236
Chemistry Letters 2000
Ni-Catalyzed Homocoupling of 3-Halopropenoates in the Presence of Water:
Formation of Hexenedioates
Martin Kotora,* Hiroshi Matsumura, and Tamotsu Takahashi*
Catalysis Research Center and Graduate School of Pharmaceutical Sciences, Hokkaido University
and CREST, Science and Technology Corporation (JST), Sapporo 060-0811
(Received September 16, 1999; CL-990794)
Homocoupling of (Z)-3-halopropenoates using a catalytic
amount of NiCl2 and Zn in the presence of water in pyridine
afforded a mixture of (Z)- and (E)-3-hexenedioates.
Homocoupling of organic halides is a well-established
route for the preparation of various symmetrical compounds
and is mediated or catalyzed in the presence of a reductant by a
number of transition metals such as Pd, Ni, etc.1 Dimerization
of 3-halopropenoic acids and their derivatives is of interest,
because the corresponding hexadienedioic acid derivatives are
biologically active compounds.2,3 So far, three methods have
been reported. The first two dimerization methods used stoi-
chiometric amounts of Ni(COD)2 in DMF4 or copper(I) thio-
phene-2-carboxylate5 to give hexadienedioates with retention of
the stereochemistry of the double bond. The third method was
carried out with 40 mol% of NiCl2 and Zn as a reductant in
HMPA; however, in this case a loss of stereochemistry was
observed.6 Nonetheless, a truly catalytic method for dimeriza-
tion of these compounds has not been developed yet. In this
regard, a potentially useful catalyst seemed to be NiCl2(PPh3)2
which was successfully used in another case involving halo-
propenoates.7
This was a quite unexpected result, and we set out to find the
reaction mechanism to explain the formation of 2. It was clear
that homocoupling products of 3-halopropenoates were formed
in the first step. However, in order to verify the homocoupling
of 3-halopropenoates, we carried out the following catalytic
reactions, since truely catalytic dimerization reaction of 3-halo-
propenoates has not been known yet as described above.
Homocoupling of alkyl (Z)-3-halopropenoates in the pres-
ence of a catalytic amount of NiCl2(PPh3)2 (10 mol%), Zn (1.5
equiv) in polar solvents proceeded with good selectivity to
afford hexadienedioates 5-7 (Scheme 1 and Table 1).
During the course of our study on Ni-catalyzed reactions of
halopropenoates, we found that when homocoupling of 1 was
carried out in pyridine in the presence of H2O and a catalytic
amount of NiCl2·6H2O, the products were hexenedioates 2 but
not hexadienedioates (Eq. 1). Moreover, the yield of this reac-
tion depended on halogen in the starting material: thus, 1a
afforded 2 in 5%, 1b in 50 (41% isol.), and 1c in 80 (66% isol.)
yield, respectively. This reaction also proceeded in the case of
(E)-3-chloropropenoates (3) (35% yield) (Eq. 2). When the
reaction was conducted with D2O, the corresponding deuterated
product 4 was obtained (Eq. 3).
Generally, the homocoupling proceeded in the several solvents
studied; however, it was sensitive to the reaction conditions as
well as to the quality of Zn. Thus, coupling of 1d in the pres-
ence of Zn that was left exposed to air for a longer period of
time (Entry 2) afforded substantial amount of isomerized prod-
ucts 6b + 7b. On the other hand, the use of freshly obtained Zn
powder (Entry 1) resulted in the clean formation of 5a.
Concerning reactions in THF, remarkable improvement in
yields was observed after treatment of the Zn suspension in
THF with TMSCl (0.2 equiv) (Entries 5 and 6), although the
formation of isomerized products 6b+7b was observed.
Homocoupling of 1e also proceeded smoothly (Entry 6) and
afforded the corresponding product 5c in 99% yield. (E)-3-
Iodopropenoate 3b showed the same reactivity as Z isomers as
Copyright © 2000 The Chemical Society of Japan
Kotora, Martin
