acetate as catalyst.
a
Unless otherwise stated, the isomeric purity of the trans acids
and corresponding (E)-haloalkenes is >97% (vide 1H NMR).
Refers to isolated yields. c Halide E:Z ) 30:70. Acid t:c ) 87:
13; halide E:Z ) 82:18.
b
d
The other products identified are CO2 (ex-situ precipita-
tion with Ba(OH)2) and succinimide (GC, NMR). Re-
duced reaction time and higher yields of products are
particularly noteworthy for acids bearing electron-donat-
ing substitutents either in the aromatic ring or in the
alkene appendage (entries 3, 6-8) as compared to one
having an electron-withdrawing group (entry 9). Un-
catalyzed reaction, on the other hand, shows only 5-11%
conversion. An added feature of these reactions is the
moderate to good degree of stereospecificity; trans-
cinnamic acids give rise to the corresponding (E)-bro-
moalkenes as the major product.
The present methodology has been further extended
to the analogous dienoic acid 3, which affords the
corresponding bromide 4 in 60% isolated yield (eq 2).
Reactions of various R,â-unsaturated carboxylic acids
1 with NBS and catalytic LiOAc in acetonitrile-water
at ambient temperature afford the corresponding bro-
moalkenes 2 in good to excellent yields (eq 1, Table 1).
To gain further insight, various independent experi-
ments have been conducted, the results of which are
presented below: (a) while the reactions can be catalysed
by NaOAc, KOAc, and even CsOAc, the rates and product
yields are better with LiOAc; (b) analogous chloro- and
iododecarboxylations using NCS and NIS can be carried
out (entries 2, 4, 5, 10), the yield optimization being in
progress; and (c) the nitrone trapping experiment indi-
cates a dominance of the ionic pathway over the radical
route.
In the mechanistic front, the major question to be
addressed is, “What triggers the elimination of carbon
dioxide?” Mechanisms that require further investiga-
tions are (a) an acetate ion-promoted direct halodecar-
boxylation pathway and (b) carbon dioxide elimination
from an intermediate R-halo-â-lactone. The latter mech-
anism gains partial support from the results of the
reaction of 3-phenyl-but-2-eneoic acid (5), wherein we
could isolate the analogous â-halo-γ-lactone 6 in 85%
yield (eq 3). Compound 6 was fully characterized by
X-ray crystallography.
† Dedicated to Prof. Animesh Chakravorty on the occasion of his
60th birthday.
(1) (a) Crich, D. In Comprehensive Organic Synthesis; Trost, B. M.,
Steven, V. L., Eds.; Pergamon: Oxford, 1991; Vol. 7, pp 723-734. (b)
Sheldon, R. A.; Kochi, J . K. Org. React. (N. Y.) 1972, 19, 326.
(2) (a) Hassner, A.; Stumer, C. Organic Syntheses Based on Name
Reactions and Unnamed Reactions; Pergamon: Oxford, 1994; p 183.
(b) McKillop, A.; Bromley, D.; Taylor, E. C. J . Org. Chem. 1969, 34,
1172. (c) Kochi, J . K. J . Am. Chem. Soc. 1965, 87, 2500. (d) Cristol,
S. J .; Firth, W. C., J r. J . Org. Chem. 1961, 26, 280.
(3) (a) Typical yield, 17.5% from silver cinnamate/bromine: J ohnson,
R. J .; Ingham, R. K. Chem. Rev. 1956, 56, 219. (b) Improved yield in
oxidative halodecarboxylation using PhIO/NBS/acid/60 °C: Graven, A.;
J orgensen, K. A.; Dahl, S.; Stanczak, A. J . Org. Chem. 1994, 59, 3543.
(4) Catalytic decarboxylation is, however, widely studied: Darens-
bourg, D. J .; Holtcamp, M. W.; Longridge, E. M.; Khandelwal, B.;
Klausmeyer, K. K.; Reibenspies, J . H. J . Am. Chem. Soc. 1995, 117,
318 and references therein.
(5) Trost, B. M. Angew. Chem., Int. Ed. Engl. 1995, 34, 259.
(6) Chowdhury, S.; Samuel, P. M.; Das, I.; Roy, S. J . Chem. Soc.,
Chem. Commun. 1994, 1993.
S0022-3263(95)01991-8 CCC: $14.00 © 1997 American Chemical Society

200 J . Org. Chem., Vol. 62, No. 1, 1997
Notes
as a solid. The progress of the reaction was monitored by TLC
(silica gel, n-hexane-ethyl acetate 3:2). Usual workup by flash
chromatography (silica gel, n-hexane) afforded the haloalkene
2. All products were fully characterized by 1H NMR (200 MHz),
MS (EI, 70 eV), and comparison with authentic sample, wherever
possible.
In summary, we have shown that facile halodecarboxy-
lation of R,â-unsaturated carboxylic acids can be carried
out under catalytic conditions, thus further widening the
scope of the classical Hunsdiecker reaction.
Ack n ow led gm en t. Financial support from CSIR &
DST (SYS) (to S.R.) and UGC (fellowship to S.C.) is
gratefully acknowledged. This is IICT Communication
No. 3593.
Exp er im en ta l Section
Su p p or tin g In for m a tion Ava ila ble: 1H NMR and mass
spectra of haloalkenes 2 (entries 1, 3, 7), 5, and 6, 1H NMR
spectra of 2 (entries 2, 5, 6, 8, 9), UV spectra of 5, and ORTEP
diagram of 6 (17 pages). This material is contained in libraries
on microfiche, immediately follows this article in the microfilm
version of the journal, and can be ordered from the ACS; see
any current masthead page for ordering information.
Ma ter ia ls. Substituted trans-cinnamic acids were either
purchased (Aldrich, E-Merck) or synthesized via their esters;
the latter were obtained by a two-carbon Wittig protocol from
the corresponding aromatic aldehydes.
Gen er a l P r oced u r e. R,â-Unsaturated carboxylic acid 1 (2
mM) was added to a solution of LiOAc (0.2 mM) in 4.5 mL of
MeCN-H2O (97:3 v/v). After the mixture was stirred for 5 min
at room temperature, N-halosuccinimide (2.1 mM) was added
J O951991F