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of the alkene after its formation, was determined by
treating cis-ethyl cinnamate to the conditions of the dis-
solving metal reduction. In all attempts to affect the
isomerization of the product, no trans-cinnamate was
noted by nuclear magnetic resonance spectroscopy.
R
R
R
C
C
C C
R
Scheme 3. Equilibrium between cis- and trans-vinyl radical anions.
the cis-radical anion (Scheme 3).5 However, since the
trans-radical anion is considered to be more stable due
to steric hindrance, the equilibrium, once reached, still
favors the trans-radical anion. Thus, the trans-alkene
is not only the kinetic product (arising from the initially
formed trans-radical anion), but is also the thermo-
dynamic product of the reaction.
The pKa of the proton source in the reaction appears to
correlate well with the cis–trans ratio of the product.7 As
the pKa of the proton source increases, the time required
to consume the zinc increased and the percent trans-
alkene decreased. This correlation could imply that sur-
face phenomena described below, which are often over-
looked, may play a large role in the mechanism of the
reduction. Moreover, the rate determining step of the
mechanism, in the case of the dissolving zinc reductions,
may be the protonation of the anion instead of the radi-
cal anion. In such a case, the stereochemistry of the
product mixture may be explained by considering the
geometry of the carbanion–zinc ion paired intermediate
(Scheme 4). The trans ion pair, in equilibrium with the
cis ion pair, should be less fully ion paired with the zinc
because of steric requirements. In HCl, the proton
source is most likely H3O+, and the small hydronium
ion is more able to protonate the trans-isomer due to
its less fully ion paired nature and smaller size. The
trans-anion–zinc ion pair arising from the use of HCl
as a proton source may also be more solvent separated
due to the large quantity of chloride counterion in the
reaction mixture. The chloride anions would ion pair
with the zinc ion, resulting in a solvent separated ion
pair between the zinc cation and carbanion. In acetic
acid, however, the trans- and cis-anions should be more
tightly ion paired with zinc due to the lack of a large
quantity of anions in the reaction mixture. The larger
acetic acid proton source would then more rapidly pro-
tonate the more sterically accessible cis-anion–zinc ion
pair.
To further explore this assumption, we examined the
dissolving zinc metal reduction (using zinc powder in-
stead of Rieke zinc) of ethyl phenylpropiolate. Interest-
ingly, we noted a marked difference in product
stereochemistry as a function of the pKa of the added
proton source (Table 1).6 As shown in the table, when
the alkyne was treated with powdered zinc under condi-
tions similar to those used in Rieke zinc reductions, no
alkene products were detected. However, when the
methanol solvent was replaced with hydrochloric acid
(6.0 M), the reduction proceeded rapidly and in high
yield. Moreover, the stereochemistry of the product mix-
ture closely resembled that of the Rieke zinc reduction;
90% of the alkene product was the trans-alkene. When
hydrogen sulfate was used as the proton source, how-
ever, only 63% of the trans-isomer was produced. And
when acetic acid was used as the proton source, the
trans-isomer was found to be less than 10% of the prod-
uct alkene. A reduction in the percent of trans-alkene
formed in the reaction could be due to a slow forming
equilibrium between the more thermodynamically stable
and kinetically formed trans-radical anion and the cis-
radical anion as shown in Scheme 3. However, such an
argument does not account for the relatively high per-
cent of the cis-cinnamate ester formed when acetic acid
was used as the proton source.
A useful outcome of this study, in addition to an
increased understanding of the mechanism of the dis-
solving zinc metal reduction, is the ability to stereo-
chemically select either the cis- or trans-cinnamate
ester by simply changing the proton source in the
reduction of the corresponding alkyne. Moreover, the
Verification that the stereochemistry of the product
alkene was determined during the course of the reduc-
tion of the alkyne, and not as a result of isomerization
Table 1. The reduction of an alkyne with powdered zinc
CO2Et
Acid
H
+
C C CO2Et
THF, Zn
H
H
H
CO2Et
Transa (%)
Conva (%)
pKa
d
Reaction
Acid
1
MeOH
HCl
nd
90c
63
54
12
9
0
80
40
71
98
74
15.5
À7
2b
3
À
HSO4
H3PO4
2.0
4
2.1
4.2
5
PhCOOH
AcOH
6
4.8
a Determined by averaging multiple runs.
b Reaction performed at room temperature.
c Determined spectroscopically.
d Ref. 7.