Mechanism and scope of the base-induced dehalogenation of (E)-diiodoalkenes

Article abstract of DOI:10.1002/ejoc.201402992

A wide range of nucleophiles have induced the elimination of iodine from (E)-diiodoalkenes to form alkynes under surprisingly mild conditions. The iodide anion is particularly efficient, and can drive the reaction to completion in less than 1 hour at room temperature in a polar aprotic solvent. Detailed investigations have suggested the reaction has a bimolecular polar mechanism. The deiodination reaction can be driven to completion with 1 equiv. of nucleophile and is partially catalytic with substoichiometric amounts of deiodinating reagent. Kinetic analysis of the stoichiometric iodide-induced reaction indicated an overall pseudo-first-order behavior. The reaction exhibited strong solvent effects, with much slower reactions observed in protic solvents than in polar aprotic solvents. The substrate dimethyl (2E)-2,3-diiodo-butene-2-dioate demonstrated orthogonal reactivity for either elimination or hydrolysis, depending on the solvent and nucleophile used. This reaction is a major pathway for all the diiodoalkenes examined, and represents a challenge and an opportunity for using these substrates in organic synthesis.

Full text of DOI:10.1002/ejoc.201402992

Job/Unit: O42992
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Date: 12-12-14 12:32:09
Pages: 9
FULL PAPER
DOI: 10.1002/ejoc.201402992
Mechanism and Scope of the Base-Induced Dehalogenation of
(
E)-Diiodoalkenes
[a]
[a]
[a]
[a]
Daniel Resch, Chang Heon Lee, Siew Yoong Tan, Liang Luo, and
Nancy S. Goroff*[
a]
Keywords: Reaction mechanisms / Lewis bases / Iodine / Elimination
A wide range of nucleophiles have induced the elimination
of iodine from (E)-diiodoalkenes to form alkynes under sur-
duced reaction indicated an overall pseudo-first-order be-
havior. The reaction exhibited strong solvent effects, with
prisingly mild conditions. The iodide anion is particularly ef- much slower reactions observed in protic solvents than in po-
ficient, and can drive the reaction to completion in less than
hour at room temperature in a polar aprotic solvent. De-
tailed investigations have suggested the reaction has a bimo-
lecular polar mechanism. The deiodination reaction can be
lar aprotic solvents. The substrate dimethyl (2E)-2,3-diiodo-
butene-2-dioate demonstrated orthogonal reactivity for
either elimination or hydrolysis, depending on the solvent
and nucleophile used. This reaction is a major pathway for
1
driven to completion with 1 equiv. of nucleophile and is par- all the diiodoalkenes examined, and represents a challenge
tially catalytic with substoichiometric amounts of deiodinat- and an opportunity for using these substrates in organic syn-
ing reagent. Kinetic analysis of the stoichiometric iodide-in-
thesis.
Introduction
Dihaloalkenes are popular substrates for transition-
Recently our group reported the elimination of iodine metal-catalyzed coupling reactions, and have been used to
from poly(diiododiacetylene) (PIDA, Figure 1) under mild prepare a variety of carbon-rich compounds such as tetra-
[
1]
[15–17]
conditions using Lewis basic pyrrolidine or under more ethynylethenes,
but there have been relatively few re-
extreme conditions such as pyrolysis.[ We also demon- ports on the chemistry of diiodoalkenes. Organ et al.
strated that the pyrrolidine-induced deiodination, pre- studied the coupling reactions of iodohaloethenes
viously unreported, is general for (E)-diiodoalkenes. Base- (CHI=CHX, X = Cl, Br, or I), and carried out Suzuki and
catalyzed dehalogenation of saturated vicinal dihaloalkanes Negishi reactions with iodochloro- and iodobromoethene,
2]
[
18]
is well known and has been extensively studied, especially but not diiodoethene.
Organ and co-workers also ob-
Yet there are served dehalogenation when mixing iodohaloethenes with
only a few reports of the dehalogenation of vicinal di- potassium hydroxide and [Pd(PPh ) ]. Other groups have
with the iodide anion as the nucleophile.[
3–12]
3
4
haloalkenes, and the known reactions involve much harsher tried similar coupling reactions and have had similar prob-
[
19,20]
conditions. Miller and Noyes first reported the elimination lems.
Each of these systems involved a palladium cata-
of iodine from diiodoethene using excess sodium iodide in lyst. However, our studies suggest that deiodination hap-
superheated methanol at temperatures of 109 °C and pens quite readily, and may not require the presence of pal-
[
13]
above.
Kosower and Ben-Shoshan more recently re- ladium.
ported the elimination of bromine from a dibromostilbene
The elimination of iodine from PIDA is particularly in-
triguing because it makes PIDA a potential precursor to
new all-carbon materials such as carbyne. In recent years,
all-carbon and carbon-rich polymers have attracted interest
in the areas of organic electronics and clean energy, as well
using NaI in acetone at reflux.[14]
[
21–23]
as for their fundamental science.
An understanding of
the mechanism and scope of iodine elimination will help
us identify conditions for complete deiodination to prepare
ordered all-carbon materials. The work presented here dem-
onstrates that the dehalogenation of diiodoalkenes occurs
under mild conditions and is very broad in scope. The de-
iodination of simple vicinal diiodoalkenes occurs at room
temperature with nucleophiles that are weak Brønsted
bases, including halide salts and amines. This previously un-
recognized reaction has significant consequences for chem-
Figure 1. Molecular structure of poly(diiododiacetylene) (PIDA).
[
a] Department of Chemistry, Stony Brook University,
Stony Brook, NY 11794-3400, USA
E-mail: nancy.goroff@stonybrook.edu
http://www.chem.stonybrook.edu/faculty/goroff.shtml
Supporting information for this article is available on the
WWW under http://dx.doi.org/10.1002/ejoc.201402992.
Eur. J. Org. Chem. 0000, 0–0
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D. Resch, C. H. Lee, S. Y. Tan, L. Luo, N. S. Goroff
FULL PAPER
ists who wish to use dihaloalkenes as precursors to carbon- amine, or iodide, whereas in protic solvents, the reaction
rich materials.
rate was greatly reduced (Table 2). In nonpolar solvents
such as toluene or cyclohexane, compound 1 remained
stable and did not react with pyrrolidine over a 2-day
period. Tetrabutylammonium iodide has very poor solubil-
ity in nonpolar solvents, and no reaction was observed
when it was mixed with compound 1 in cyclohexane or di-
ethyl ether. These observations are consistent with a polar
mechanism, in which hydrogen bonding in protic solvents
and ion-pairing in nonpolar solvents reduce the nucleophi-
licity of the Lewis base.
Results and Discussion
We previously reported that pyrrolidine induces deiodin-
ation in simple 1,2-diiodoalkenes such as compounds 1 and
3
in polar solvents such as THF.[1] In this work we found
that deiodination also occurred when compounds 1 and 3
were treated with tetrabutylammonium iodide (Scheme 1).
Compound 1 readily underwent deiodination with nBu NI
4
in [D ]nitrobenzene in about 1 hour, significantly faster
than the reaction with pyrrolidine. Diol 3 has poorer solu-
5
Table 2. Iodine elimination from alkene 1 in [D ]methanol.
4
Days
Conversion [%]
equiv. nBu
4
NI[a] 1 equiv. pyrrolidine[b]
bility than alkene 1, but if the reaction mixture in [D ]acet-
6
1
one was first heated to reflux to dissolve compound 3, the
deiodination with nBu NI reached 96% conversion in
1
2
3
5
46
59
66
75
5
4
12
28
63
48 hours.
[
4
a] Reagents and conditions: 0.275 m 1, 0.275 m nBu NI, room
temp., dark. [b] Reagents and conditions: 0.275 m 1, 0.275 m pyr-
rolidine, room temp., dark.
To gain a more detailed insight into the mechanism of
1
deiodination, H NMR spectroscopy was used for a kinetic
analysis. Monitoring the peaks for the protons α to the
double bond in diiodoalkene 1 or to the triple bond in alk-
yne 2, at δ = 2.53 and 2.13 ppm, respectively, allowed the
direct observation of both the starting material and the
product. Compound 1 reacts with tetrabutylammonium
iodide at the same rate in both [D ]nitrobenzene and [D ]-
Scheme 1. Elimination of iodine from diiodoalkene.
We investigated a wide range of solvents for the deiodin-
ation of alkene 1 (Table 1). Polar aprotic solvents promoted
the deiodination, whether induced by pyrrolidine, triethyl-
5
3
acetonitrile (see Figures S1 and S2 in the Supporting Infor-
mation). When equimolar amounts of nBu NI and alkene
4
1
react, the plot of the natural log of concentration versus
time (Figure 2) is linear throughout most of the reaction,
which indicates that the reaction follows first-order kinetics.
Table 1. Iodine elimination from alkene 1.[a]
Elimination/completion[b]
Unfortunately, neither the iodide nucleophile nor I
2
Solvent
Nucleophile
could be observed directly in the NMR experiments. Iodine
and triiodide could be observed by UV/Vis spectroscopy,
however, as long as the solvent used was acetonitrile rather
than nitrobenzene. By combining the UV/Vis absorption
and NMR spectroscopic data measured under the same
conditions, we obtained information on the relative concen-
trations of both the reactants and products. The kinetic
data in Figure 3 shows that triiodide is formed more slowly
than alkene 1 is consumed or alkyne 2 is formed. (The tri-
iodide signal dominates the UV spectrum, in part due to its
three-fold greater molar absorption coefficient as compared
Acetonitrile[
Nitromethane
c,d]
d,e]
I
I
I
I
–
yes/1 h
yes/2 h
yes/1 h
yes/no
yes/no
yes/3 d
yes/3 d
yes/3 d
yes/4 d
none
none
yes/15 h
none
none
yes/24 h
[
–
[
d]
–
Nitrobenzene
Methanol
–
–
2
-Propanol
,2-Dichloroethane
I
–
1
I
I
I
I
I
I
–
Dichloromethane
,2-Dimethoxyethane
Ethyl acetate
–
1
–
–
–
[
f]
Diethyl ether
Cyclohexane
[
f]
[
g]
THF
Toluene
Cyclohexane
pyrrolidine
pyrrolidine
pyrrolidine
triethylamine
[
24]
with that for iodine. ) These data imply a two-step process
in which iodide first reacts with alkene 1 to form alkyne 2
and molecular iodine, and at the same time release an iod-
[
h]
Nitrobenzene
[
a] Reagents and conditions: 0.137 m 1, 0.164 m nBu
temp., dark. [b] By TLC [silica/hexanes, R
hexanes/ethyl acetate (3:1), R
Supporting Information. [d] By NMR. [e] Reagents and conditions:
.275 m 1, 0.330 m nBu NI, room temp., dark. [f] Poor solubility of
nBu NI. [g] Reagents and conditions: 0.209 m 1, 0.418 m pyrrol-
4
NI, room
of 1 = 0.75, then silica/ ide ion, and then a second reaction between iodide and I
f
2
f
of 2 = 0.65]. [c] See Figure S2 in the leads to the consumption of iodide and the formation of
–
I . As the elimination reaction occurs, the concentration of
3
0
4
alkene 1 decreases faster than the concentration of iodide,
giving rise to pseudo-first-order behavior. The overall pro-
cess is summarized in Scheme 2.
4
idine, room temp., dark. [h] Reagents and conditions: 0.137 m 1,
.137 m triethylamine, room temp., dark.
0
2
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Base-Induced Dehalogenation of (E)-Diiodoalkenes
Figure 2. Kinetic plot of 0.275 m alkene 1 on reaction with 1 equiv.
of nBu NI in CD CN vesus time. A) NMR spectra. B) Rate law
4 3
analysis of the concentration (C) of alkene 1 from data in (A).
Concentrations were calculated relative to the initial concentration
2
of alkene 1. The red line indicates the linear least-squares fit (R =
0.994).
To further understand the nature of the reactive species
Figure 3. Kinetic data for the reaction of 0.275 m diiodoalkene 1
in the iodide-induced deiodination, we examined the reac-
tivity of the triiodide ion formed during the elimination. A
stoichiometric equivalent of tetrabutylammonium triiodide
was pre-formed by mixing tetrabutylammonium iodide and products based on data from (A) and Figure 2. Absolute concen-
3
molecular iodine for 10 min and then alkene 1 was added tration of I was calculated based on the standard curve shown in
and 0.275 m Bu
showing triiodide absorption at 362 nm and I
57 nm. B) Kinetic plot of the concentrations of reactants and
4
NI in acetonitrile. A) UV/Vis absorption spectra
2
absorption at
4
–
Figure S10 in the Supporting Information.
to the mixture. After 7 days, no deiodination of compound
3]
1
was observed. Slator[ found, in saturated diiodides, that
the rate of elimination slows as iodide complexes to iodine
to form triiodide. Our results further confirmed that tri-
iodide does not compete with iodide for reaction with al-
kene 1. An additional control experiment, performed with
1
.2 equiv. iodine and 2.4 equiv. nBu NI, also indicated that
4
Scheme 2. Proposed mechanism for the deiodination of diiodoalk-
the presence of triiodide does not inhibit the reaction (see enes.
Figure S4 in the Supporting Information).
We also examined reactions with an excess of alkene 1 to
probe further the role of the iodide/triiodide equilibrium substoichiometric nBu NI.
Table 3. Elimination of iodine from alkene 1 in the presence of
[a]
4
(
Table 3). These studies were carried out with two different
concentrations of alkene 1 (0.275 or 0.137 m) and either
.25 or 0.5 equiv. of iodide. More than one turnover per
[
1] [m]
[nBu
4
NI] [m]
[nBu
4
NClO
4
] [m]
Conv. [%]
0
0
0
.275
.275
.275
0.069
0.103
0.138
0.034
0.069
0.034
0.069
–
–
–
–
–
32
61
86
26
57
25
60
0
iodide was observed in these experiments, but the deiodin-
ation did not go to completion. These results are consistent
with the alkyne forming in a separate step from triiodide.
The more concentrated mixtures gave higher conversions,
which suggests an increased rate of elimination relative to
the formation of triiodide. The complexation with iodine
is thus not instantaneous. To test for salt effects, the non-
0.137
0.137
0
.137
.137
0.034
0.069
0
[
5 2
a] Reagents and conditions: [D ]PhNO , 1 day, room temp., dark.
nucleophilic salt tetrabutylammonium perchlorate was sion of the deiodination of alkene 1, consistent with Dillon’s
added to increase the ionic strength of the reaction mixture. observation in the case of vicinal dibromoalkanes that neu-
[
5]
The addition of this salt had no effect on the rate or conver- tral substrates are not susceptible to salt effects.
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D. Resch, C. H. Lee, S. Y. Tan, L. Luo, N. S. Goroff
FULL PAPER
The data in Figure 3 and Table 3 are consistent with two
separate steps: 1) The consumption of alkene 1 and 2) the
reaction of iodide with iodine to form triiodide, as shown in
Scheme 2. The relevant rates are described by the following
equations:
Because the concentration of I does not build up appre-
2
ciably over time, as indicated in Figure 3A, the concentra-
–
tion of I changes only slowly. Thus, the elimination reac-
tion follows pseudo-first-order kinetics, and in the substo-
ichiometric experiments, each iodide nucleophile is avail-
able, on average, to react with multiple diiodoalkenes.
Doubling the concentration of tetrabutylammonium iodide
in CD CN while maintaining the alkene concentration con-
stant (see Figures S2 and S3 in the Supporting Information)
led to a doubling of the reaction rate, consistent with a first- idine, room temp., dark, 15 h. See Figure S5 in the Supporting In-
3
Figure 4. NMR kinetic profile showing the formation of the pyrrol-
idinium species. Reaction conditions: 0.275 m 1, 0.275 m pyrrol-
formation for the kinetic analysis.
order behavior in nBu NI. Thus, the elimination appears to
4
be a bimolecular transformation involving one molecule of
iodide and one molecule of the alkene.
To test the reversibility of the reaction, tetrabutylammo-
nium iodide was mixed with iodine for 24 hours to form a
stoichiometric equivalent of triiodide, and then alkyne 2
was added to this mixture; the mixture was monitored for
3
days, but no detectable amount of diiodoalkene 1 was ob-
served. This experiment suggests that when iodine is fully
complexed as triiodide, the deiodination reaction is irrevers-
ible. In the absence of iodide, however, molecular iodine did
react with oct-4-yne (2) under these conditions (Scheme 3).
Monitoring the reaction by NMR spectroscopy indicated
95% conversion to alkene 1 in 12.5 hours.
Scheme 4. Proposed equilibria for the reaction of pyrrolidine with
diiodoalkene 1.
The role of the iodopyrrolidinium iodide (5) was studied
further by pre-forming it from a mixture of pyrrolidine and
I2. NMR studies of this reaction showed that the formation
of iodopyrrolidinium is completed in 3 hours (see Figure S6
in the Supporting Information). Once formed, complex 5
5
Scheme 3. Iodination of alkyne 2 in [D ]nitrobenzene.
The pyrrolidine-induced dehalogenation has a more did not induce diiodination, which suggests that iodopyrrol-
complicated reaction profile, with multiple possible nucleo- idinium iodide is a tightly bound, perhaps partially cova-
1
philes. Changes in the H NMR spectra show the formation lent, complex. However, when alkene 1 was treated with
of a pyrrolidinium species as the reaction progresses (Fig- substoichiometric quantities of pyrrolidine, more than one
ure 4). Amines are known to react with I and ICl to form turnover per pyrrolidine was observed (Table 4), which sug-
2
iodoammonium species,[
12,25]
but here we postulate that the gests that the iodopyrrolidinium cation and iodide anion do
iodopyrrolidinium ion forms directly from the reaction with not immediately combine to form complex 5 (Scheme 4).
the alkene. However, this reaction also yields the iodide ion, Nucleophiles other than iodide and pyrrolidine, such as
which may then react with the diiodoalkene, leading to mul- tetrabutylammonium fluoride, chloride, and bromide, can
tiple turnovers per pyrrolidine (Scheme 4). Kinetic studies also induce the deiodination of compound 1 (Figure 5). As
with a 1:1 ratio of pyrrolidine and alkene 1 demonstrated indicated by 1H NMR spectroscopy, the reaction of di-
higher than first-order kinetics for compound 1 (see Fig- iodoalkene 1 with tetrabutylammonium chloride or brom-
ure S5 in the Supporting Information). After 4 days of reac- ide resulted in the formation of the byproduct 4-chloro-5-
tion, the same mixture showed only 88% conversion.
iodo-4-octene (6) or 4-bromo-5-iodo-4-octene (7), respec-
4
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Base-Induced Dehalogenation of (E)-Diiodoalkenes
Table 4. Elimination of iodine from alkene 1 in the presence of
Table 5. Elimination of iodine from alkene 1 by using potassium
substoichiometric pyrrolidine.[
a]
salts.
[a]
Days
Conversion [%]
.25 equiv.[b]
Salt
Equiv.
Solvent
[D ]PhNO
toluene
[D ]PhNO
toluene
MeNO
MeNO
[D ]PhNO
Elimination Completion Time [d][b]
0
0.5 equiv.[c]
KI
KI
KBr
KBr
KClO
KPF
1
1
1
1
1.1
1
5
2
yes
no
yes
no
no
no
yes
yes
no
no
no
no
no
yes
1
[
c]
7
3
0
1
2
3
0
0
[d]
5
2
50
58
58
68
75
75
5
7
7
1
4
2
6
2
[
a] Reagents and conditions: 0.275 m alkene 1, [D
room temp. [b] 0.137 m pyrrolidine. [c] 0.069 m pyrrolidine.
5
]PhNO
2
, dark,
KOH
1.1
5
2
[
a] Reagents and conditions: x equiv. salt, x equiv. 18-crown-6,
room temp., dark. [b] By TLC [silica/hexanes, R of 1 = 0.75, then
silica/hexanes/ethyl acetate (3:1), R of 2 = 0.65]. [c] Approximately
half the KI remained dissolved. [d] Observation of 7 by NMR spec-
troscopy.
f
f
tively, with a corresponding reduction in the yield of alkyne
. These products indicate reversible dehalogenation, with
2
a much lower reactivity of the chloroiodo- and bromo-
iodoalkenes. The reaction with tetrabutylammonium fluor-
ide did not lead to the formation of the fluoroiodoalkene,
but the deiodination under these conditions was much
slower than with the other halides. Of all the nucleophiles
tested, the iodide ion promotes the fastest reaction.
reproduced in our laboratory. However, compound 8 under-
went complete deiodination to give the alkyne diester 10
when heated with tetrabutylammonium iodide in [D ]nitro-
5
benzene (Scheme 5).
Scheme 5. Orthogonal reactivity of diiododiester 8.
In contrast to the diiodoalkenes tested, dibromoalkene
11 did not undergo dehalogenation under the conditions
studied here. Mixing dibromide 11 with tetrabutylammo-
nium iodide in acetonitrile resulted in no reaction, even
when heated at reflux for a full day (Scheme 6).
Figure 5. Quantity of alkyne 2 produced by fluoride, chloride, and
bromide-induced deiodination.
The use of potassium halide salts in place of tetrabut-
ylammonium halides resulted in identical behavior, as long Scheme 6. Probing the reaction between dibromoalkene 11 and tet-
as 18-crown-6 was added to the reaction mixture to solubi- rabutylammonium iodide.
lize the salt (Table 5). On the other hand, as expected, the
non-nucleophilic salts KPF and KClO did not induce de-
Computational modeling of reactions with a large sol-
6
4
iodination in 1. The deiodination of compound 1 by potas- vent dependence is notoriously difficult, and we have not
sium hydroxide in the presence of 18-crown-6 in [D ]nitro- attempted to carry out extensive calculations on this sys-
5
benzene was rapid and went to completion. However, in tem. Rudimentary modeling at the Hartree–Fock, DFT, or
[
D ]methanol, there was no reaction with KOH after 2 days, MP2 level provided similar transition states for the gas-
4
consistent with the results for both pyrrolidine and tetrabut- phase concerted reaction of (E)-diiodoethene and iodide
ylammonium iodide in protic solvents. ion (see Figures S7 and S8 in the Supporting Information).
Diester 8 presents a particularly interesting case of or- We also evaluated an alternative stepwise mechanism, anal-
thogonal reactivity. Shah et al.[26] reported the nearly quan- ogous to an E1cb mechanism, in which the iodide first at-
titative hydrolysis of 8 in an aqueous alcohol hydroxide sys- tacks, removing one iodine from the substrate, leading to
tem with no observed deiodination, a result that we have the formation of a carbanion. However, in these calcula-
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D. Resch, C. H. Lee, S. Y. Tan, L. Luo, N. S. Goroff
tions, the carbanion intermediate is not a stationary point, Preparative-Scale Synthesis of (E)-4-Bromo-5-iodooct-4-ene (7): A
FULL PAPER
1
2 2
m IBr solution in CH Cl (4.5 mL, 4.5 mmol) was added to an
dissociating directly to acetylene and iodide ion (see Fig-
ure S9 in the Supporting Information).
argon-flushed and aluminium-foil-wrapped round-bottomed flask
equipped with a magnetic stirring bar. Compound 2 (0.60 mL,
0
.4506 g, 4.09 mmol) was then added. After 1 d, CH
was added to the solution. The organic layer was washed with 5%
Na (20 mL ϫ2) and then deionized water (30 mL ϫ2). The
organic layer was then dried with anhydrous MgSO and filtered
2 2
Cl (20 mL)
Conclusions
2 2 3
S O
4
Diiodoalkenes reacted with a variety of Lewis bases to
eliminate iodine and form the corresponding alkyne. The
reaction follows a concerted bimolecular mechanism, anal-
ogous to the E2 reaction, with nucleophilic attack on one
iodine precipitating elimination of the other as iodide. δ = 2.73–2.65 (m, 4 H), 1.67–1.54 (m, 4 H), 1.00–0.90 (m, 6
Stronger nucleophiles, such as iodide, reacted faster than H) ppm. C NMR (101 MHz, CDCl ): δ = 122.7, 121.7, 102.0,
before rotary evaporation. A short plug of silica, using 100% hex-
anes as the eluent, was used to separate alkyne 2 from the resulting
clear pale-yellow liquid. The product was an inseparable mixture
1
of cis and trans isomers of alkene 7. H NMR (400 MHz, CDCl
3
):
1
3
3
stronger bases, such as pyrrolidine, which indicates that the 100.0, 60.3, 52.6, 47.5, 46.9, 42.5, 34.5, 21.6, 20.9, 13.0, 11.8 ppm.
+
MS (EI): m/z = 316 [M] , 318. HRMS (EI): calcd. for C
[
8
H
14IBr
nucleophilicity of the Lewis base is a better predictor of
reactivity than Brønsted basicity, and the choice of solvent
strongly influenced the rate. The reaction is not catalytic
+
M] 315.93238; found 315.93257. The NMR spectra are provided
in the Supporting Information.
because the nucleophile reacted with the byproduct I to Testing for Triiodide-Induced Iodine Elimination: nBu
4
NI (0.0510 g,
2
0
.137 mmol) and iodine (0.0348 g, 0.137 mmol) were added to an
form an inactive species. These new insights suggest the
complete carbonization of PIDA may be possible under
mild conditions by using a simple halide salt in a polar
aprotic solvent.
5
aluminium-foil-wrapped vial. [D ]Nitrobenzene (1.0 mL) was
added and the vial was shaken. The mixture was subjected to sonic-
ation for 15 s to ensure homogeneity. Compound 1 (20.1 μL,
.0502 g, 0.137 mmol) was then added and the vial was shaken.
0
The contents of the vial were transferred to an NMR tube and an
1
initial NMR spectrum was recorded. A H NMR spectrum was
Experimental Section
measured on a daily basis for 1 week, but showed no change from
the initial spectrum of compound 1.
General Procedures: Air was purged from the NMR tubes used for
the kinetic experiments by displacement with argon gas prior to
the addition of any reagents. All other experiments were conducted
in closed small vials or NMR tubes under atmospheric conditions.
Prior to insertion in the spectrometer, the reaction mixture was kept
in the dark by wrapping aluminium foil around the NMR tube. The
temperature of the NMR kinetic experiments was held constant
at 25 °C by using a standard probe temperature controller. The
temperature of the UV/Vis kinetic experiments was ambient. To
determine the relative concentrations of starting material and prod-
uct, peaks corresponding to alkene 1 and alkyne 2 were integrated;
peak area overlap was not an issue. These integrals were compared
and the fractions of 1 and 2 were calculated to determine the per-
centage conversion. All solvents and reagents were used without
further purification. UV/Vis absorption spectra were collected with
a Jasco V630 spectrophotometer. Kinetic NMR data were collected
with a Bruker Avance 500 spectrometer equipped with CryoProbe
Prodigy, and were analyzed using Mestrenova software.
Measuring Triiodide Concentration by UV/Vis Spectroscopy: The
standard curve shown in Figure S10 in the Supporting Information
–
2
was prepared as follows: A stock triiodide solution of 1.00ϫ10
was prepared by dissolving nBu NI (0.1847 g, 0.500 mmol) and I
0.1269 g, 0.500 mmol) in acetonitrile to a volume of 50 mL in a
m
4
2
(
5
0-mL volumetric flask. Working solutions were prepared from the
–
4
–4
stock solution by serial dilution (1.00ϫ10 , 2.00ϫ10 ,
–
4
–4
–4
–4
3
.00ϫ10 , 4.00ϫ10 , 5.00ϫ10 , and 8.00ϫ10 m).
nBu NI (0.1016 g, 0.275 mmol) was loaded into a 1-mL volumetric
flask. Acetonitrile was introduced into the flask just below the
mark to dissolve nBu NI, followed by compound 1 (0.1002 g,
.275 mmol). The solution was quickly diluted to the mark, shaken,
4
4
0
and an aliquot of 36.0 μL was removed as an initial data point.
The aliquot was diluted in a 25-mL volumetric flask with aceto-
nitrile for UV/Vis analysis. The UV/Vis experiment was set-up as
a double-beam experiment with an acetonitrile blank. Aliquots of
36.0 μL were removed and diluted at the indicated intervals in Fig-
ure 3. Absolute concentrations were then calculated based on the
measured standard curve.
For the kinetics studies, it was of the utmost importance to measure
out the quantities of iodine and pyrrolidine carefully, given the
small scale of the reactions reported here. All kinetic experiments
were conducted by using solutions prepared in volumetric flasks to
ensure the concentrations could be accurately determined. Small
deviations in reagent concentrations were found to markedly affect
conversion percentages.
Testing for Iodination by Triiodide: nBu NI (0.0510 g, 0.137 mmol)
4
and iodine (0.0348 g, 0.137 mmol) were added to an aluminium-
foil-wrapped vial. [D ]Nitrobenzene (1.0 mL) was added and the
5
vial was shaken. The mixture was subjected to sonication for 15 s
to ensure homogeneity and then allowed to stand for 24 h. Com-
pound 2 (20.1 μL, 0.0151 g, 0.137 mmol) was then added and the
(
4E)-4,5-Diiodooct-4-ene (1) and dimethyl (2E)-2,3-diiodobut-2-
vial was shaken. The contents of the vial were transferred to an
enedioate (8) were prepared according to the procedure of Terentev
et al. (E)-2,3-Diiodobut-2-ene-1,4-diol (3) was prepared accord-
ing to the procedure of Hollins and Campos. All other starting
materials were used as purchased. The spectral data for oct-4-yne
1
[
27]
NMR tube and an initial NMR spectrum was recorded. A
H
[28]
NMR spectrum was recorded on a daily basis for 3 d, but showed
no change from the initial spectrum of compound 2.
(
(
2), but-2-yne-1,4-diol (4), and dimethyl acetylenedicarboxylate
10), and trans-2,3-dibromobut-2-ene-1,4-diol (11) matched the
Procedure for Dehalogenation by nBu
0.137 mmol) was added to an aluminium-foil-wrapped vial. [D
4
NF: TBAF hydrate (0.0358 g,
]-
5
corresponding spectra from the Spectral Database for Organic
Nitrobenzene (0.5 mL) was added, and the vial was shaken. The
mixture was subjected to sonication for 15 s to ensure homogeneity.
Compound 1 (0.0502 g, 0.137 mmol) was then added, and the vial
[
29]
Compounds. The NMR spectra for (E)-4-chloro-5-iodooct-4-ene
18]
(
6) matched the spectroscopic data reported by Organ et al.[
6
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Pages: 9
Base-Induced Dehalogenation of (E)-Diiodoalkenes
was shaken. The contents of the vial were transferred to a NMR
ation for 15 s to ensure homogeneity. Compound 8 (0.0546 g,
0.137 mmol) was then added, and the vial was shaken. After a few
minutes, a white solid precipitated out. The vial was heated and
kept at 45 °C to keep the white solid in solution. H NMR analysis
was conducted after 40 h, and showed compound 10 with a trace
amount of 8.
tube, and an initial NMR spectrum was recorded. 1H and
13
C
NMR spectra were collected on a daily basis for 8 d. The reaction
mixture was then left in the NMR tube wrapped in aluminium foil.
The triplet corresponding to 2 at δ = 2.04 ppm and the multiplet
corresponding to 1 at 2.45–2.50 ppm were integrated. The conver-
sion was calculated by using the integral of 2 expressed as a percen-
tage of the total integral sum. A change in color from pale yellow
to a deep reddish-brown was observed. The NMR spectra are given
in the Supporting Information.
1
nBu
4
NI-Induced Iodine Elimination from Diol 3: Compound 3
]acetone (0.5 mL), and tetrabutylam-
(
0.0469 g, 0.138 mmol), [D
6
monium iodide (0.0510 g, 0.138 mmol) were mixed together in an
aluminium-foil-wrapped vial. The mixture was heated at reflux to
Procedure for Dehalogenation by nBu
4
NCl: TBACl (0.0381 g, dissolve all components. The reaction mixture was then cooled to
]-
room temperature and allowed to stand without stirring in the dark
0.137 mmol) was added to an aluminium-foil-wrapped vial. [D
5
1
13
Nitrobenzene (0.5 mL) was added, and the vial was shaken. The
mixture was subjected to sonication for 15 s to ensure homogeneity.
Compound 1 (0.0502 g, 0.137 mmol) was then added, and the vial
was shaken. The contents of the vial were transferred to an NMR
at room temperature for 48 h. H and C NMR analysis showed
96% conversion to compound 4.[
29]
4
Reaction of nBu NI and Diol 11: Compound 11 (0.339 g,
1
.38 mmol) was added to acetonitrile (5 mL) in a round-bottomed
1
13
tube, and an initial NMR spectrum was recorded. H and
C
flask equipped with a magnetic stirring bar. Tetrabutylammonium
iodide (0.510 g, 1.38 mmol) was added to the solution, and the re-
action mixture was heated to 80–85 °C. After 1 d the solvent was
NMR spectra were collected on a daily basis for 8 d. The reaction
mixture was then left in the NMR tube, wrapped in aluminium foil.
The triplet corresponding to 2 at δ = 2.04 ppm and the multiplet at
5
removed in vacuo. The crude sample was dissolved in [D ]nitroben-
2.45–2.58 ppm corresponding to 1 at the start of experiment and
1
zene and subjected to H NMR analysis, which showed only com-
to 6 at the end of the experiment were integrated to determine the
conversion. A change in color from pale yellow to a deep reddish-
brown was observed. The NMR spectra are given in the Supporting
Information.
pound 11.[
29]
Testing for Iodopyrrolidinium-Induced Iodine Elimination: Iodine
(0.140 g, 0.550 mmol) was mixed with pyrrolidine (45.2 μL,
0
5
.0391 g, 0.550 mmol) and [D ]nitrobenzene in a 1-mL volumetric
Procedure for Dehalogenation by nBu
4
NBr: TBABr (0.0442 g,
]-
flask. This solution was allowed to stand at room temperature in
the dark for 24 h to ensure complete reaction of iodine and pyrrol-
idine. An aliquot of 0.50 mL of this stock solution was placed in a
clean 1-mL volumetric flask, followed by the addition of com-
pound 1 (40.0 μL, 0.1000 g, 0.275 mmol). The solution was diluted
0.137 mmol) was added to an aluminium-foil-wrapped vial. [D
5
Nitrobenzene (0.5 mL) was added, and the vial was shaken. The
mixture was subjected to sonication for 15 s to ensure homogeneity.
Compound 1 (0.0502 g, 0.137 mmol) was then added, and the vial
was shaken. The contents of the vial were transferred to a NMR
1
13
with [D
5
]nitrobenzene, immediately transferred to an NMR tube,
tube, and an initial NMR spectrum was recorded. H and
C
and an initial spectrum was collected after 15 min. The mixture
was observed by H and C NMR for 3 d. Compound 1 was found
to remain stable over the 3-day period.
NMR spectra were collected on a daily basis for 8 d. The reaction
mixture was then left in the NMR tube, wrapped in aluminium foil.
The triplet corresponding to 2 at δ = 2.04 ppm and the multiplet at
1
13
2.45–2.58 ppm corresponding initially to compound 1 and later to
Kinetic Investigation of the Reaction Between Iodine and Pyrrolidine:
compound 7 were integrated to calculate the conversion. A change
in color from pale yellow to a deep reddish-brown was observed.
The NMR spectra are given in the Supporting Information.
Iodine (0.1396 g, 0.550 mmol) was dissolved in [D ]nitrobenzene in
a 2-mL volumetric flask. A 1.0-mL aliquot of the 0.275 m solution
was transferred to an NMR tube. Pyrrolidine (22.6 μL, 0.0196 g,
5
0
.275 mmol) was then added to the NMR tube, and the tube was
Testing for KOH-Induced Iodine Elimination in [D
pound 1 (20.0 μL, 0.0501 g, 0.138 mmol) was added to MeOH
0.5 mL) in a round-bottomed flask equipped with a magnetic stir-
ring bar. An aqueous solution of 0.5 m KOH (0.83 mL, 0.4 mmol)
was then added to the flask. After 48 h, it was neutralized by the
addition of an aq. 0.5 m HCl solution (0.83 mL). The solution was
extracted with hexanes (1.0 mL ϫ3). The organic phase was
4
]MeOD: Com-
shaken. The time elapsed between the addition of pyrrolidine and
collection of the first H NMR spectrum was 3 min. A total of 55
spectra were collected at 3.3 min intervals to obtain a kinetic profile
1
(
(
see Figure S6 in the Supporting Information). A change in color
from pale yellow to a deep reddish-brown was observed.
Reaction of Compound 2 and Iodine: [D ]Nitrobenzene (0.6 mL)
and iodine (0.0350 g, 0.138 mmol) were added to an aluminium-
foil-wrapped vial. The mixture was subjected to sonication for
5
washed with brine (1.0 mL ϫ3) and then dried with MgSO
solvent was removed in vacuo. The residue was dissolved in [D
4
. The
]-
5
nitrobenzene for NMR analysis. Only compound 1 was observed
30 min to ensure homogeneity. Compound
2
(0.0151 g,
1
in the H NMR spectrum.
0.137 mmol) was then added, and the vial was shaken. The con-
Triethylamine-Induced Iodine Elimination: Triethylamine (0.0139 g,
tents of the vial were transferred to an NMR tube and an initial
0.137 mmol) was placed in an aluminium-foil-wrapped vial, [D
5
]- NMR spectrum was collected. The time elapsed between mixing of
1
nitrobenzene (0.5 mL) was added, and the vial was shaken. Com-
pound 1 (0.0502 g, 0.137 mmol) was then added and the contents
of the vial were mixed by shaking. The contents of the vial were
transferred to an NMR tube, and an initial NMR spectrum was
reagents and collection of the initial spectrum was 7 min. A
H
NMR spectrum was recorded every 15 min for 12.5 h. At 12.5 h the
reaction showed 95% conversion of compound 2 into compound 1.
Representative Procedure for Experiments with Substoichiometric
1
recorded. A H NMR spectrum was collected after 1 d, and only
nBu
4
NI: NBu
4
NI (0.0442 g, 0.137 mmol) was added to a 1-mL vol-
]nitrobenzene. The solution was
compound 2 was observed. A change in color from pale yellow to
a deep reddish-brown was observed.
umetric flask and diluted with [D
5
thoroughly shaken and then subjected to sonication for 15 s to en-
sure homogeneity. An aliquot (0.5 mL) of this solution was then
added to an NMR tube. The sample was inserted into the NMR
instrument for locking and shimming, then ejected so that com-
nBu
0.0510 g, 0.137 mmol) and [D
aluminium-foil-wrapped vial. The mixture was subjected to sonic-
4
NI-Induced Iodine Elimination from Diester 8: nBu
4
NI
(
5
]PhNO (0.5 mL) were added to an
2
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Job/Unit: O42992
/KAP1
Date: 12-12-14 12:32:09
Pages: 9
D. Resch, C. H. Lee, S. Y. Tan, L. Luo, N. S. Goroff
FULL PAPER
pound 1 (20.0 μL, 0.0501 g, 0.137 mmol) could be added to the
tube. H NMR spectra were recorded initially and after 24 h. The
triplets at δ = 2.53 ppm corresponding to 1 and at 2.06 ppm corre-
sponding to 2 were integrated to calculate the conversion. A change
in color from pale yellow to a deep reddish-brown was observed.
[2] L. Luo, C. Wilhelm, C. N. Young, C. P. Grey, G. P. Halada, K.
Xiao, I. N. Ivanov, J. Y. Howe, D. B. Geohegan, N. S. Goroff,
Macromolecules 2011, 44, 2626.
1
[3] A. Slator, J. Chem. Soc. Trans. 1904, 85, 1697.
[4] R. T. Dillon, W. G. Young, H. J. Lucas, J. Am. Chem. Soc.
1
930, 52, 1953.
Representative Procedure for Experiments with Substoichiometric
Pyrrolidine: Pyrrolidine (22.6 μL, 0.0196 g, 0.275 mmol) was added
to a 1-mL volumetric flask and diluted with [D ]nitrobenzene. The
5
solution was thoroughly shaken and then subjected to sonication
for 15 s to ensure homogeneity. A 1-mL syringe was used to extract
[
5] R. T. Dillon, J. Am. Chem. Soc. 1932, 54, 952.
[6] S. Winstein, D. Pressman, W. G. Young, J. Am. Chem. Soc.
1
939, 61, 1645.
[7]
H. L. Goering, H. H. Espy, J. Am. Chem. Soc. 1955, 77, 5023.
[8] J. Hine, W. H. Brader, J. Am. Chem. Soc. 1955, 77, 361.
[9] E. Baciocchi, A. Schiroli, J. Chem. Soc. B 1969, 554.
[10] C. S. T. Lee, I. M. Mathai, S. I. Miller, J. Am. Chem. Soc. 1970,
92, 4602.
0
.50 mL of the solution, which was diluted in another 1-mL volu-
metric flask to make a stock solution with a concentration of
.14 m. An aliquot of 0.50 mL was then extracted from the diluted
solution and introduced into an NMR tube. Compound 1
0.0501 g, 0.137 mmol) was then added by syringe into the NMR
0
[11] E. Baciocchi, C. Lillocci, J. Chem. Soc. Perkin Trans. 2 1973,
(
38.
1
1
[12] E. Baciocchi, C. Lillocci, J. Chem. Soc. Perkin Trans. 2 1975,
tube, and an initial H NMR spectrum was recorded. A H NMR
spectrum was collected on a daily basis for 3 d. In between, the
reaction mixture was kept in the NMR tube, covered with alumin-
ium foil. The triplets at δ = 0.83 ppm corresponding to alkene 1
and at 0.92 ppm corresponding to alkyne 2 were integrated to de-
termine the percentage of compound 2. A change in color from
pale yellow to a deep reddish-brown was observed.
802.
[13] S. I. Miller, R. M. Noyes, J. Am. Chem. Soc. 1952, 74, 3403.
[14] E. M. Kosower, M. Ben-Shoshan, J. Org. Chem. 1996, 61, 5871.
[15] R. R. Tykwinski, U. Gubler, R. E. Martin, F. Diederich, C.
Bosshard, P. Günter, J. Phys. Chem. B 1998, 102, 4451.
[
16] R. Spreiter, C. Bosshard, G. Knöpfle, P. Günter, R. R. Tykwin-
ski, M. Schreiber, F. Diederich, J. Phys. Chem. B 1998, 102, 29.
Representative Procedure for Iodine Elimination by Potassium Salts:
KBr (0.0160 g, 0.137 mmol) and 18-crown-6 (36.1 mg, 0.137 mmol)
were added to an aluminium-foil-wrapped vial. Toluene (1 mL) was
added, and the vial was shaken. The mixture was subjected to son-
ication for 1 min to ensure homogeneity. Compound 1 (0.0501 g,
[17] J. Anthony, A. M. Boldi, Y. Rubin, M. Hobi, V. Gramlich,
C. B. Knobler, P. Seiler, F. Diederich, Helv. Chim. Acta 1995,
78, 13.
[
18] M. G. Organ, H. Ghasemi, C. Valente, Tetrahedron 2004, 60,
9453.
[
[
[
19] B. C. Ranu, K. Chattopadhyay, Org. Lett. 2007, 9, 2409.
20] Y. T. L. Liang, Y. Zhang, J. Li, Synthesis 2008, 24, 3988.
21] Y. M. Lin, C. Dimitrakopoulos, K. A. Jenkins, D. B. Farmer,
H. Y. Chiu, A. Grill, P. Avouris, Science 2010, 327, 662.
22] A. Du, Z. Zhu, S. C. Smith, J. Am. Chem. Soc. 2010, 132, 2876.
0
.137 mmol) was then added, and the vial was shaken. The reaction
was monitored by TLC (SiO /hexanes) for 5 d, with no observed
change (compound 1 has R = 0.7, whereas compound 2 has R
under these conditions). In addition, there was no observed
change in color.
2
f
f
=
0
[
[23] W. A. Chalifoux, R. R. Tykwinski, Nature Chemistry 2010, 2,
967.
Supporting Information (see footnote on the first page of this arti-
cle): Kinetic NMR spectroscopic data, computational details, and
additional NMR spectra.
[
24] A. Semnani, H. R. Pouretedal, M. H. Keshavarz, Bull. Korean
Chem. Soc. 2006, 27, 886.
[
25] T. Tassaing, M. Besnard, J. Phys. Chem. A 1997, 101, 2803.
26] A.-u.-H. A. Shah, Z. A. Khan, N. Choudhary, C. Lohölter, S.
Schäfer, G. P. L. Marie, U. Farooq, B. Witulski, T. Wirth, Org.
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[
Acknowledgments
[27] A. O. Terentev, D. A. Borisov, I. B. Krylov, G. I. Nikishin,
The authors thank Dr. Vladimir Fainzilberg for helpful discussions.
The authors thank the National Science Foundation (CHE-
Synth. Commun. 2007, 37, 3151.
[
[
28] R. A. Hollins, M. P. A. Campos, J. Org. Chem. 1979, 44, 3931.
29] SDBSWeb: http://riodb01.ibase.aist.go.jp/sdbs/, National Insti-
tute of Advanced Industrial Science and Technology, accessed
June 6, 2012.
0911540) for support of this research.
[
1] L. Luo, D. Resch, C. Wilhelm, C. N. Young, G. P. Halada, R. J.
Gambino, C. P. Grey, N. S. Goroff, J. Am. Chem. Soc. 2011,
Received: July 25, 2014
133, 19274.
Published Online: ᭿
8
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© 0000 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Eur. J. Org. Chem. 0000, 0–0

Job/Unit: O42992
/KAP1
Date: 12-12-14 12:32:09
Pages: 9
Base-Induced Dehalogenation of (E)-Diiodoalkenes
Dehalogenation of Diiodoalkenes
D. Resch, C. H. Lee, S. Y. Tan, L. Luo,
N. S. Goroff* .................................... 1–9
Mechanism and Scope of the Base-Induced
Dehalogenation of (E)-Diiodoalkenes
A diiodoalkene diester undergoes hydroly-
sis on treatment with KOH, but eliminates
iodine on reaction with iodide salts. This
orthogonal reactivity is just one example of
the interesting chemistry that arises from
the reactions of diiodoalkenes with Lewis
bases. The mechanism for this mild reac-
tion has been studied experimentally.
Keywords: Reaction mechanisms / Lewis
bases / Iodine / Elimination
Eur. J. Org. Chem. 0000, 0–0
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9