Aza versus Oxophilicity of SmI2: A Break of a Paradigm

Article abstract of DOI:10.1002/chem.201703394

Ligands that coordinate to SmI₂ through oxygen are prevalent in the literature and make up a significant portion of additives employed with the reagent to perform reactions of great synthetic importance. In the present work a series of spectroscopic, calorimetric and kinetic studies demonstrate that nitrogen-based analogues of many common additives have a significantly higher affinity for Sm than the oxygen-based counterparts. In addition, electrochemical experiments show that nitrogen-based ligands significantly enhance the reducing power of SmI₂. Overall, this work demonstrates that the use of nitrogen-based ligands provides a useful alternative approach to enhance the reactivity of reductants based on Sm^II.

Full text of DOI:10.1002/chem.201703394

A Journal of
Accepted Article
Title: Aza vs. Oxophilicity of SmI2: A Break of a Paradigm
Authors: Robert A Flowers, Shmaryahu Hoz, and Sandeepan Maity
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Aza vs. Oxophilicity of SmI : A Break of a Paradigm
2
Sandeepan Maity,[a,b] Robert A. Flowers II* and Shmaryahu Hoz*
[a]
[b]
Abstract: Ligands that coordinate to SmI
2
through oxygen are
the general structure of glycols (henceforth referred to as G-
ligands). Several diagnostic tools including: a) spectral analyses,
b) ligand competition experiments, c) isothermal titration
calorimetry and d) cyclic voltammetry are used to demonstrate
the high affinity of nitrogen-based ligands for Sm(II).
prevalent in the literature and make up a significant portion of
additives employed with the reagent to perform reactions of great
synthetic importance. In the present work a series of spectroscopic,
calorimetric and kinetic studies demonstrate that nitrogen-based
analogs of many common additives have a significantly higher
affinity for Sm than the oxygen-based counterparts. In addition,
electrochemical experiments show that nitrogen-based ligands
Results and Discussion
2
significantly enhance the reducing power of SmI . Overall, this work
demonstrates that the use of nitrogen-based ligands provides a
useful alternative approach to enhance the reactivity of reductants
based on Sm(II).
The most straightforward approach to examine coordination of
ligands to SmI is visible spectroscopy and this technique is also
2
the fastest and most straightforward tool to apply. In general,
spectral changes of the two broad absorptions at 600 nm
provide a clear indication of ligand complexation to the SmI
Previous work on ligands that coordinate through oxygen
HMPA, MeOH, H O) display a broadening or merging of the
absorptions at 600 nm.
higher affinity ligands displays a broadening of the absorptions
at a much lower additive: SmI ratio than lower affinity ligands.
2
.[2]
Introduction
(
2
[
6]
Typically, the visible spectrum of
2
The most important advantage of samarium diiodide (SmI ) as a
reducing agent is its versatility in a wide range of reductions and
bond-forming reactions that proceed through electron transfer.[1]
One of the unique features of the reagent is that its reactivity is
controlled by additives that act as ligands.[2] In nearly every
2
Recent work in our groups has provided evidence that amines
and other nitrogen-based ligands may have higher affinities than
originally indicated from previous studies in the literature.[7] To
instance, ligands accelerate or alter the reactivity of SmI
through the interaction of an oxygen atom on the additive
ligand).[2, 3] Although nearly forty years have elapsed since SmI
2
initially examine the affinity of an amine, we chose n-BuNH
test ligand. Figure shows the results of increasing
concentrations of n-BuNH on the visible spectrum of 2 mM
2
as a
1
(
2
2
was introduced into organic chemistry, three recent reviews
concerning additives used in its reactions, describe only oxygen,
2
solution of SmI .
but not nitrogen based ligands as additives in reactions.[2, 1k]
A
0 M
0.05 M
0.3 M
0.1 M
0.4 M
0.3
great deal of the success in using additives that coordinate to
Sm through interaction with oxygen has been proposed to be a
consequence of the oxophilicity of Sm(II).[4, 3h, 3i, 3j, 3k] As a
consequence, nitrogen based ligands are only sporadically
described in the literature.[5] One of the classical example of
nitrogen based ligand is sodium or potassium salt of bis
0.2 M
0.2
0.1
(
trimethylsilyl) amide which forms strong complex with Sm(II)
resulting in thermodynamically stronger reductant.[5b]
0
In the present paper, we show that in contrast to the
aforementioned literature precedent, SmI is significantly more
2
azaphilic than oxophilic and consequently aza ligands are much
more effective than the oxygen ligands in enhancing the
reducing power of the reagent. The work described herein
presents studies on mono as well as bidentate ligands having
400
500
l/ nm
600
700
2 2
Figure 1. The effect of n-BuNH on the spectrum of SmI (2 mM).
Next, the oxygen analog n-BuOH was examined at the same
concentrations. Surprisingly, the alcohol had no significant
[
[
a]
b]
Dr. Sandeepan Maity and Prof. Robert A. Flowers II
Department of Chemistry
Lehigh University
2
impact on the spectrum of SmI (see SI, Figure S1). It should be
2
pointed out that water and MeOH do complex to SmI and
significantly affect its spectrum.[
6a,c]
However higher alcohols,
6
E Packer Ave, Bethlehem, Pennsylvania-18015, USA
apparently because of steric hindrance, do not. Similarly, while
the cyclic diether dioxane has no effect on the spectrum (Figure
S2), morpholine and pyrrolidine have significant effect on it
E-mail: rof2@lehigh.edu
Prof. Shmaryahu Hoz
Department of Chemistry
Bar-Ilan University
Geha Road, Ramat Gan-52900, Israel.
Email: shoz@biu.ac.il
(
Figures 2). Piperidine also has a significant impact on the
spectrum (see SI, Figure S3).
Supporting information for this article is given via a link at the end of
the document.
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(a)
0
M
0.01 M
0.04 M
0.02 M
0.05 M
0
M
0.05 M
0.3 M
0.1 M
0.4 M
0.3
0.2
0.1
0
0.3
0.2
0.1
0
0.2 M
.5 M
0.03 M
0
0
.06 M
400
500
l/ nm
600
700
400
500
600
700
(b)
l/ nm
2
Figure 3. The effect of EG on the spectrum of SmI (2 mM).
0
M
0.002 M
0.02 M
0.08 M
0.005 M
0.04 M
0.1 M
0.3
0.2
0.1
0
0.01 M
0.06 M
0.12 M
Interestingly, when one of the oxygen atoms in EG is replaced
by a nitrogen atom, i.e. ethanolamine (EA), the concentration of
G-ligand required to achieve spectral saturation are drastically
reduced (Figure 4). This effect is even more apparent when
ethylenediamine (EDA) is used where the affinity of the ligand
for Sm(II) is substantially increased in comparison to EG and EA
(
Figure 5).
400
500
l/ nm
600
700
0
0
M
0.002 M
0.012 M
0.004 M
0.014 M
0
.3
.008 M
Figure 2. The effect of (a) morpholine and (b) pyrrolidine on the spectrum of
SmI (2 mM).
2
0.2
0
.1
Pyrrolidine is of special importance since it is the aza analog of
THF. Its efficiency in coordinating to SmI is apparent from the
fact that ca. 0.1M of pyrrolidine is sufficient to displace the THF
from its complex with SmI and to reach saturation in the
2
0
400
500
600
700
2
l/ nm
spectrum despite the fact that the concentration of THF as a
solvent is two orders of magnitude higher (12.3 M). Overall,
these initial experiments demonstrate that a range of amines
have an exceptionally high affinity for Sm(II).
2
Figure 4. The effect of EA on the spectrum of SmI (2 mM).
Next, we examined G-ligands and there are significant
differences with alcohols and amines. In this case, a dioxygen
ligand such as ethylene glycol (EG) induces significant change
2
in the spectrum of SmI (Figure 3). This change in behavior is
likely due to an entropic effect since the enthalpy gained by the
formation of two Sm – O bonds is not over compensated by the
high entropic cost of a termolecular reaction required for
complexing two mono oxygen ligands.
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Figure 6. Normalized change in absorbance as a function of G-ligands
concentration (SmI 2 mM; NMEA = N-methylethanolamine).
2
0
0
0
M
.005 M
.008 M
0.002 M
0.006 M
0.01 M
0.004 M
0.007 M
0.4
0.3
0.2
0.1
0
It is important to note that in the analysis described above, we
are making the assumption that the spectral changes can be
correlated, at least semi quantitatively, with the degree of
complexation of the additives with Sm(II). To further support this
supposition, we developed competition experiments between the
G-ligands and HMPA, which is known to coordinate strongly to
Sm(II).[6b] In the exchange reaction shown in equation 1, the
equilibrium will be shifted to the right if the affinity of the G-ligand
(
2
G-L) to SmI is higher than that of HMPA.
400
500
600
700
l/ nm
The characteristic blue shift of the HMPA-Sm(II) complex can be
discerned from that of the other ligands and its disappearance
can be easily detected. To test this, the addition of EG to a
2
Figure 5. The effect of EDA on the spectrum of SmI (2 mM).
solution of SmI
Figure 7. The addition of a 10 fold excess of EG (based on
SmI ]) to the SmI -HMPA complex leads to moderate change in
the spectrum of SmI -HMPA. Nevertheless, the shape of newly
generated spectrum resembles SmI -HMPA, indicating that
HMPA has significantly higher affinity towards SmI over EG
under these conditions (Figure 7). At 20 mM of EA the observed
spectrum is intermediate between that of the two complexes
2
suggesting that the affinity to SmI of 20 mM of EA is similar to
2
containing HMPA was monitored as shown in
A noticeable feature in the spectrum for the G-ligands is the
change in the absorption position of the complexes in the visible
spectrum. While the newly formed absorption initiated by the
addition of EG is nearly centered between the two original peaks
[
2
2
2
2
2
of SmI (similar to MeOH and water), the nitrogen derivatives
2
induce a red shift. In the case of EA, the red shift remains
constant with continued addition of the additive. In contrast,
EDA induces an initial red shift but further addition induces a
blue shift with an absorption centered at approximately 500 nm.
This behavior is similar to HMPA which also induces a blue shift
in the spectrum of Sm(II).
Figure 6 contains the results described above in a more
quantitative manner. In this figure the total OD change to
saturation is normalized to 1 and the fraction of the change in
the O.D. is plotted as a function of the concentration of the G-
ligands. It is clear from this description that the order of reaching
complexation saturation is EDA>EA>EG. Another interesting
feature of the data is that the addition of a methyl group to EA
that of 8 mM HMPA to SmI
2
(see SI, Figure S5).
0.3
0.2
0.1
0
[EG]: 20 mM; [HMPA]: 8 mM
[EG]: 20 mM
[
HMPA]: 8 mM
(
N-methylethanolamine, NMEA) has a deleterious impact on the
affinity of the additive for Sm(II) (Figure S4). This is likely a
consequence of steric hindrance.
1.00
0.50
0.00
4
00
500
l/ nm
600
700
2
Figure 7. Ligand competition between HMPA and EG (SmI 2 mM).
EG
EA
D
Next we examined the addition of the higher affinity EDA to the
SmI -HMPA complex as shown in Figure 8. The presence of as
little as 8 mM EDA completely displaces the HMPA from Sm(II)
and the resulting spectrum is nearly indistinguishable from the
EDA
NMEA
2
2
spectrum of SmI containing EDA alone. Thus, the displacement
0
0.02
Additives]/ M
0.04
0.06
experiment clearly shows that as the number of nitrogen atoms
in the G-ligand atoms increases, the complexation ability is
enhanced.
[
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The equilibria discussed above provide the free energy of the
interaction between various amines and Sm(II). While the free
energy provides the overall driving force, it includes
contributions from enthalpy and entropy. The strength of an
interaction is best expressed by the enthalpy and we employed
calorimetry experiments to measure the relative affinities
between a set of ligands and Sm(II). Simple amines and
alcohols have complex stoichiometries, so we examined a crown
ether and related aza crowns since these have known, well-
defined interactions with metals including Sm(II).[9] The enthalpy
of interaction with 15-crown-5, aza-15-crown-5, and 4,10-diaza-
0.4
0.3
0.2
0.1
0
[
[
EDA]: 8 mM; [HMPA]: 8 mM
EDA]: 8 mM
[HMPA]: 8 mM
1
5-crown-5 were measured using isothermal titration calorimetry.
Figure S7 shows the data for these studies. Both 15-crown-5
and aza 15-crown-5 coordinate in a 2:1 stoichiometry with SmI
and the interaction with the aza crown is more exothermic. The
,10-diaza-15-crown-5 coordinates to Sm(II) in 1:1
2
400
500
l/ nm
600
700
4
a
stoichiometry, but the interaction is significantly more exothermic.
Since initial part of an isotherm indicates the enthalpy change
associated with a complexation process, we have performed ITC
Figure 8. Ligand competition between HMPA and EDA (SmI
2
2 mM).
3
2
titration of 10 mM of SmI with 10 mM of above mentioned three
To this point, we have only considered ligation by sp hybridized
atoms. Another question is whether this dominance of nitrogen
crown ethers by adding 5 L of aliquot each time (see SI, Figure
S8). This experiment allows us to have a more accurate
measurement of enthalpy change associated with complexation
2
over oxygen also prevails in sp hybridization. Unfortunately, the
high reactivity of imines with SmI
measurement. A preliminary competition experiment between
THF and p-methoxypyridine (the latter reacts with SmI but at a
2
prevents an easy spectral
of SmI
2
and crown ethers (Table 1). As anticipated,
complexation phenomenon is more exothermic when more
number of nitrogen atom is incorporated in crown ether.
2
rate slow enough to enable the recording of its spectrum)
showed that it markedly affects the spectrum, however, it takes
about 0.4 M in order to reach saturation in the spectrum (Figure
2
Table 1: DH of complexation between SmI and crown ethers
Crown ethers
5-crown-5
Aza-15-cown-5
,10-diaza-15-crown-5
DH (kcal/mol)
2
S6). A better comparison between the sp ligands should be
performed with an sp2 hybridized oxygen rather than the sp3
oxygen of THF. Because of the high reactivity of imines, the
comparison was achieved through kinetic experiments. In the
1
-11.7±0.1
-18.4±0.3
-20.0±0.5
reaction of SmI
2
(2 mM), with benzophenone imine (10 mM), the
4
SmI vanished in nearly the dead time of the instrument (<3
2
msec) whereas the reduction of benzophenone (10 mM) was
about 30 times slower (Figure 9). Yet the reduction potential of
benzophenone imine is much smaller than that of
Overall, these data demonstrate that the replacement of an
oxygen with a nitrogen in the crown ligands leads to a more
exothermic interaction with Sm providing further evidence that
nitrogen containing ligands have a higher affinity for the metal
than oxygen.
[8]
benzophenone itself, suggesting that the enhanced reactivity
with the imine is due to its stronger binding to the sp2
of SmI
2
hybridized nitrogen.
0
.08
.04
0
The discussion up to this point has dealt with the ability of the
Benzophenone
Benzophenone imine
+
2
ligands to coordinate to Sm . Yet, the interaction of these
ligands with Sm+3 is very important because the relative strength
of these interactions governs the equilibrium of equation 2 and
2
therefore impact the reduction potential of SmI .
0
Since the solubility of Sm+3 in THF is low and it does not have a
significant absorption in the UV – VIS range, we measured the
+
3
interactions of the G-ligands with Sm indirectly by measuring
the ability of Sm+3 to pull away G-ligands from their complex with
Sm+2 (equation 3).
0.00
0.05
time/ sec
0.10
Figure 9. kinetic traces for the reaction of SmI
2
with benzophenone and
benzophenone imine.
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Since SmI
Sm+3 to a solution containing a complex of a G-ligand and SmI
will strip off the ligand generating free SmI . The appearance of
will indicate that the G-
2
has a well-defined visible absorption, the addition of
(a)
2
2
SmI2
SmI2 + EA + SmI3
SmI2 + EA
0.3
0.2
0.1
0
the characteristic absorption of SmI
2
ligands bind more strongly to Sm+3 than to Sm+2.
This strategy is exemplified below for HMPA, an additive that
decreases the reduction potential of SmI
powerful reductant) because it binds more firmly to Sm than to
2
(making it a more
+
3
+
2 [6b, 10]
Sm .
ligand stabilizes the higher oxidation state of Sm. Figure 10
shows the spectrum of SmI (2 mM), after adding 4 mM HMPA.
Addition of SmI (2 mM) sequesters HMPA bound to SmI and
To put it simply, the presence of the strong donor
2
3
2
as a result, the original spectrum of SmI
2
is restored.
400
500
600
700
l/ nm
SmI2
SmI2+HMPA+SmI3
SmI2+HMPA
(b)
0.3
0.2
0.1
0
0.3
0.2
0.1
0
SmI2
SmI2+Pyrrolidine
SmI2+pyrrolidine+SmI3
400
500
l/ nm
600
700
400
500
l/ nm
600
700
Figure 10. Spectrum regeneration showing the higher affinity of HMPA to
Sm+3
.
Figure 11. (a) Spectra of, SmI
Spectra of, SmI
(2 mM); + pyrrolidine (2 mM); +Sm+3 (2 mM).
(2 mM); + EA (8 mM); +Sm+3 (2 mM). (b)
2
2
We next carried out the same experiment using EG.
Complexation to EG does not affect the spectrum to nearly the
same degree as HMPA but nevertheless, some restoration of
the could be discerned (Figure S9).
Since the relative strength of the interaction of the ligands with
Sm+3 and Sm+2 is known to effect the reduction potential of SmI2,
When the nitrogen analog EDA was used, it formed a precipitate
+
3
the impact of NMEA and EG on the reduction potential of SmI
was determined using cyclic voltammetry. Depicted in Table 2
are the reduction potentials of SmI as a function of the
2
with Sm , thus masking the results for this G-ligand (Figure
S10). However, very good results were obtained with EA and
pyrrolidine (Figure 11). These results imply that nitrogen-based
ligands have a higher affinity than oxygen containing ligands for
2
concentration of, EG, NMEA and N, N’-dimethylethylenediamine
(NN’DMEDA). The latter two were chosen because at high
concentration, EA and EDA precipitates with the generated Sm+3
interfering with the measurements. Once again, HMPA data is
provided as a benchmark.
+
3
Sm .
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-
1.2
Table 2. Oxidation Peak potential as a function of concentration
CV
0
.19
HMPA[a]
EG[a]
NMEA[a]
NN’DMEDA[a]
UV
Conc. M
0
-1.13
-1.59
-1.73
-1.13
-1.13
-1.41
-1.6
-1.13
-1.4
-1.6
0
0
0
0
0
0
0
0
0
0
0
.004
.008
.01
-1.51
-
2
0.09
0.05
-1.35
0
0.025
NMEA]/ M
.012
.016
.02
-1.69
-1.74
-1.77
-1.83
-1.56
-1.57
-1.59
-1.6
[
-1.84
2
Figure 12. Reduction potential and O.D. of NMEA-SmI complexes as a
-1.43
-1.5
function of concentration.
.024
.03
performed in the presence of HMPA/TFE for comparison
purpose. TFE was used as source of proton in HMPA reaction,
since it is known for non-coordinating nature and hence will not
.032
.04
-1.84
-1.85
2
disrupt the SmI -HMPA complex. Yield of the reactions are
-1.52
-1.52
tabulated in Table 3. Substrate 1 and 2 were reduced to their
corresponding alcohols whereas 3 and 4 were reduced to their
dihyro product.
.05
[
2
a]: [SmI ]: 2 mM
The data show that HMPA and NMEA reach nearly the same
reduction potential although with NMEA, larger concentration of
the ligands are necessary, consistent with spectral
measurements showing that it has a lower affinity for Sm. EG
with its two oxygen atoms has a more modest impact on the
redox potential.
Equation 2 is relevant not only to the reduction potential of the
complexes, but also to the electronic excitation since in the
excited state, where the electron is distanced from the nucleus
Chart 1. Substrates used for this study
+
3
somewhat resembling Sm . Figures 12 (NMEA) and S11 (EG)
show that indeed, there is some similarity between the CV data
and spectroscopic results. However, bearing in mind that we
monitor the change in the OD which is related to the absorption
coefficient rather than to the wavelength which corresponds to
excitation energy, it is our supposition that the correlation
reflects the degree of complexation and indirectly the strength of
complexation.
Table 3. Yield of reductions with NMEA[a], NN’DMEDA[a] and HMPA/TFE[a] as
additives.
Substrates
Yield NMEA
Yield NN’DMEDA
Yield HMPA/TFE
1
2
3
4
97[b]
0[c]
99[c]
CV data tabulated in Table 2 also suggests that nitrogen
containing G-ligands can potentially be employed to carry out
reductions of substrates which are recalcitrant towards reduction
98[b]
17[c]
99[c]
95[b]
50[c]
18[c]
0[c]
99[c]
0[c]
by SmI
supposition, the reduction of several substrates shown in Chart
were examined. Initial reductions were carried out on
cyclohexylmethyl ketone (1), 4-phenyl-2-butanone (2)
2
when no additives are present. To examine this
1
[
[
a] [SmI
2
]: 0.1 M; [Subs]: 0.046 M; [NMEA]: 0.4 M; [NN’DMEDA]: 0.4 M;
anthracene (3) and phenanthrene (4) as model substrates in the
HMPA]: 0.4 M and [TFE]: 0.4 M; [b] instantaneous decolorization; [c] reaction
presence of NMEA and NN’DMEDA. These reactions were also
time 2 hr.
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Data presented in Table 3 clearly indicates that NMEA is very
water significantly changes the shape of SmI
enthalpy of complexation for water and Et N measured through
ITC experiments was found to be comparable (-2.5 kcal/mole for
water and -3.3 kcal/mole for Et N). It was shown previously that
introduction of alkyl group one oxygen has significant deleterious
impact on the coordinating ability.[3j, 4c] We have also seen
similar phenomenon when a methyl group was added on the
nitrogen of ethanolamine (Figure 6). Based on these findings it is
our supposition that water forms much stronger complex than
spectrum.[13b] The
2
potent additive to mediated reductions by SmI
2
. On the other
3
hand, the reactions with NN’DMEDA were sluggish and resulted
poor yields. This could be due to lack of acidic protons which are
important for these reductions.[3h-j] It is also important to note that
phenanthrene which was not reduced by the HMPA/TFE
system, can be reduced up to 50% in the presence of NMEA.
Since the additive HMPA is a suspected carcinogen, these initial
experiments show that NMEA may be a potential alternative. To
determine whether NMEA is indeed potent towards reduction of
range of substrates, reduction of methyl benzoate (5), 4-n-
butylbenzamide (6) and trans-stilbene (7) was carried out. In all
cases, good to excellent yields were obtained (Table 4). It is
interesting to note that reduction of 4-n-butylbenzamide resulted
alcohol exclusively. These initial results show that amines are
3
3 2 3
Et N and hence despite of azaphilicity of SmI , using Et N
should not have any impact on the key feature of proposed
mechanisms where Sm bound water is deprotonated by amine.
Nevertheless, amines such as piperidine and pyrrolidine may
effectively compete with water coordination and hence choosing
right concentration of water and amine may be vital in these
cases.
not only good ligands for SmI
2
, but they are potential additives
for reductions mediated by SmI
2
.
2
Table 4. Yield of SmI /NMEA mediated reductions.
Conclusions
Substrate
Product
Yield
%)
(
Using several diagnostic tools we have demonstrated that under
5
6
7
benzyl alcohol
4-n-butylbenzyl alcohol
bibenzyl
99[b]
similar conditions, nitrogen coordinates to SmI
oxygen. This is demonstrated for sp atoms in cyclic and acyclic
2
stronger than
3
99[b]
2
ligands (n-BuNH vs. n-BuOH and THF vs. pyrollidine), bidentate
99[b]
ligands (ethylene glycol vs ethanolamine and ethylenediamine),
crown ethers (15-crown-5 vs Aza-15-crown-5 and 4,10-diaza-15-
2
[
a] [SmI
2
]: 0.1 M; [Subs]: 0.046 M; [NMEA]: 0.4 M [b] instantaneous
crown-5) as well as for sp hybridized atoms (imine vs. carbonyl).
decolorization
This difference in affinity is even more pronounced for Sm+3
resulting in a stronger effect of the aza ligands on the reduction
potential of SmI
nitrogen ligand coordination on the reactivity and selectivity of
SmI -based reductions and the results of this work will be
2
.
We are currently examining the impact of
2
Finally, it is important to consider whether azaphlicity of SmI will
have any impact on SmI
2
reductions in the presence of
2
water/amine. Mixtures of water/amine have proven to be one of
most efficient and potent additives to carry out reductions of a
range of substrates.[11] Hilmersson and others carried out
seminal work in this area increasing the substrate scope of this
additive.[11b-h] The scope of this additive was further improved by
Procter and Szostak who demonstrated that substrates such as
reported in due course.
Experimental Section
carboxylic acid derivatives typically recalcitrant to electron
/water/amine.[
12]
General: All the reagents were purified prior to their use by following
standard procedures. The liquid reagents were distilled under argon and
degassed with argon prior to use. The THF was dried and freshly distilled
transfer can be reduced by SmI
2
Several
mechanistic scenarios have been proposed for the reagent
combination.[12f, 13] The common theme among the different
mechanistic scenarios is the proposal that water coordinates to
off sodium/benzophenone under an argon atmosphere. The SmI
2
was
freshly prepared prior to use by stirring samarium metal and 1,2-
SmI
findings described here, the question is: Can an amine replace
water from the coordination shere of SmI Although different
amines can be used in the SmI /water/amine system, Et N is the
most commonly used amine, hence we have tried to address
whether Et N can displace water bound to SmI . The ideal
experiment in this case would be ligand exchange experiment,
similar to HMPA/G-liagnds system. However, instability of SmI
in the presence of water and Et N prohibits the performance of
this measurement. UV-visible spectra study in the presence of
Et N (0.05 M-0.5 M) shows no change in the shape of SmI
spectrum (Figure S12). It known that under similar condition,
2
and amine deprotonates the ligated water. In light of the
diiodoethane at room temperature. The concentration of SmI
determined by UV-visible spectroscopic measurements (l 619 nm;
2
was
=
2
?
635). The spectral, cyclic voltammetric, caloriemetric titration and kinetic
experiments were carried out in clean and dry glassware under a
nitrogen atmosphere.
2
3
3
2
Cyclic Voltammetry: Cyclic voltammetry was performed in a single
potentiostat from Bio Logic Scientific Instruments. Glassy carbon,
Ag/AgNO in acetonitrile and Pt wire were used as working, reference
3
and counter electrode, respectively. The glassy carbon electrode was
polished with polishing alumina and then washed thoroughly before each
sets of measurements. The reference electrode had a potential of 0.542
V with respect to SHE. Tetrabutylammonium hexafluorophosphate (0.1
2
3
3
2
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Chemistry - A European Journal
10.1002/chem.201703394
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M) was used as a supporting electrolyte. The SmI
mM for all set of experiments.
2
concentration was 2
SH thanks Israel Science Foundation for supporting this work at
Bar-Ilan University. RAF is grateful to the National Science
Foundation (CHE 1565741) for support of the work at Lehigh
University.
Isothermal Titration Calorimetry: ITC measurements were carried in
MicroCal Calorimetry instruments. In a typical experiment, SmI (10 mM)
2
solutions in acetonitrile are taken inside cell of instrument and 200 mM
solution of ligands are injected (5 L/injection) from pipettes. The ligands
concentrations for determining DH of complexation was 10 mM. Enthalpy
change upon addition of ligands to metal ions was plotted against molar
ratio.
Keywords: N ligands • chelates • samarium • amines • affinity
[
1]
a) J. L. Namy, P. Girad, H. B. Kagan, New J. Chem. 1977, 1, 5–7; b) P.
Girard, J. L. Namy, H. B. Kagan, J. Am. Chem. Soc. 1980, 102, 2693–
UV-visible Spectral Measurements: Spectral measurements were
performed with a Stopped Flow Spectrometer. To record the spectra of
2698; c) G. A. Molander, C. R. Harris, Chem. Rev. 1996, 96, 307 – 338;
2 2
SmI in the presence of different concentrations of additives, SmI and
corresponding additive were taken in two different syringes and mixed
with stopped flow machine and wavelength was scanned over a range to
d) G. A. Molander, C. R. Harris, Tetrahedron 1998, 54, 3321–3354; e)
A. Krief, A. –M. Laval, Chem. Rev. 1999, 99, 745–777; f) P.G. Steel, J.
Chem. Soc. Perkin Trans. 1 2001, 2727–2751; g) D. J. Edmonds, D.
Johnston, D. J. Procter, Chem. Rev. 2004, 104, 3371–3403; h) M.
Szostak, M. Spain, D. J. Procter, Chem. Soc. Rev. 2013, 42, 9155–
obtain the spectrum. The concentration of SmI
was 2 mM.
2
in all the experiments
9183; i) M. Szostak, N. J. Fazakerley, D. Parmar, D. J. Procter, Chem.
Ligand exchange reactions: Two kinds of ligand exchange experiments
were performed. In one type of experiment we studied displacement of
Rev. 2014, 114, 5959-6039; j) X. Just-Baringo, D. J. Procter, Acc.
Chem. Res. 2015, 48, 1263–1275; k) D. J. Procter, R. A. Flowers II, T.
Skrydstrup, Organic Synthesis using Samarium Diiodide: A Practical
Guide, Royal Society of Chemistry Publishing, UK, 2010; l) T. V. Chciuk,
R. A. Flowers, II Role of Solvents and Additives in Reactions of Sm(II)
Iodide and Related Reductants. In Science of Synthesis Knowledge
Updates Marek, I. Ed.; Thieme: Stuttgart, 2016; Vol. 2, pp. 171.
a) A. Dahlén, G. Hilmersson, Eur. J. Inorg. Chem. 2004, 3393−3403; b)
R. A. Flowers II, Synlett. 2008, 10, 1427-1439.
HMPA, complexed to SmI
2
, by other ligands such as ethylene glycol. In
these experiment, SmI -HMPA complex was taken in one syringe and
2
ligands of interest was added to another syringe and they were mixed
with the stopped flow instrument followed by wavelength scan to record
the spectrum of system. A series of experiments were conducted with
changing the ligand concentration with fixed SmI
observe the displacement of HMPA with ligand of interest. The
concentration of SmI and HMPA for all the experiments were 2 mM and
mM respectively.
2
/HMPA concentration to
[2]
[3]
2
a) P. R. Chopade, E. Prasad, R. A. Flowers II, J. Am. Chem. Soc. 2004,
126, 44-45; b) M. Amiel-Levy, S. Hoz, J. Am. Chem. Soc. 2009, 131,
8
8280-8284; c) D. Parmar, L. A. Duffy, D. V. Sadasivam, H. Matsubara,
P. A. Bradley, R. A. Flowers II, D. J. Procter, J. Am. Chem. Soc. 2009,
131, 15467-15473; d) M. Szostak, M. Spain, K. A. Choquette, R. A.
Flowers II, D. J. Procter, J. Am. Chem. Soc. 2013, 135, 15702-15705;
e) M. Szostak, M. Spain, D. J. Procter, J. Am. Chem. Soc. 2014, 136,
In another type of experiment, we have determined relative affinity of a
ligand towards Sm2+ vs Sm3+. In this experiment, SmI
and SmI was
taken together in one syringe and another syringe was filled with ligand
of interest. Two different solutions were mixed through stopped flow
instrument followed by scan of wavelength to record the spectrum. The
2
3
8459-8466; f) M. Szostak, M. Spain, B. Sautier, D. J. Procter, Org. Lett.
2014, 16, 5694-5697; g) M. Szostak, M. Spain, D. J. Procter, J. Org.
spectrum was compared to the spectrum of SmI
2
and SmI
2
with that
Chem. 2014, 79, 2522-2537; h) T. V. Chciuk, R. A. Flowers II, J. Am.
Chem. Soc. 2015, 137, 11526-11531; i) T. V. Chciuk, W. R. Anderson,
R. A. Flowers II, J. Am. Chem. Soc. 2016, 138, 8738-8741; j) T. V.
Chicuk, W. R. Anderson, R. A. Flowers II, Angew. Chem. Int. Ed. 2016,
ligand. The concentration of SmI
was 2 mM.
2
as well as SmI for all the experiments
3
Kinetics: Stopped flow kinetic measurements were performed with a
Stopped Flow Spectrometer. The reactions were performed under
pseudo-first-order condition (SmI : 2 mM; substrates: 10 mM). The rates
2
of reactions were monitored by following the disappearance of the SmI
absorbance at 660 nm.
55, 6033-6036; k) T. V. Chciuk, A. M. Li, A. Vazquez-Lopez, W. R.
Anderson, Jr., R. A. Flowers II, Org. Lett. 2017, 19, 290-293.
[
[
[
4]
5]
6]
a) R. J. Enemærke, K. Daasbjerg, T. Skrydstrup, Chem. Commun.
2
1
999, 343-344; b) R. S. Miller, J. M. Sealy, M. Shabangi, M. L.
Kuhlman, J. R. Fuchs, R. A. Flowers II, J. Am. Chem. Soc. 2000,
22, 7718-7722; c) J. A. Teprovich Jr., M. N. Balili, T. Pintauer, R. A.
1
Preparative reaction: In a typical procedure, to a 5 mL of 0.1 M of SmI
2
,
Flowers II, Angew. Chem. Int. Ed. 2007, 46, 8160-8163; d) H.
Farran, S. Hoz, Org. Lett. 2008, 10, 4875-4877; e) D. V. Sadasivam, J.
A. Teprovich Jr., D. J. Procter, R. A. Flowers II, Org. Lett. 2010, 12,
0.23 mmole of substrate [cyclohexylmethyl ketone (0.029 g), 4-phenyl-2-
butanone (0.034 g), anthracene (0.041 g), phenanthrene (0.041), methyl
benzoate (0.015 g), 4-n-butylbenzamide (0.02 g) and trans-stilbene
4
140-4143.
a) W. J. Evans, D. K. Drummond, H. Zhang, J. Atwood, Inorg. Chem.
998, 27, 575-579; b) E. Prasad, B. W. Knettle, R. A. Flowers II, J. Am.
(
0.041 g)] and 2 mmole of N-methylethanolamine (0.15 g) was added.
Reaction quenched by passing air through solution. The reaction mixture
was diluted with 30 mL of dichloromethane and treated with 20 mL of 0.1
1
Chem. Soc. 2002, 124, 14663-14667; c) M. Janjetovic, A. M. Träff, T.
Anker, J. Wettergreen, G. Hilmersson, Chem. Commum. 2013, 49,
M
HCl. The aquous layer was further washed with 2x20 mL of
dichloromethane. The organic layer was washed with braine solution,
dried over MgSO4 and concentrated under reduced pressure. The crude
product was analyzed with NMR to get the yield of reaction. In each case
the weight of crude material was measured to make sure 90 % or above
organic material was recovered.
1826-1828; d) T. V. Chciuk, G. Hilmersson, R. A. Flowers II, J. Org.
Chem. 2014, 79, 9441-9443; e) I. V. Basalov, O. S. Yurova, A. V.
Cherkasov, G. K. Fukin, A. A. Trifonov, Inor. Chem. 2016, 55, 1236-
1244.
a) A. Yacovan, S. Hoz, I. Bilkis, J. Am. Chem. Soc. 1996, 118, 261-262;
b) J. B. Shotwell, J. M. Sealy, R. A. Flowers II, J. Org. Chem. 1999, 64,
5251-5255; c) E. Prasad, R. A. Flowers II, J. Am. Chem. Soc. 2005,
127, 18093-18099.
Acknowledgements
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Chemistry - A European Journal
10.1002/chem.201703394
FULL PAPER
[
7]
a) T. V. Chciuk, B. P. Boland, R. A. Flowers II, Tetrahedron Lett. 2015,
Hilmersson, Chem. Eur. J. 2003, 9, 1123-1128. (f) A. Dahlén, G.
Hilmersson, B. W. Knettle, R. A. Flowers II, J. Org. Chem. 2003, 68,
4870-4875. (g) A. Dahlén, A. Sundgren, M. Lahmann, S. Oscarson, G.
Hilmersson, Org. Lett. 2003, 5, 4085-4088; h) T. A. Davis, P. R.
Chopade, G. Hilmersson, R. A. Flowers II, Org. Lett. 2005, 7, 119-122.
[12] (a) M. Szostak, M. Spain, D. J. Procter, Org. Lett. 2012, 14, 840-843.
(b) M. Szostak, M. Spain, D. J. Procter, Org. Lett. 2014, 16, 5052-5055.
(c) M. Szostak, B. Sautier, M. Spain, D. J. Procter, Org. Lett. 2014, 16,
1092-1095. (d) M. Szostak, M. Spain, A. J. Eberhart, D. J. Procter, J.
Am. Chem. Soc. 2014, 136, 2268-2271. (e) M. Szostak, M. Spain, A. J.
Eberhart, D. J. Procter, J. Org. Chem. 2014, 79, 11988-12003. (f) M.
Szostak, M. Spain, D. J. Procter, Chem. Eur. J. 2014, 20, 4222-4226.
(g) S. R. Huq, S. Shi, M. Szostak, J. Org. Chem. 2017, 82, 6528-6540.
[13] a) A. Dahlén, G. Hilmersson, J. Am. Chem. Soc. 2005, 127, 8340-8347;
b) S. Maity, S. Hoz. Chem. Eur. J. 2015, 21, 18394-18400.
56, 3212-3215; b) S. Maity, S. Hoz, ChemistrySelect 2017, 2, 2499-
2502.
[
8]
9]
a) S. Zhan, M. D. Hawley, J. Electroanal. Chem. 1991, 319, 275-290; b)
N. G. Tsierkezos, J. Solutions Chem. 2007, 36, 1301-1310.
[
a) C. J. Pederson, J. Am. Chem. Soc. 1967, 89, 7017-7037; b) C. J.
Pederson, J. Am. Chem. Soc. 1976, 89, 2495-2496; c) J. A. Teprovich,
Jr., E. Prasad, R. A. Flowers II, Angew. Chem. Int. Ed. 2007, 46, 1145-
1
148.
10] a) M. Shabangi, R. A. Flowers II, Tetrahedron Lett. 1997, 38,
137−1140; b) R. J. Enemærke, T. Hertz, T. Skrydstrup, K. Daasbjerg,
Chem. Eur. J. 2000, 6, 3747-3754; c) S. Halder, S. Hoz, J. Org. Chem.
014, 79, 2682-2687.
[
[
1
2
11] a) W. Cabri, I. Candiani, M. Colombo, L. Franzoi, A. Bedeschi,
Tetrahedron Lett. 1995, 36, 949-952; b) A. Dahlén, G. Hilmersson,
Tetrahedron Lett. 2002, 43, 7197-7200. (c) A. Dahlén, G. Hilmersson,
Tetrahedron Lett. 2003, 44, 2661-2664. (d) A. Dahlén, A. Petersson, G.
Hilmersson, Org. Biomol. Chem. 2003, 1, 2423-2426. (e) A. Dahlén, G.
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Entry for the Table of Contents
FULL PAPER
In spite of the prevalence ligands that
S. Maity, R. A. Flowers II,* S. Hoz*
2
coordinate to SmI through oxygen in
synthesis, experimental results
demonstrate that nitrogen-based
ligands have a significantly higher
affinity for the reagent and provide a
powerful reducing system.
Page No. – Page No.
Aza vs.Oxophilicity of SmI
of a Paradigm
2
: A Break
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