Preparation of samarium(II) iodide: Quantitative evaluation of the effect of water, oxygen, and peroxide content, preparative methods, and the activation of samarium metal

Article abstract of DOI:10.1021/jo300135v

Samarium(II) iodide (SmI₂) is one of the most important reducing agents in organic synthesis. Synthetic chemistry promoted by SmI₂ depends on the efficient and reliable preparation of the reagent. Unfortunately, users can experience difficulties preparing the reagent, and this has prevented realization of the full synthetic potential of SmI₂. To provide synthetic chemists with general and reliable methods for the preparation of SmI₂, a systematic evaluation of the factors involved in its synthesis has been carried out. Our studies confirm that SmI₂ is a user-friendly reagent. Factors such as water, oxygen, and peroxide content in THF have little influence on the synthesis of SmI₂. In addition, the use of specialized glovebox equipment or Schlenk techniques is not required for the preparation of SmI₂. However, our studies suggest that the quality of samarium metal is an important factor and that the use of low quality metal is the main cause of failed preparations of the reagent. Accordingly, we report a straightforward method for activation of "inactive" samarium metal and demonstrate the broad utility of this protocol through the electron transfer reductions of a range of substrates using SmI₂ prepared from otherwise "inactive" metal. An investigation into the stability of SmI₂ solutions and an evaluation of commercially available solutions of the reagent is also reported.

Full text of DOI:10.1021/jo300135v

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pubs.acs.org/joc
Preparation of Samarium(II) Iodide: Quantitative Evaluation of the
Effect of Water, Oxygen, and Peroxide Content, Preparative
Methods, and the Activation of Samarium Metal
Michal Szostak, Malcolm Spain, and David J. Procter*
School of Chemistry, University of Manchester, Oxford Road, Manchester, M13 9PL, United Kingdom
S
* Supporting Information
ABSTRACT: Samarium(II) iodide (SmI2) is one of the most important
reducing agents in organic synthesis. Synthetic chemistry promoted by
SmI2 depends on the efficient and reliable preparation of the reagent.
Unfortunately, users can experience difficulties preparing the reagent,
and this has prevented realization of the full synthetic potential of SmI2.
To provide synthetic chemists with general and reliable methods for the
preparation of SmI2, a systematic evaluation of the factors involved in its
synthesis has been carried out. Our studies confirm that SmI2 is a user-
friendly reagent. Factors such as water, oxygen, and peroxide content in THF have little influence on the synthesis of SmI2. In
addition, the use of specialized glovebox equipment or Schlenk techniques is not required for the preparation of SmI2. However,
our studies suggest that the quality of samarium metal is an important factor and that the use of low quality metal is the main
cause of failed preparations of the reagent. Accordingly, we report a straightforward method for activation of “inactive” samarium
metal and demonstrate the broad utility of this protocol through the electron transfer reductions of a range of substrates using
SmI2 prepared from otherwise “inactive” metal. An investigation into the stability of SmI2 solutions and an evaluation of
commercially available solutions of the reagent is also reported.
Scheme 1. Synthesis of SmI2 Using 1,2-Diiodoethane
(Kagan’s Method) and Iodine (Imamoto’s Method)
INTRODUCTION
■
Samarium(II) iodide (SmI2) is one of the most important
reducing agents available in the laboratory. Since its
introduction to synthetic chemistry by Kagan in 1977,1
functional group transformations and C−C bond-forming
reactions mediated by SmI2 have ranked among the most
useful tools available to organic chemists.2 These processes
proceed through either one-electron or two-electron pathways
or sequences involving both modes of activation and have been
extensively used in new synthetic strategies, natural product
synthesis, and cascade reactions.3,4 Many SmI2-mediated
transformations proceed with exquisite control of structure
and stereochemistry to furnish bond disconnections impossible
to achieve with other reagents. An important feature of SmI2 is
the ability to tune its properties through the use of appropriate
additives.5,6 However, to fully exploit the versatility of SmI2,
laboratories involved in synthetic chemistry require efficient
and reliable methods for its preparation.
As first reported by Kagan, SmI2 can be conveniently
prepared by the reaction of samarium metal with 1,2-
diiodoethane in THF (Scheme 1).1 This procedure is typically
carried out using carefully dried and deoxygenated solvents and
strict Schlenk or glovebox techniques. Several years after
Kagan’s seminal work, Imamoto described a more atom-
economical method for the synthesis of SmI2 using samarium
metal and iodine as the oxidant in refluxing THF (Scheme 1).7
However, the detailed mechanism for the formation of SmI2
using this method has not been elucidated. The methods of
Kagan and Imamoto are the two most common protocols used
for the preparation of SmI2 for organic chemistry applications.
Several other methods for the preparation of SmI2 have been
reported and are shown in Scheme 2. Kagan reported the use of
diiodobutane or diiodomethane as oxidants (the latter method
was subsequently popularized in elegant studies by Molander);8
Ishii described the preparation of a SmI2 equivalent from
samarium metal, TMSCl and NaI;9 Concellon
found that
́
sonication of samarium metal and iodoform at room temper-
ature gave SmI2 in THF after short reaction times;10 Flowers
utilized high intensity ultrasound to synthesize SmI2 from
samarium metal and iodine in a wide range of solvents;11 and
finally, Hilmersson reported a rapid synthesis of SmI2 using
iodine and microwave heating.12 These new procedures have
yet to experience the widespread take-up associated with the
original Kagan and Imamoto methods.13 The development of
Received: February 1, 2012
Published: February 29, 2012
© 2012 American Chemical Society
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and in light of contrasting literature evidence regarding the
preparation of SmI2, we began a systematic investigation of the
potential factors affecting the preparation of SmI2. For our
study, we selected Kagan’s method using 1,2-diiodoethane1 and
Imamoto’s method using iodine7 as the two most practical and
most commonly utilized methods for the preparation of SmI2.
The formation of the reagent was followed by titration using
the method developed by Hilmersson12 and by standard
iodometric titration.11 However, Hilmersson’s method is most
informative as it measures only the amount of active Sm(II)
reagent. Since during the last 15 years we have noted that the
quality of samarium metal can dramatically affect the efficiency
of synthesis of SmI2 (in extreme cases, some batches of
commercial samarium metal failed to provide SmI2), we
therefore investigated different methods for the activation of
samarium metal and its use for the synthesis of SmI2.
Scheme 2. Additional Procedures for the Synthesis of SmI2
Herein we report the accumulation of sufficient experimental
data to allow us to dispel several myths surrounding the reagent
and to report practical, robust and reliable protocols for the
preparation of SmI2 for use by the synthetic chemistry
community.
new methods for the preparation of SmI2 by groups working in
the area suggests that a “foolproof” protocol for the synthesis of
the reagent is not yet available.
Traditionally, care is taken to use absolutely dry solvents, an
oxygen-free atmosphere, and good quality samarium metal
when preparing SmI2 using Kagan's and Imamoto's meth-
ods.14−17 Relatively expensive solvent drying columns and
highly reactive metals have been typically employed to dry THF
for use in the preparation of SmI2,16 and the careful
deoxygenation of solvents means that significant effort has
been devoted to the preparation of the reagent.17 The quality of
samarium metal from commercial suppliers may vary on a batch
to batch basis, and glovebox systems are often used to store
samarium metal and/or to prepare the reagent.15
Although various techniques for activating samarium metal
have been described, a quantitative study of their efficacy has
not been described.18 Reports describing the negative influence
of peroxide content in THF on the formation and stability of
SmI2 have also been published.19 A survey of the literature
reveals many examples in which the yields of SmI2-mediated
reactions are likely compromised due to low quality reagent
that in turn arises from a poor understanding of the factors
governing the synthesis of SmI2.20 Clearly, difficulties in
preparing SmI2 hinder the spread of its use in synthesis and
perpetuate the myth that the reagent is difficult to work with.
Furthermore, the need for a “foolproof” protocol for the
synthesis of SmI2 in THF is underlined by the fact that the
preparation of SmI2 in solvents other than THF has met with
limited success despite considerable efforts devoted toward this
goal.21 Factors that hinder the use of SmI2 in solvents other
than THF include less predictable solution properties that can
lead to limited substrate and/or reaction scope. In addition,
although solutions of SmI2 in THF are available from
commercial suppliers it is often noted that the stability and
quality of the commercial reagent is variable and its use
problematic.22 Finally, since SmI2 is used for the preparation of
other Sm(II)-based reagents, the requirement for a reliable
preparation of the reagent reaches beyond the chemistry of
SmI2 alone.23
RESULTS AND DISCUSSION
■
For our study, we selected water, oxygen, and peroxide content,
the quality of samarium metal, and the preparation procedure
as the most likely factors affecting the formation of SmI2.15−20
We started our investigation by studying in detail the synthesis
of SmI2 using Kagan’s method employing 1,2-diiodoethane as
the oxidant.
For comparison, all reactions were run for the same period of
time, with runs typically performed in parallel to facilitate the
identification of key factors influencing the synthesis of SmI2.
To impart reasonable stability on the resultant SmI2 solutions,
and following Kagan’s seminal report,1 a 2-fold excess of
samarium metal was typically used relative to the oxidant. In all
cases, in addition to the concentration of the active Sm(II)
species, the induction timethat is, the time after which the
solution turned bluewas noted. However, it should be noted
that the blue color of the reaction mixture does not indicate
that the synthesis of SmI2 is complete.15−20 For example, we
have found that blue solutions of SmI2 in THF with
concentrations lower than 0.005 M are visually indistinguish-
able from saturated solutions of 0.1 M in THF, which
corresponds to at least a 20-fold difference in molarity.
All runs were performed on two preparative scales (5.5 and
16.5 mmol with respect to the oxidant), solutions of SmI2 were
allowed to settle for at least 30 min prior to titration to ensure
homogeneous solutions, and titration was performed in
triplicate. For the synthesis of SmI2 using 1,2-diiodoethane,
the oxidant was freshly purified by washing with sodium
thiosulfate prior to each preparation of the reagent and stored
in the absence of light prior to use. In contrast to literature
reports,15b,20h we found that 1,2-diiodoethane is relatively stable
when purified and stored under inert atmosphere in the
absence of light (<5% decomposition after 24 h at room
1
temperature as determined by H NMR analysis). To aid in
Our laboratory has been at the forefront of developing
reactions promoted by SmI2.24 In our recent studies on
reactions mediated by the SmI2−H2O complex,24e,25 we
required a method of preparation that would reliably provide
reagent solutions with sufficient low-valent lanthanide purity for
mechanistic and rate studies. As the reports of Kagan and
Imamoto did not give the information needed for our studies,
identifying key factors affecting the synthesis of SmI2, the same
batch of samarium metal, solvent and oxidant was typically used
for the preparation of SmI2 under a specific set of conditions. It
should be noted that the reaction of samarium metal and 1,2-
diiodoethane initially gives SmI2. However, in the presence of a
large excess of 1,2-diiodoethane, the initially formed SmI2 is
oxidized to SmI3, which is subsequently reduced to SmI2 by
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samarium metal (Scheme 3).26 These changes in the oxidation
state of samarium can be followed by the color changes of the
reaction mixture.
THF.30 For comparison, three other batches of THF were also
used. All reactions were carried out using literature conditions
for the synthesis of SmI2: carefully degassed THF, standard
Schlenk techniques and samarium metal handled in a glovebox.
As outlined in Table 1, water content was found to have little
influence (within experimental error) on the synthesis of SmI2
under the conditions of our experiments. For example, in the
extreme case (entry 3) using very wet THF (commercially
available bottles of THF of HPLC grade typically contain
<150−250 ppm of water), SmI2 was formed with similar
efficiency. Interestingly, the induction time was found to
correlate directly with the water content, with slower reaction
time corresponding to higher water concentration.
From these experiments, we conclude that when minimal
care is taken to exclude water (the standard operating protocol
in most synthetic chemistry laboratories), water is not the
major factor hindering the synthesis of SmI2. We hypothesize
that in cases when “wet” THF was used, the longer induction
time may arise from the initial reaction of samarium metal with
water thus slowing down the reaction of the metal with 1,2-
diiodoethane. Overall, these results demonstrate that in the
synthesis of SmI2 using 1,2-diiodoethane, water is not the major
factor in failed preparations of the reagent, although long
activation times are indicative of high water content, and that
commercially available THF can be used.
Scheme 3. Synthesis of SmI2 Using 1,2-Diiodoethane
Finally, it should be noted that our studies pertain to solutions
of SmI2 rather than suspensions of SmI2. We focused our
investigation on solutions of the reagent for the following
reasons: (1) suspensions of SmI2 contain variable quantities of
samarium metal and display different properties to solutions of
SmI2 or pure SmI2 solid,27 and (2) some of the reactions
mediated by SmI2 are not compatible with the samarium metal
present in suspensions of SmI2. In all of the examples presented
in the current study (with the exception of Table 7), reactions
between samarium metal and the oxidant proceed quantita-
tively to yield suspensions of SmI2. We propose that different
physicochemical stimuli during the synthesis of SmI2 (e.g.,
changes in mechanical agitation, temperature or physical
properties of the system) might be responsible for different
properties of the resultant solutions/suspensions. At present,
we cannot exclude that complex solution equilibria are also
responsible for this difference.28 Moreover, the variable and
limited solubility of SmI2 in THF also plays a role in
determining the molarity of solutions of SmI2.29
Effect of Water. Because of its potential to react with Sm
metal, SmI3, or SmI2, the presence of water appeared to be a
likely factor impeding the synthesis of SmI2.26 To evaluate the
influence of water on the formation of SmI2, the synthesis was
performed using THF with gradually increasing water content,
as determined by a coulometric Karl Fischer titration (Table 1).
To unambiguously determine the impact of water content in
THF on the synthesis of SmI2, the THF used in entries 1−3
was prepared by sequential dilution of the same batch of
Effect of Oxygen. It is well-known that the Ln(II)
oxidation state is less stable than the Ln(III) oxidation
state.1−3,23,26 Consequently, SmI2 is unstable when exposed
to air and easily oxidizes to Sm(III) with an accompanying
color change from blue to yellow. Therefore, we next
investigated the influence of oxygen concentration on the
synthesis of SmI2 using several experimental protocols involving
gradually less rigorous conditions for the exclusion of air.
Details of these experiments are outlined in Table 2. As
expected, the use of standard Schlenk techniques and the
a
Table 2. Effect of Oxygen on the Synthesis of SmI2
c
degassing method of
induction
c
[SmI2]
(M)
b
entry
1
THF
rxn setup method
time (min)
freeze-pump thawing standard Schlenk
techniques
15
10
20
15
15
0.076
0.075
0.074
0.060
0.058
Table 1. Effect of Water Content in THF on the Synthesis of
2
3
4
5
distillation from Na/ standard Schlenk
a
Ph2CO/N2
techniques
SmI2
standard Schlenk
techniques
b
d
water content
(ppm)
induction [SmI2]
c
entry
1
THF purity
time
(M)
Ar sparging, no
d
vacuum
15
167
328
anhydrous, dried over MS
4 Å
15 min
0.076
“open flask
conditions”
e
2
3
anhydrous, dried over MS
4 Å + H2O
45 min
>2 h
0.072
0.073
a
Unless noted otherwise, all reactions were carried out using standard
anhydrous, dried over MS
4 Å + H2O
Schlenk techniques for handling air-sensitive reagents; samarium metal
(ABCR) handled in a glovebox; THF purchased from Sigma-Aldrich;
b
4
5
6
59
50
34
anhydrous
30 min
30 min
10 min
0.070
0.075
0.075
rt, 18−24 h, 5.5 mmol scale. Entry 1, three cycles of freeze−pump−
HPLC grade
thawing; entry 2, freshly distilled prior to use; entries 3−5, commercial
c
d
HPLC grade, distilled from
Ph2CO/Na
THF without any pretreatment was used. See Table 1. Reaction was
carried out without the use of high vacuum: in air, an oven-dried flask
was charged with samarium metal and 1,2-diiodoethane, sealed with
septum and placed under argon atmosphere. THF was added in one
portion, the flask was sealed with Parafilm, and the reaction mixture
a
All reactions carried out using standard Schlenk techniques for
handling air-sensitive reagents; samarium metal (ABCR) handled in a
glovebox; THF purchased from Sigma-Aldrich, rt, 18−24 h, 5.5 mmol
scale. Sm (2 equiv) and 1,2-diiodoethane (1 equiv) were used.
e
was stirred for indicated time. Reaction was carried out without the
b
c
Determined by coulometric Karl Fischer titration. Induction time
use of high-vacuum or inert gas techniques: in air, an oven-dried flask
was charged with samarium metal and 1,2-diiodoethane, fitted with
septum and THF was added in one portion. The flask was sealed with
Parafilm, and the reaction mixture was stirred for indicated time.
indicates time after which color of reaction mixture turned blue; note
d
that induction time varies with the scale of the reaction. Refers to
solutions of SmI2, performed according to ref 12 in triplicate.
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degassing of THF by means of freeze−pump−thawing or
distillation under inert atmosphere gave comparable results in
terms of reaction efficiency and induction time (entries 1 and
2).
found in Tables 1 and 2. Overall, these findings indicate that it
is unlikely that the quality of THF (including variable water,
oxygen, and peroxide content) is the major factor in failed
attempts to prepare SmI2. These results suggest that the use of
standard sources of THF available in organic chemistry
laboratories give rise to the efficient formation of the reagent.
Effect of Preparation Procedure. Three different
approaches for the combination of reagents and solvents in
the preparation of SmI2 have been reported in the literature.34
As outlined in Table 4, we found no significant difference in the
Strikingly, similar results were obtained when commercially
available solvents without any special pretreatment were used
(entry 3). Furthermore, simple argon sparging or even ‘open
flask’ conditions allowed the efficient synthesis of SmI2 (entries
4−5). These unexpected results require us to change our view on
the importance of excluding oxygen during the formation of SmI2.
(NB after formation of SmI2, the reagent should be handled
under inert gas atmosphere to prevent oxidation to Sm(III)
species).31 In cases where oxygen was deliberately allowed into
reaction vessels, excess samarium metal may react with oxygen
prior to the formation of SmI2, thus permitting efficient
synthesis of the reagent. Interestingly, when using 1,2-
diiodoethane as oxidant, the induction time does not seem to
depend on the amount of oxygen present in the reaction vessel
(however, compare to the use of Imamoto’s method, Table 5).
Importantly, these findings show that the use of strict Schlenk
techniques is not necessary for the synthesis of SmI2 and that
commercially available THF can be used for the synthesis of
SmI2 without prior degassing.
Effect of Peroxides. Peroxide-contamination is a common
problem with ethereal solvents such as THF.32 The presence of
peroxides in THF has been suggested to have a detrimental
impact on the synthesis of SmI2.19 However, by testing different
sources of THF with varying degrees of peroxide content (the
peroxide content was determined by standard reaction with
potassium iodide followed by iodometric titration with sodium
thiosulfate), we determined that it is unlikely that peroxides
interfere with the formation of SmI2 to a significant degree
(Table 3). From this study it is useful to know that both types
Table 4. Effect of Preparation Procedure on the Synthesis of
a
SmI2
c
c
induction time
(min)
[SmI2]
(M)
b
entry
1
addition procedure
addition of THF to Sm metal and
ICH2CH2I
15
20
20
0.071
0.072
0.069
2
3
addition of ICH2CH2I in THF to Sm
metal
addition of solid ICH2CH2I to Sm
metal in THF
a
All reactions carried out using standard Schlenk techniques for
handling air-sensitive reagents; samarium metal (ABCR) handled in a
glovebox, commercial THF was used w/o special pretreatment, water
b
content 100 ppm; rt, 18−24 h, 5.5 mmol scale. Entry 1: THF was
added to a flask charged with Sm metal and 1,2-diiodoethane. Entry 2:
a solution of 1,2-diiodoethane in THF was added to a flask charged
with Sm metal. Entry 3: solid 1,2-diiodoethane was added to a flask
c
charged with Sm metal and THF. See Table 1.
efficiency of formation of SmI2 using the three variants. From a
practical perspective, the procedure described in entry 1,
namely adding THF to the reaction vessel charged with
samarium metal and 1,2-diiodoethane, is the most convenient
and time-efficient (see the Experimental Section).
Factors Affecting the Synthesis of SmI2 Using
Imamoto’s Method with Iodine as the Oxidant.
Imamoto’s method is an important procedure for the
preparation of SmI2.7 Having examined potential factors
affecting the synthesis of SmI2 using 1,2-diiodoethane, we
turned our attention to the use of iodine as the oxidant (Table
5). In general, the effect of the factors examined mirrors our
findings for the formation of SmI2 using 1,2-diiodoethane.
Overall, these results demonstrate that rigorous drying of
solvents is not required for Imamoto’s method, commercial
solvents can be used as received, and simple argon sparging and
“open flask” conditions are adequate.31
Effect of Samarium Metal Quality on the Preparation
of SmI2. In the early 1990s, Brown and co-workers described
the mechanical activation of magnesium for the synthesis of
Grignard reagents, whereby solid magnesium turnings were
stirred under inert atmosphere to provide highly reactive
magnesium powder.35 This convenient procedure for the
removal of oxide from the magnesium surface provided a
platform for advances in organometallic chemistry based on the
activation of metals under simple laboratory conditions.36 To
our knowledge the dry-stirring method described by Brown has
not been used for the activation of samarium metal.
In the course of studying reactions mediated by SmI2, we and
others have noticed the negative impact of the quality of some
batches of samarium metal on the efficiency of SmI2
formation.37 In the worst cases, it has been noted that the
preparation of SmI2 using a batch of samarium metal might fail
completely under standard conditions. Since lanthanide metals
Table 3. Effect of Peroxide Content in THF on the Synthesis
a
of SmI2
d
peroxide
b
induction time [SmI2]
c
d
entry
1
content (M)
THF
(min)
(M)
0.0015
Aldrich, anhyd, 1 L,
w/o BHT
30
0.070
2
3
4
5
0.002
Aldrich, anhyd, 2 L,
w/o BHT
15
30
20
15
0.076
0.069
0.074
0.071
0.002
Acros, anhyd, 1 L,
w/o BHT
<0.001
<0.001
Aldrich, HPLC,
w/BHT
Fisher Sci., anhyd,
w/BHT
a
All reactions carried out using standard Schlenk techniques for
handling air-sensitive reagents; samarium metal (ABCR) handled in a
glovebox, rt, 18−24 h, 5.5 mmol scale. BHT = 3,5-di-tert-butyl-4-
b
hydroxytoluene. Determined by reaction with sodium thiosulfate,
c
followed by iodometric titration. See the Supporting Information for
d
details regarding batch number of THF used. See Table 1.
of THF, stabilized and unstabilized, can be used for the
synthesis of SmI2.33 Caution: when using unstabilized THF,
standard precautions regarding the handling of peroxides
should be taken.
Effect of THF Quality. THF is the mainstay solvent for the
synthesis and use of SmI2.1−5 The influence of different sources
of THF on the formation of SmI2 was tested alongside studies
on the effect of peroxide content (Table 3). Additional
experiments showing the influence of the source of THF can be
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Table 5. Effect of Selected Parameters on the Synthesis of
SmI2 Using I2
Table 6. Effect of Handling and Storage of Samarium Metal
on the Synthesis of SmI2
a
a
c
water
samarium
b
induction time
(min)
b
c
d
c
content
reaction setup
method
peroxides
(M)
induction [SmI2]
entry
1
metal
notes
[SmI2] (M)
d
entry
1
(ppm)
time
(M)
ABCR,
glovebox
5
0.072
100
Schlenk
techniques
<0.001
0.002
0.002
1 h
0.060
2
Acros,
5
0.065−0.073
2
3
110
110
Schlenk
techniques
1.5 h
0.062
0.066
glovebox
d
3
4
Acros, air
15
15
0.069
0.062
Schlenk
30 min
ABCR,
glovebox
kept in air for 10
e
techniques/
days
e
60 °C
5
Acros,
glovebox
activated by flame-
5
0.068
f
f
4
5
6
100
100
380
Ar sparging
<0.001
<0.001
<0.001
2 h
0.061
0.061
0.055
drying
f
“open flask”
>5 h
2 h
a
Unless noted otherwise, all reactions carried out using standard
Schlenk techniques for handling air-sensitive reagents; rt, 18−24 h, 5.5
or 16.5 mmol scale. See the Supporting Information for the batch
number of samarium metal used. See Table 1. Stored in a closed
container in air and frequently opened in air for use without any
precautions to exclude oxygen. Samarium metal removed from
glovebox, stored in air in an open vessel, and mixed at least two times
per day to ensure homogeneous exposure of metal surface to oxygen.
Vigorous flame-drying of samarium metal under high-vacuum.
Schlenk
techniques
b
a
c
d
Unless noted otherwise, all reactions carried out using standard
Schlenk techniques for handling air-sensitive reagents; samarium metal
(ABCR) handled in a glovebox; commercial THF without special
pretreatment was used; rt, 18−24 h, 5.5 mmol scale. Determined by
coulometric Karl Fischer titration. Determined by reaction with
sodium thiosulfate, followed by iodometric titration. See Table 1.
Reaction performed at 60 °C. See Table 2.
e
b
c
d
f
e
f
(b) stored in a closed container in air and frequently opened for
use in air without taking any precautions (entry 3), or (c)
stored in a completely open container in air (entry 4). Our
study therefore suggests that samarium metal is much more
stable in air than has been indicated in the literature.
Overall, our findings demonstrate that as long as the
samarium metal is “active”, which in our experience is the
case with the majority of commercial batches, simple
techniques and equipment are sufficient to handle samarium
metal for the formation of SmI2. Notably, the metal can be
stored on the bench in air and special precautions are not
necessary during the weighing of samples.
Activation of “Inactive” Samarium Metal. Next, we
addressed the problem of activating “inactive” samarium metal.
Our objective was to develop a convenient, “foolproof” method
for the preparation of SmI2 from any batch of samarium
metal.38,39 For this study we selected different batches of
samarium metal that failed to form SmI2 under standard and
more forcing conditions (Table 7, entries 1 and 2). We
reasoned that the dry-stirring method described by Brown
could provide a convenient method for the activation of
“inactive” samarium metal for use in the synthesis of SmI2.
After some experimentation, we were delighted to find that
activation of an “inactive” batch of samarium metal by dry-
stirring under argon, followed by oxidation with iodine, gave
SmI2 in excellent yield (Table 7, entries 3 and 4). Furthermore,
we demonstrated that SmI2 prepared from “inactive” samarium
metal is an efficient electron transfer reductant in a variety of
challenging SmI2-mediated transformations (Table 8).25 In all
cases, yields were comparable to or higher than those
previously reported, testifying to the utility of the SmI2
solutions prepared using our activation protocol.
Next, we applied this activation method to other “inactive”
batches of samarium metal (Table 7). Interestingly, we found
that the dry-stirring activation method does not work when 1,2-
diiodoethane is used as oxidant (entries 5 and 6). We
hypothesize that additional activation of samarium metal
surface by iodine under thermal conditions might explain the
efficiency of the processes described in entries 3 and 4 of Table
7. However, for some “inactive” batches of samarium metal, the
use of 1,2-diiodoethane at higher concentrations activates the
are oxygen sensitive, we hypothesized that the major factor
preventing efficient formation of SmI2 using “inactive” batches
of samarium metal is an oxide coating on the metal surface.
Interestingly, we found no pattern in encountering “inactive”
batches of samarium metal from commercial suppliers. For
example, following a long period of good quality samarium
metal from a supplier, an “inactive” batch would be
encountered, followed again by bottles of good quality metal.
As we have encountered this problem with different suppliers at
different times, it appears to indicate potential issues with the
storage of samarium metal prior to distribution or an occasional
issue with the quality of the world supply of samarium metal.
In light of our findings (Tables 1−5), we propose that most
of the difficulties reported in the preparation of SmI2 over the
last 30 years originate from “inactive” batches of samarium
metal from commercial suppliers. In some cases, such an
experience prevents users from pursuing the use of the reagent.
Moreover, it is likely that literature reports of low yields from
SmI2-mediated reactions may often arise from the use of low
quality samarium metal in the preparation of the reagent. It is
important to note that SmI2 solutions prepared from low
quality samarium metal are likely to contain an unusually high
content of SmI3 and exhibit low stability. Clearly, the inability
to reliably prepare SmI2 from all batches of commercial
samarium metal has prevented an even wider use of SmI2 in
synthesis and slowed the full realization of the reagent’s
potential.
To investigate the problem of variable samarium metal
quality, we first studied the impact of different conditions for
the storing and handling of samarium metal (Table 6). For this
study we selected batches of samarium metal that had already
been shown to be effective for the formation of the reagent. As
outlined above, literature procedures for the synthesis of SmI2
often emphasize the importance of handling samarium metal
under inert atmosphere conditions and involve metal flame-
drying techniques aimed at activating the metal surface.15,17,18
However, in our studies (Table 6) we found no significant
difference in the efficiency of SmI2 formation using the same
batches of samarium metal that were (a) handled under strictly
inert atmosphere conditions in a glovebox (entries 1 and 2),
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a
Table 7. Synthesis of SmI2 from “Inactive” Samarium Metal
b
c
d
d
entry
samarium metal
activation of samarium metal
synthesis method
notes
rt, 6 d
induction time
[SmI2] (M)
e
1
2
Strem
n/a
n/a
ICH2CH2I
not formed
e
Strem
I2
60 °C, 3 d
60 °C, 18 h
60 °C, 18 h
rt, 18 h
not formed
f
3
Strem
dry-stirring under Ar, 24 h
I2
2 h
5 h
0.084
0.081
g
4
Strem
dry-stirring under vacuum, 150 °C, 20 h
I2
f
e
5
Strem
dry-stirring under Ar, 24 h
ICH2CH2I
ICH2CH2I
ICH2CH2I
ICH2CH2I
I2
not formed
h
e
6
Strem
thermal activation
rt, 18 h
not formed
i
7
Strem
10−55 mL
10−55 mL
10−55 mL
rt, 2 d, 1 d
rt, 1 d, 1 d
rt, 1 d, 1 d
rt, 1 d
>5 h
>5 h
>5 h
0.057
0.072
0.047
i
8
Strem
i
9
Strem
e
10
11
12
13
AlfaAesar
AlfaAesar
ABCR
ABCR
n/a
ICH2CH2I
I2
not formed
f
dry-stirring under Ar, 24 h
60 °C, 18 h
rt, 1 d
15 min
0.083
e
n/a
ICH2CH2I
I2
not formed
f
dry-stirring under Ar, 24 h
60 °C, 18 h
15 min
0.099
a
b
All reactions carried out using standard Schlenk techniques for handling air-sensitive reagents; all reactions performed on 5.5 mmol scale. See the
c
d
Supporting Information for batch number of samarium metal used. Refers to conditions used for the synthesis of SmI2. See Table 1; the
e
concentration for entries 11 and 13 was determined for suspensions of SmI2. Indicates that the blue color characteristic of SmI2 did not form.
f
g
Samarium metal was stirred under argon at rt for indicated time, followed by addition of THF and oxidant. Samarium metal was stirred under high-
h
i
vacuum at 150 °C for indicated time, followed by addition of THF and oxidant. Activation of metal by vigorous flame-drying under vacuum. 1,2-
Diiodoethane and samarium metal stirred in 10 mL of THF for indicated time, followed by addition of the remaining portion of THF.
Table 8. Electron-Transfer Reductions Mediated by SmI2 Prepared from “Inactive” Samarium Metal
a
1
Determined by H NMR.
samarium metal surface (entries 7−9). However, this protocol
has not been found to be as general as the dry-stir method
followed by reaction with iodine (entries 3 and 4).
Having worked with samarium metal of differing quality, we
have noticed that “active” and “inactive” batches of samarium
metal often differ in physical appearance. Consequently, we
have developed a simple test to determine whether a particular
batch of samarium metal is likely to be “active” or “inactive” for
the synthesis of SmI2.40
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In summary, our studies have shown that the synthesis of
SmI2 using “active” samarium metal is remarkably robust and
that “inactive” samarium metal can be activated by dry-stirring.
Thus, we have developed a “foolproof” protocol for the
synthesis of SmI2 from any batch of commercial samarium
metal.
Scheme 4. Evaluating the Use of Commercial SmI2 Solutions
for the Reduction of Aliphatic Esters
Stability of Solutions of SmI2 in THF. The stability of
solutions of SmI2 in THF is a key issue in the study of reactions
mediated by the reagent. In general, it has been recommended
that SmI2 should be freshly prepared before each use as
problems with the stability of the reagent have been frequently
reported.2−5,20
low concentration of the commercial solutions, the yields
obtained were comparable to those obtained with SmI2
prepared fresh using Kagan’s or Imamoto’s method. Thus,
commercial THF solutions are effective sources of SmI2 for
preliminary studies.
We have therefore examined the stability of SmI2 prepared
by Kagan’s method, and in contrast to some literature reports,
we have found that solutions of the reagent are reasonably
stable. No sign of decomposition was detected after a period of
one month when the reagent was simply sealed under inert
atmosphere and stored on the bench at room temperature with
stirring. On the other hand, we have noticed a propensity for
SmI2 to precipitate with time from unstirred THF solutions.
The limited solubility of SmI2 in THF may affect dynamic
equilibria between SmI2, Sm metal, SmI3 and other complexes
of Sm(II) and likely plays an important role in the stability of
the reagent.27−29 Furthermore, we have found that SmI2 can be
conveniently stored at room temperature under inert
atmosphere without stirring for long periods of time (>2
weeks). However, the reagent should be stirred for at least 1 h
prior to use. Studies to elucidate these intriguing features of
SmI2 solutions are currently ongoing in our group.
In contrast to SmI2 prepared from 1,2-diiodoethane, we
determined that THF solutions of SmI2 prepared from iodine
are significantly less stable; visible decomposition was observed
after several days. We ascribe this difference to more efficient
activation of samarium metal by 1,2-diiodoethane than by
iodine. Accordingly, we recommend that in cases when SmI2
solutions prepared using Imamoto’s method give variable
results, reactions should be repeated using SmI2 prepared from
1,2-diiodoethane. From an experimental perspective, it is very
useful to know that THF solutions of SmI2 can be stored
provided they are stirred prior to use.
CONCLUSIONS
■
Our studies show that the use of samarium metal and 1,2-
diiodoethane or iodine for the formation of SmI2 reliably
provides the reagent under experimental conditions that are
more convenient than those typically employed in literature.
We have found that the formation of SmI2 is remarkably
resilient to the presence of water, oxygen and peroxides and
thus we have dispelled many of the myths surrounding the
reagent. In fact, SmI2 is ideally suited for widespread use in all
synthetic chemistry laboratories, including those that do not
have access to specialized glovebox or high-vacuum equipment,
high quality solvents and reagents. We have shown that when
SmI2 fails to form efficiently it is likely to be a result of low
quality samarium metal. Accordingly, we have developed a
“foolproof” protocol for the activation of “inactive” batches of
samarium metal and have demonstrated the utility of SmI2
generated in this way. Our studies also suggest that SmI2
solutions can be stored, however, complex equilibria might play
a role in altering the properties of the solutions if they are not
stirred. Finally, we have showed that commercially available
solutions of SmI2 in THF are effective, although much lower
than advertized molarities should be expected. We expect our
findings to be of broad utility for all practitioners of organic
chemistry who require a user-friendly electron transfer
reductant, such as SmI2.
Working with Commercial Solutions of SmI2. SmI2 is
available from several commercial suppliers as a “0.l M solution
in THF”. Examination of the literature suggests that
commercial solutions of SmI2 vary significantly in concentration
from the advertized value.12 Furthermore, the use of
commercial solutions of SmI2 have been reported to give
variable results and low yields in SmI2-mediated reactions,
suggesting that there are problems with the stability of
commercial solutions of the reagent.22
To gain independent insight into this issue, we evaluated
several different batches of SmI2 from commercial sources (see
the Supporting Information, Table SI-1, for full details). We
found that the average concentration of commercial SmI2 (0.04
M from four different suppliers) was much lower than the
advertised 0.1 M concentration. This finding is in good
agreement with other literature reports.12
Since the commercial availability of SmI2 solutions in THF
contributes to the widespread use of the reagent, we sought to
demonstrate that commercial solutions are viable sources of
SmI2. Toward this end, we performed a series of challenging
electron transfer reductions using aliphatic ester 1 as a model
substrate25e (Scheme 4, see the Supporting Information for
additional examples). In all cases, after taking into account the
EXPERIMENTAL SECTION
■
General Methods. All experiments were performed under an
atmosphere of argon or nitrogen, using anhydrous solvents, unless
stated otherwise. THF was purchased and purified by passing through
activated alumina columns, distillation from sodium/benzophenone,
or used as received. Samarium metal was purchased and used as
received. 1,2-Diiodoethane was stored at 4 °C and used after
purification as described below. All other solvents and chemicals
were used without further purification or drying procedures. Reaction
glassware was oven-dried overnight at 140 °C or flame-dried prior to
use and cooled under vacuum then purged with argon. H and 13C
1
NMR spectra were recorded on 300, 400, and 500 MHz
spectrometers. Unless otherwise noted, all samples were dissolved in
CDCl3, and the shifts are reported in parts per million (ppm) relative
to residual CHCl3 as an internal standard (1H NMR δ = 7.27 or 13C
NMR δ = 77.2). Abbreviations are: s, singlet; d, doublet; t, triplet; q,
quartet; br s, broad singlet. All coupling constants (J) are reported in
hertz (Hz). All flash chromatography was performed using silica gel,
60 Å, 230−400 mesh. TLC analysis was carried out on aluminum
sheets coated with silica gel 60 F254, 0.2 mm thickness. The plates
were visualized using a 254 nm ultraviolet lamp or aqueous potassium
permanganate solutions. Products were identified using 1H NMR
analysis and comparison with authentic samples.
Typical Procedure for the Preparation of SmI2. An oven-dried
100 mL round-bottomed flask equipped with a Teflon-coated
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magnetic stir bar and a septum was placed under vacuum and
evacuated/backfilled with argon three times. Note: the flask can also
be flame-dried under vacuum, followed by three evacuation/backfilling
cycles. In air, 1.65 g (11.0 mmol) of samarium metal and 1.55 g (5.5
mmol) of freshly washed 1,2-diiodoethane (see, below) was weighed
out and added to the reaction flask. The flask was sealed with a
septum, evacuated/backfilled with argon three times, and stirring was
started at medium speed. 55 mL of commercial THF (Sigma-Aldrich,
anhyd, used as received) was added using a 60 mL syringe. The flask
was evacuated/backfilled with argon three times (this process removes
ethylene formed during the insertion of Sm into 1,2-diiodoethane), the
argon line was removed, and the septum was sealed with Parafilm.
Note: the reaction can also be conveniently stirred under a positive
pressure of argon. After stirring overnight, the stirring was turned off,
and the solution of SmI2 was allowed to settle for 30 min and titrated
according to ref 12 and/or 11.
Procedure for Purifying Commercial 1,2-Diiodoethane. 1,2-
Diiodoethane (20 g) was dissolved in approximately 400 mL of diethyl
ether, and the organic layer was washed with aqueous saturated
sodium thiosulfate solution (5 × 100 mL) and water (1 × 100 mL),
dried over sodium sulfate, and concentrated to give a white solid. The
flask containing 1,2-diiodoethane was wrapped in aluminum foil and
placed under high-vacuum for 30 min.
Typical Procedure for the Preparation of SmI2 from
“Inactive” Samarium Metal. A 100 mL Schlenk tube equipped
with a Teflon-coated magnetic stir bar (24 × 12 mm) and a septum
was flame-dried under vacuum. Note: an oven-dried Schlenk tube can
also be used. The tube was allowed to cool to room temperature and
evacuated/backfilled with argon three times. 1.65 g (11.0 mmol) of
“inactive” samarium metal was added, the tube was sealed with a
septum and subjected to three evacuation/backfilling cycles. After the
final cycle, the tube was left under a positive pressure of argon, and
stirring was started at medium to high speed. After the mixture was
stirred for 24 h, 45 mL of THF was added, followed by 1.40 g (5.5
mmol) of iodine dissolved in 10 mL of THF under argon. The
reaction flask was sealed with Parafilm and heated at 60 °C for 18 h.
The stirring was turned off and the solution of SmI2 was allowed to
settle for 2 h and titrated according to ref 12 and/or 11.
samarium(II) iodide (THF solution) followed by water under
inert atmosphere at room temperature and the mixture stirred
vigorously. After the specified time, the reaction mixture was
diluted with CH2Cl2 (30 mL) and HCl (1 N, 30 mL). The
aqueous layer was extracted with CH2Cl2 (3 × 30 mL), and the
organic layers were combined, dried over Na2SO4, filtered and
1
concentrated. The sample was analyzed by H NMR to obtain
conversion and yield using internal standard.
General Procedure II (for Reactions in Table 8). To acyclic ester or
carboxylic acid was added samarium(II) iodide (THF solution)
followed by amine and water under inert atmosphere at room
temperature and the mixture stirred vigorously. After the specified
time, the excess of SmI2 was oxidized by bubbling air through the
reaction mixture. The reaction mixture was diluted with CH2Cl2 (30
mL) and HCl (1 N, 30 mL). The aqueous layer was extracted with
CH2Cl2 (3 × 30 mL), and the organic layers were combined, dried
over Na2SO4, filtered, and concentrated. The sample was analyzed by
1H NMR to obtain conversion and yield using internal standard.
2-(3-Hydroxypropyl)phenol (Table 8, Entry 1). According to the
general procedure I, the cyclic ester was reacted with samarium(II)
iodide (8 equiv) and water (200 equiv) to give the title product in 99%
1
yield: H NMR (500 MHz, CDCl3) δ 1.78−1.84 (m, 2H), 2.51 (br,
1H), 2.71 (t, J = 6.8 Hz, 2H), 3.57 (t, J = 5.8 Hz, 2H), 6.76−6.82 (m,
2H), 7.02−7.05 (m, 2H), 7.06 (br, 1H); 13C NMR (125 MHz,
CDCl3) δ 25.1, 32.2, 60.8, 116.1, 120.8, 127.2, 127.6, 130.7, 154.6.
Spectroscopic properties matched those previously described.25a
2-(2-(Hydroxymethyl)phenyl)ethanol (Table 8, Entry 2). Accord-
ing to the general procedure I, the cyclic ester was reacted with
samarium(II) iodide (8 equiv) and water (200 equiv) to give the title
1
product in 65% yield: H NMR (300 MHz, CDCl3) δ 2.75 (t, J = 6.0
Hz, 2H), 3.64 (t, J = 6.0 Hz, 2H), 4.07 (br, 2H), 4.43 (s, 2H), 7.07−
7.21 (m, 4H); 13C NMR (75 MHz, CDCl3) δ 35.1, 62.9, 63.2, 126.7,
128.5, 129.7, 130.1, 138.3, 139.2. Spectroscopic properties matched
those previously described.25a
1-Adamantanemethanol (Table 8, Entry 3). According to the
general procedure II, the ester was reacted with samarium(II) iodide
(12 equiv), triethylamine (72 equiv), and water (72 equiv) to give the
1
title product in 97% yield: H NMR (500 MHz, CDCl3) δ 1.23 (br,
1H), 1.44 (m, 6H), 1.57 (m, 1H), 1.59 (m, 2H), 1.65 (m, 2H), 1.68
(m, 1H), 1.92 (m, 3H), 3.13 (s, 2H); 13C NMR (125 MHz, CDCl3) δ
28.2, 34.5, 37.2, 39.0, 73.9. Spectroscopic properties matched those
previously described.25e
Typical Procedure for the Preparation of SmI2 with Inert Gas
Sparging. Kagan’s Method. An oven-dried 100 mL round-
bottomed flask equipped with a Teflon-coated magnetic stir bar and
a septum was placed under a positive pressure of inert gas (argon or
nitrogen). In air, 1.65 g (11.0 mmol) of samarium metal and 1.55 g
(5.5 mmol) of freshly washed 1,2-diiodoethane (see, above) were
weighed out and added to the reaction flask. The flask was sealed with
a septum, and stirring was started at medium speed. Commercial THF
(55 mL, Sigma-Aldrich, anhyd, used as received) was added using a 60
mL syringe, the argon line was removed, and the septum was sealed
with Parafilm. Note: the reaction can also be conveniently stirred
under a positive pressure of argon. After stirring overnight, stirring was
stopped and the solution of SmI2 was allowed to settle for 30 min and
titrated according to ref 12 and/or 11.
2-(1H-Indol-3-yl)ethanol (Table 8, Entry 4). According to the
general procedure II, the ester was reacted with samarium(II) iodide
(8 equiv), triethylamine (36 equiv) and water (36 equiv) to give the
1
title product in 99% yield: H NMR (500 MHz, CDCl3) δ 1.47 (br,
1H), 2.97 (t, J = 6.3 Hz, 2H), 3.84 (t, J = 6.3 Hz, 2H), 7.01 (d, J = 1.5
Hz, 1H), 7.06 (t, J = 7.0 Hz, 1H), 7.14 (t, J = 7.5 Hz, 1H), 7.30 (d, J =
8.2 Hz, 1H), 7.56 (d, J = 7.9 Hz, 1H), 7.99 (br, 1H); 13C NMR (125
MHz, CDCl3) δ 28.8, 62.6, 111.3, 112.3, 118.9, 119.5, 122.3, 122.5,
127.4, 136.5. Spectroscopic properties matched those previously
described.25e
3-Phenylpropan-1-ol (Table 8, Entry 5). According to the general
procedure II, the acid was reacted with samarium(II) iodide (6 equiv),
triethylamine (36 equiv) and water (36 equiv) to give the title product
in 84% yield. 1H NMR (500 MHz, CDCl3) δ 1.27 (br, 1H), 1.80−1.86
(m, 2H), 2.64 (t, J = 7.5 Hz, 2H), 3.61 (t, J = 6.5 Hz, 2H), 7.10−7.24
(m, 5H); 13C NMR (125 MHz, CDCl3) δ 32.1, 34.3, 62.3, 125.9,
128.4, 128.5, 141.8. Spectroscopic properties matched those previously
described.25e
Typical Procedure for the Preparation of SmI2 with Inert Gas
Sparging. Imamoto’s Method. An oven-dried 100 mL round-
bottomed flask equipped with a Teflon-coated magnetic stir bar and a
septum was placed under a positive pressure of inert gas (argon or
nitrogen). In air, 1.65 g (11.0 mmol) of samarium metal was weighed
out and added to the reaction flask. Commercial THF (55 mL, Sigma-
Aldrich, anhyd, used as received) was then added using a 60 mL
syringe. Finally, 1.40 g (5.5 mmol) of iodine was added, the flask was
sealed with a septum, and stirring was started at medium speed. The
argon line was then removed, and the septum was sealed with Parafilm.
Note: the reaction can also be conveniently stirred under a positive
pressure of argon. After stirring overnight at room temperature or 60
°C, stirring was stopped (when the reaction was performed at 60 °C, it
was allowed to cool to room temperature), the solution of SmI2 was
allowed to settle for 30 min, and titrated according to ref 12 and/or 11.
Experimental Procedures for Reactions Mediated by SmI2
Prepared from Inactive Samarium Metal. General Procedure I
(for Reactions in Table 8). To cyclic ester was added
Decan-1-ol (Table 8, Entry 6). According to the general procedure
II, the acid was reacted with samarium(II) iodide (6 equiv),
triethylamine (36 equiv) and water (36 equiv) to give the title
1
product in 89% yield: H NMR (500 MHz, CDCl3) δ 0.81 (t, J = 6.9
Hz, 3H), 1.15−1.33 (m, 15H), 1.47−1.52 (m, 2H), 3.57 (t, J = 5.8 Hz,
2H); 13C NMR (125 MHz, CDCl3) δ 14.1, 22.7, 25.7, 29.3, 29.4, 29.6,
29.6, 31.9, 32.8, 63.1. Spectroscopic properties matched those
previously described.25e
3-Hydroxy-2-(4-methoxybenzyl)propanoic Acid (Table 8, Entry
7). To a solution of samarium(II) iodide (THF solution, 8 equiv) was
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added water (1200 equiv), followed by cyclic 1,3-diester dissolved in
2.0 mL of THF under inert atmosphere at room temperature and the
mixture stirred vigorously. After the specified time, the reaction
mixture was diluted with CH2Cl2 (30 mL) and HCl (1 N, 30 mL).
The aqueous layer was extracted with CH2Cl2 (3 × 30 mL), and the
organic layers were combined, dried over Na2SO4, filtered, and
concentrated. The sample was analyzed by 1H NMR to obtain
end point is reached when the solution changes to a yellow color.
Note: all syringes and solvents used in the procedure should be flushed
with argon (three times) and degassed prior to use to obtain
reproducible results. The titration should be repeated to give the
average of three experiments.
3. Procedure for Titration of Suspensions of SmI2.12a To a stirred
suspension of SmI2 (approximately 5.5 mmol) was added 4-tert-
butylcyclohexanone (5.5 mmol), followed by triethylamine (22.0
mmol) and water (22.0 mmol). After 5 min, the reaction was
transferred to a separatory funnel, diluted with CH2Cl2 (100 mL) and
1.0 M HCl (100 mL), extracted with CH2Cl2 (5 × 100 mL), dried, and
concentrated. The molarity of the suspension of SmI2 was determined
1
conversion and yield using internal standard: yield 98%; H NMR
(500 MHz, CDCl3) δ 2.81−2.90 (m, 2H), 2.99−2.08 (m, 1H), 3.72−
3.77 (m, 1H), 3.79−3.83 (m, 1H), 3.81 (s, 3H), 6.86 (d, J = 8.8 Hz,
2H), 7.15 (d, J = 8.8 Hz, 2H); 13C NMR (125 MHz, CDCl3) δ 33.2,
49.0, 55.3, 61.9, 114.0, 130.0, 130.2, 158.3, 179.7. Spectroscopic
properties matched those previously described.25b
1
from analysis of the product distribution by H NMR (400 MHz).
Note: other ketones can also be conveniently used for this titration.
The amount of ketone used must be less than the amount required for
full reduction by the formed suspension of SmI2.
rac-(1R,2S,3S)-Ethyl 2-Hydroxy-1-(3-hydroxypropyl)-3-methylcy-
clopentanecarboxylate (Table 8, Entry 8). To a solution of cyclic
ester in THF (2.0 mL) and water (1200 equiv) was added
samarium(II) iodide (THF solution, 7 equiv) via syringe pump over
1 h under inert atmosphere at room temperature. When the addition
was complete, the reaction mixture was diluted with CH2Cl2 (30 mL)
and HCl (1 N, 30 mL). The aqueous layer was extracted with CH2Cl2
(3 × 30 mL), and the organic layers were combined, dried over
ASSOCIATED CONTENT
■
S
* Supporting Information
Discussion regarding commercial solutions of SmI2, Table SI-1,
1
detailed list of reagents used, H and 13C NMR spectra. This
1
Na2SO4, filtered, and concentrated. The sample was analyzed by H
NMR to obtain conversion and yield using internal standard: yield
88%, dr = 7:1; 1H NMR (300 MHz, CDCl3) (major diastereoisomer)
δ 0.96 (d, J = 6.6 Hz, 3H), 1.19 (t, J = 6.9 Hz, 3H), 1.25−2.02 (m,
10H), 2.14−2.26 (m, 1H), 3.49−3.65 (m, 2H), 4.07 (q, J = 6.9 Hz,
2H), 4.12 (d, J = 3.0 Hz, 1H); 13C NMR (75 MHz, CDCl3) δ 14.2,
14.2, 28.8, 29.2, 29.9, 32.5, 38.1, 59.6, 60.6, 62.8, 78.7, 176.5.
Spectroscopic properties matched those previously described.25a
Experimental Procedures for Reactions Mediated by
Commercial Solutions of SmI2. Experimental Procedure for
Reduction of Aliphatic Esters and Carboxylic Acids. To acid or
ester (neat) was added SmI2 (THF solution, typically, 6 equiv),
followed by amine (typically, 36 equiv) and water (typically, 36
equiv) under inert atmosphere at room temperature and the
mixture stirred vigorously. After the specified time (typically,
15−18 h), the excess of SmI2 was oxidized by bubbling air
through the reaction mixture. The reaction mixture was diluted
with CH2Cl2 (30 mL) and HCl (1 N, 30 mL). The aqueous
layer was extracted with CH2Cl2 (3 × 30 mL), and the organic
layers were combined, dried over Na2SO4, filtered, and
material is available free of charge via the Internet at http://
pubs.acs.org.
AUTHOR INFORMATION
■
Corresponding Author
*Tel: (+44) 161-275-1425. Fax: (+44) 161-275-4939. E-mail:
david.j.procter@manchester.ac.uk. Homepage: http://people.
man.ac.uk/∼mbdssdp2/.
ACKNOWLEDGMENTS
■
We thank the EPRSC and GSK for support.
REFERENCES
■
(1) (a) Namy, J. L.; Girard, P.; Kagan, H. B. Nouv. J. Chim. 1977, 1, 5.
(b) Girard, P.; Namy, J. L.; Kagan, H. B. J. Am. Chem. Soc. 1980, 102,
2693. (c) Namy, J. L.; Girard, P.; Kagan, H. B.; Caro, P. E. Nouv. J.
Chim. 1981, 5, 479.
1
concentrated. The sample was analyzed by H NMR to obtain
(2) Procter, D. J.; Flowers, R. A., II; Skrydstrup, T. Organic Synthesis
Using Samarium Diiodide: A Practical Guide; RSC Publishing:
Cambridge, 2009.
conversion and yield (vs internal standard). Spectroscopic
properties of all products matched those previously described.25
Additional Experiments and Procedures. Titration Proce-
dures. Titration with H2O−Et3N System.12a An oven-dried 4-
dram vial equipped with a stirring bar and septum was placed
under a high-vacuum line, subjected to three evacuation/
backfilling cycles with argon, and left under a positive pressure
of argon. A solution of SmI2 (typically, 1.0 mL, the exact
volume of added SmI2 has to be carefully noted) was added,
followed by Et3N (0.21 mL) and H2O (33 mg). The resulting
solution was titrated with cyclohexanone (THF solution) until
the color changed from dark brown to white. The end point
was recorded when the solution changed from light green to
white. Note: other ketones can also be used for the titration
procedure. Note: all syringes and solvents used in the
procedure should be flushed with argon (three times) and
degassed prior to use to obtain reproducible results. The
titration should be repeated to give the average of three
experiments.
(3) For general reviews on SmI2, see: (a) Kagan, H. B.; Namy, J. L.
Tetrahedron 1986, 42, 6573. (b) Kagan, H. B. Tetrahedron 2003, 59,
10351. (c) Gopalaiah, K.; Kagan, H. B. New J. Chem. 2008, 32, 607.
(d) Molander, G. A. Chem. Rev. 1992, 92, 29. (e) Molander, G. A. Org.
React. 1994, 46, 211. (f) Molander, G. A.; Harris, C. R. Chem. Rev.
1996, 96, 307. (g) Molander, G. A.; Harris, C. R. Tetrahedron 1998,
54, 3321. (h) Krief, A.; Laval, A. M. Chem. Rev. 1999, 99, 745. (i) Steel,
P. G. J. Chem. Soc., Perkin Trans. 1 2001, 2727. (j) Skrydstrup, T.
Angew. Chem., Int. Ed. 1997, 36, 345. (k) Concellon
Solla, H. Chem. Soc. Rev. 2004, 33, 599. (l) Concellon
Rodríguez-Solla, H.; Concellon, C.; del Amo, V. Chem. Soc. Rev. 2010,
́
, J. M.; Rodríguez-
́
, J. M.;
́
39, 4103. (m) Beemelmanns, C.; Reissig, H. U. Chem. Soc. Rev. 2011,
40, 2199. (n) Flowers, R. A., II. Synlett 2008, 1427. (o) Harb, Y. H.;
Procter, D. J. Synlett 2012, 23, 6.
(4) For reviews on the use of SmI2 in natural product synthesis, see:
(a) Edmonds, D. J.; Johnston, D.; Procter, D. J. Chem. Rev. 2004, 104,
3371. (b) Nicolaou, K. C.; Ellery, S. P.; Chen, J. S. Angew. Chem., Int.
Ed. 2009, 48, 7140. (c) Szostak, M.; Procter, D. J. Angew. Chem., Int.
Ed. 2011, 50, 7737.
(5) For reviews on the influence of additives on properties of SmI2,
see: (a) Kagan, H. B.; Namy, J. L. Lanthanides: Chemistry and Use in
Organic Synthesis; Kobayashi, S., Ed.; Springer: New York, 1999; p 155.
2. Iodometric Titration.11 An oven-dried 4-dram vial equipped with
a stirring bar and septum was charged with iodine (26.5 mg), placed
under a high-vacuum line, and subjected to three evacuation/
backfilling cycles with argon, and THF was added (1.0 mL). Another
vial, equipped with a stirring bar and septum, was placed under a high-
vacuum line, subjected to three evacuation/backfilling cycles with
argon, and charged with a solution of SmI2 (typically, 1.0 mL, the exact
volume of added SmI2 has to be carefully noted). A solution of SmI2
was titrated with iodine solution, prepared as described above. The
́
(b) Dahlen, A.; Hilmersson, G. Eur. J. Inorg. Chem. 2004, 3393.
(c) Szostak, M.; Spain, M.; Parmar, D.; Procter, D. J. Chem. Commun.
2012, 48, 330.
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Featured Article
(6) For recent examples, see: (a) McDonald, C. E.; Ramsey, J. D.;
Sampsell, D. G.; Butler, J. A.; Cecchini, M. R. Org. Lett. 2010, 12, 5178.
(b) Chopade, P. R.; Prasad, E.; Flowers, R. A., II. J. Am. Chem. Soc.
2004, 126, 44. (c) Prasad, E.; Flowers, R. A., II. J. Am. Chem. Soc.
2005, 127, 18093. (d) Teprovich, J. A. Jr.; Balili, M. N.; Pintauer, T.;
Flowers, R. A., II. Angew. Chem., Int. Ed. 2007, 46, 8160.
(e) Sadasivam, D. V.; Antharjanam, P. K. S.; Prasad, E.; Flowers, R.
A., II. J. Am. Chem. Soc. 2008, 130, 7228. (f) Choquette, K. A.;
Sadasivam, D. V.; Flowers, R. A., II. J. Am. Chem. Soc. 2010, 132,
17396. (g) Sadasivam, D. V.; Teprovich, J. A., Jr.; Procter, D. J.;
Flowers, R. A., II. Org. Lett. 2010, 12, 4140. (h) Amiel-Levy, M.; Hoz,
S. J. Am. Chem. Soc. 2009, 131, 8280. (i) Choquette, K. A.; Sadasivam,
D. V.; Flowers, R. A., II. J. Am. Chem. Soc. 2011, 133, 10655.
(7) Imamoto, T.; Ono, M. Chem. Lett. 1987, 501.
(19) (a) Fournier, D.; Poirier, D. Eur. J. Med. Chem. 2011, 46, 4227.
(b) Brandukova, N. E.; Vygodskii, Y. S.; Vinogradova, S. V. Russ. Chem.
Rev. 1994, 63, 345.
(20) (a) Patin, A.; Kanazawa, A.; Philouze, C.; Greene, A. E.; Muri,
E.; Barreiro, E.; Costa, P. C. C. J. Org. Chem. 2003, 68, 3831.
(b) Anderson, J. C.; Chapman, H. A. Synthesis 2006, 3309. (c) Marko,
I. E.; Vanherck, J. C.; Ates, A.; Tinant, B.; Declerq, J. P. Tetrahedron
Lett. 2003, 44, 3333. (d) Linderman, R. J.; Cusack, K. P.; Kwochka, W.
R. Tetrahedron Lett. 1994, 35, 1477. (e) Frasca, J. D. Honors Thesis,
Baylor University, 2007. (f) Taylor, R. E.; Galvin, G. M.; Hilfiker, K.
A.; Chen, Y. J. Org. Chem. 1998, 63, 9580. (g) Ferreiro-Mederos, L.;
Vila-Gisbert, S.; Urbano, A.; Carreno, M. C.; Colobert, F. Org. Biomol.
̃
Chem. 2011, 9, 758. (h) Bezzenine-Lafollee
́
, S.; Guibe,
́
F.; Villar, H.;
Zriba, R. Tetrahedron 2004, 60, 6931. (i) McAuley, B. J.;
Nieuwenhuyzen, M.; Sheldrake, G. N. Org. Lett. 2000, 2, 1457.
(21) Acetonitrile: (a) Ruder, S. M. Tetrahedron Lett. 1992, 33, 2621.
(b) Maisano, T.; Tempest, K. E.; Sadasivam, D. V.; Flowers, R. A., II.
Org. Biomol. Chem. 2011, 9, 1714. Pivalonitrile: (c) Hamann, B.;
Namy, J. L.; Kagan, H. B. Tetrahedron 1996, 52, 14225. Benzene:
(d) Kunishima, M.; Hioki, K.; Kono, K.; Kato, A.; Tani, S. J. Org.
Chem. 1997, 62, 7542. Tetrahydropyran: (e) Namy, J. L.; Colomb,
M.; Kagan, H. B. Tetrahedron Lett. 1994, 35, 1723. (f) Murakami, M.;
Hayashi, M.; Ito, Y. Appl. Organomet. Chem. 1995, 9, 385. Tetraglyme:
(g) Imamoto, T.; Takeyama, T.; Yokoyama, M. Tetrahedron Lett.
1984, 25, 3225. For DME, 2-propanol, 2-methyl-2-propanol, and 2-
heptanol, see ref 11.
(8) For selected examples, see: (a) Molander, G. A.; Kenny, C. J. Org.
Chem. 1991, 56, 1439. (b) Molander, G. A.; McKie, J. A. J. Org. Chem.
1994, 59, 3186. (c) Molander, G. A.; Harris, C. R. J. Am. Chem. Soc.
́
1995, 117, 3705. (d) Monovich, L. G.; Huerou, Y. L.; Ronn, M.;
̈
Molander, G. A. J. Am. Chem. Soc. 2000, 122, 52. (e) Molander, G. A.;
Brown, G. A.; de Gracia, I. S. J. Org. Chem. 2002, 67, 3459.
(9) (a) Akane, N.; Kanagawa, Y.; Nishiyama, Y.; Ishii, Y. Chem. Lett.
1992, 2431. (b) Akane, N.; Hatano, T.; Kusui, H.; Nishiyama, Y.; Ishii,
Y. J. Org. Chem. 1994, 59, 7902.
(10) Concellon
Eur. J. Org. Chem. 2003, 1775.
́
, J. M.; Rodríguez-Solla, H.; Bardales, E.; Huerta, M.
(11) Teprovich, J. A.,
Jr.; Antharjanam, P. K. S.; Prasad, E.;
Pesciotta, E. N.; Flowers, R. A., II. Eur. J. Inorg. Chem. 2008, 5015.
(22) (a) Georg, G. I.; Cheruvallath, Z. S. J. Org. Chem. 1994, 59,
4015. (b) Caracoti, A.; Flowers, R. A., II. Tetrahedron Lett.2000, 41,
3039. (c) Sheldrake, G. N.; Soissons, N. J. Org. Chem. 2006, 71, 789.
(d) Annunziata, R.; Benaglia, M.; Cinquini, M.; Cozzi, F.; Raimondi, L.
Tetrahedron Lett. 1998, 39, 3333. (e) Orsini, F.; Sello, G.; Manzo, A.
M.; Lucci, E. M. Tetrahedron: Asymmetry 2005, 16, 1913. (f) Aaseng, J.
E. Ph.D. Thesis, Norwegian University of Science and Technology,
Trondheim, 2010.
(12) (a) Dahlen
(b) See also: Dahlen
G. Chem.Eur. J. 2005, 11, 3279.
́
, A.; Hilmersson, G. Eur. J. Inorg. Chem. 2004, 3020.
, A.; Prasad, E.; Flowers, R. A., II.; Hilmersson,
́
(13) For example, SmI2 prepared from diiodomethane could be
contaminated with trivalent samarium impurities: (a) Wayda, A. L.;
Cheng, S.; Mukerji, I. J. Organomet. Chem. 1987, 330, C17. (b) See
also: Low, C. R. M. Ultrason. Sonochem. 1995, 2, S153.
(14) For selected examples, see: (a) Williams, D. B. G.; Blann, K.;
(23) Flowers, R. A., II; Prasad, E. In Handbook on the Physics and
Holzapfel, C. W. J. Org. Chem. 2000, 65, 2834. (b) Gossinger, E.;
̈
Chemistry of Rare Earths; Gschneidner, K. A., Jr., Bunzli, J. C.,
̈
Schwartz, A.; Sereinig, N. Tetrahedron 2000, 56, 2007. (c) Foster, S. L.;
Handa, S.; Krafft, M.; Rowling, D. Chem. Commun. 2007, 4791.
(d) Enholm, E. J.; Jiang, S.; Abboud, K. J. Org. Chem. 1993, 58, 4061.
(15) For selected examples of using glovebox equipment to store Sm
metal/prepare SmI2, see: (a) Molander, G. A.; McWilliams, J. C.; Noll,
B. C. J. Am. Chem. Soc. 1997, 119, 1265. (b) Gormisky, P. E.; White,
M. C. J. Am. Chem. Soc. 2011, 133, 12584. (c) Wettergren, J.; Ankner,
T.; Hilmersson, G. Chem. Commun. 2010, 46, 7596. (d) Han, G.;
LaPorte, M. G.; Folmer, J. J.; Werner, K. M.; Weinreb, S. M. J. Org.
Chem. 2000, 65, 6293. (e) Brown, M. K.; Hoveyda, A. H. J. Am. Chem.
Soc. 2008, 130, 12904. (f) Altman, R. A.; Nilsson, B. L.; Overman, L.
E.; Read de Alaniz, J.; Rohde, J. M.; Taupin, V. J. Org. Chem. 2010, 75,
7519.
(16) For selected examples of the purification of THF for the
synthesis of SmI2, see: (a) Phillips, E. M.; Roberts, J. M.; Scheidt, K. A.
́
Org. Lett. 2010, 12, 2830. (b) Molander, G. A.; Czako, B.; Rheam, M.
J. Org. Chem. 2007, 72, 1755. (c) Ohno, H.; Wakayama, R.; Maeda, S.;
Iwasaki, H.; Okumura, M.; Iwata, C.; Mikamiyama, H.; Tanaka, T. J.
Org. Chem. 2003, 68, 5909. (d) Zheng, X.; Feng, C. G.; Ye, J. L.;
Huang, P. Q. Org. Lett. 2005, 7, 553. (e) Cha, J. Y.; Yeoman, J. T. S.;
Reisman, S. E. J. Am. Chem. Soc. 2011, 133, 14964.
Pecharsky, V. K., Eds.; Elsevier: New York, 2006; Vol. 36, p 393.
(24) For selected examples, see: (a) Johnston, D.; Francon, N.;
Edmonds, D. J.; Procter, D. J. Org. Lett. 2001, 3, 2001. (b) Hutton, T.
K.; Muir, K. W.; Procter, D. J. Org. Lett. 2003, 5, 4811. (c) McAllister,
L. A.; McCormick, R. A.; Brand, S.; Procter, D. J. Angew. Chem., Int.
Ed. 2005, 44, 452. (d) Baker, T. M.; Edmonds, D. J.; Hamilton, D.;
O’Brien, C. J.; Procter, D. J. Angew. Chem., Int. Ed. 2008, 47, 5631.
(e) Duffy, L. A.; Matsubara, H.; Procter, D. J. J. Am. Chem. Soc. 2008,
130, 1136. (f) Helm, M. D.; Da Silva, M.; Sucunza, D.; Findley, T. J.
K.; Procter, D. J. Angew. Chem., Int. Ed. 2009, 48, 9315. (g) McAllister,
L. A.; Turner, K. L.; Brand, S.; Stefaniak, M.; Procter, D. J. J. Org.
Chem. 2006, 71, 6497.
(25) For selected examples, see: (a) Parmar, D.; Duffy, L. A.;
Sadasivam, D. V.; Matsubara, H.; Bradley, P. A.; Flowers, R. A., II.;
Procter, D. J. J. Am. Chem. Soc. 2009, 131, 15467. (b) Guazzelli, G.; De
Grazia, S.; Collins, K. D.; Matsubara, H.; Spain, M.; Procter, D. J. J.
Am. Chem. Soc. 2009, 131, 7214. (c) Collins, K. D.; Oliveira, J. M.;
Guazzelli, G.; Sautier, B.; De Grazia, S.; Matsubara, H.; Helliwell, M.;
Procter, D. J. Chem.Eur. J. 2010, 16, 10240. (d) Parmar, D.; Price,
K.; Spain, M.; Matsubara, H.; Bradley, P. A.; Procter, D. J. J. Am. Chem.
Soc. 2011, 133, 2418. (e) Szostak, M.; Spain, M.; Procter, D. J. Chem.
Commun. 2011, 47, 10254. (f) Szostak, M.; Spain, M.; Procter, D. J.
Org. Lett. 2012, 14, 840. (g) Sautier, B.; Lyons, S. E.; Webb, M. R.;
Procter, D. J. Org. Lett. 2012, 14, 146. (h) Baker, T. M.; Sloan, L. A.;
Choudhury, L. H.; Murai, M.; Procter, D. J. Tetrahedron: Asymmetry
2010, 21, 1246.
(17) Shriver, D. F.; Drezdzon, M. A. The Manipulation of Air-Sensitive
Compounds; John Wiley & Sons: New York, 1986.
(18) For selected examples of flame-drying Sm metal, see: (a) Lange,
G. L.; Gottardo, C.; Merica, A. J. Org. Chem. 1999, 64, 6738.
(b) Reddy, P. P.; Yen, K. F.; Uang, B. J. J. Org. Chem. 2002, 67, 1034.
(c) Lowe, J. T.; Panek, J. S. Org. Lett. 2008, 10, 3813. (d) Reisman, S.
E.; Ready, J. M.; Hasuoka, A.; Smith, C. J.; Wood, J. L. J. Am. Chem.
Soc. 2006, 128, 1448. (e) Kakiuchi, K.; Minato, K.; Tsutsumi, K.;
Morimoto, T.; Kurosawa, H. Tetrahedron Lett. 2003, 44, 1963. (f) Liu,
X. K.; Qiu, S.; Xiang, Y. G.; Ruan, Y. P.; Zheng, X.; Huang, P. Q. J. Org.
Chem. 2011, 76, 4952. (g) Kraus, G. A.; Sy, J. O. J. Org. Chem. 1989,
54, 77.
(26) Kagan, H. B.; Namy, J. L. In Handbook on the Physics and
Chemistry of Rare Earths; Gschneidner, K. A., Jr., Eyring, L., Eds.;
Elsevier: New York, 1984; Vol. 6, p 525.
(27) It is well-known that the reactivity of SmI2/Sm suspensions
differs from that of SmI2 solutions: (a) Ogawa, A.; Takami, N.;
Sekiguchi, M.; Ryu, I.; Kambe, N.; Sonoda, N. J. Am. Chem. Soc. 1992,
114, 8729. (b) Tomisaka, Y.; Nomoto, A.; Ogawa, A. Tetrahedron Lett.
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2009, 50, 584. (c) Winkler, J. D.; Mikochik, P. J. Org. Lett. 2004, 6,
3735. (d) Fadel, A. Tetrahedron: Asymmetry 1994, 5, 531. (e) Inui, M.;
Nakazaki, A.; Kobayashi, S. Org. Lett. 2007, 9, 469.
(28) Although the reagent prepared using Kagan’s or Imamoto’s
method is described as SmI2, the correct formula for this reagent is
SmI2(THF)5 in THF solution and SmI2(THF)2 in the solid state. In
the presence of commonly used additives, for example, HMPA or
alcohols, the coordination geometry of SmI2(THF)5 undergoes further
change as new ligands are accommodated around the samarium(II)
metal center. For a relevant discussion, see: Evans, W. J.;
Gummersheimer, T. S.; Ziller, J. W. J. Am. Chem. Soc. 1995, 117,
8999. See also refs 5b and 23.
(29) For an excellent perspective on advances in lanthanide
chemistry, including the limited solubility issue, see: Evans, W. J.
Inorg. Chem. 2007, 46, 3435. See also ref 26.
(30) For practical procedures for the drying of organic solvents, see:
Williams, D. B. G.; Lawton, M. J. Org. Chem. 2010, 75, 8351.
(31) We do not imply that, when formed, SmI2 is not oxygen-
sensitive. However, SmI2 can be handled via a single gas line (argon or
nitrogen) connected to a bubbler filled with oil. For an example of
such a simple and practical setup, see: Simoneau, C. A.; Ganem, B.
Nat. Protoc. 2008, 3, 1249.
(32) Kelly, R. J. Chem. Health Safety 1996, 3, 28.
(33) Under certain conditions, SmI2 is known to react with phenols:
Kamochi, Y.; Kudo, T. Tetrahedron Lett. 1994, 35, 4169.
(34) For example, see: (Sm and 1,2-diiodoethane, then THF added)
(a) Treu, J.; Hoffmann, H. M. R. J. Org. Chem. 1997, 62, 4650. (Sm
and THF, then 1,2-diiodoethane added) (b) Reisman, S. E.; Ready, J.
M.; Weiss, M. M.; Hasuoka, A.; Hirata, M.; Tamaki, K.; Ovaska, T. V.;
Smith, C. J.; Wood, J. L. J. Am. Chem. Soc. 2008, 130, 2087. (Sm, then
1,2-diiodoethane in THF added) (c) Williams, D. R.; Berliner, M. A.;
Stroup, B. W.; Nag, P. P.; Clark, M. P. Org. Lett. 2005, 7, 4099.
(35) Baker, K. V.; Brown, J. M.; Hughes, N.; Skarnulis, A. J.; Sexton,
A. J. Org. Chem. 1991, 56, 698.
(36) Furstner, A. Active Metals. Preparation, Characterization,
̈
Applications. VCH: Weinheim: 1996.
(37) (a) Deacon, G. B.; Forsyth, C. M. Chem. Lett. 1989, 837.
(b) Lautens, M.; Ren, Y. J. Org. Chem. 1996, 61, 2210. (c) Garizi, N.
V., Ph.D. Thesis, The University of Texas, Austin, 2008. (d) Fukuzawa,
S.; Niimoto, Y.; Fujinami, T.; Sakai, S. Heteroatom. Chem. 1990, 1, 491.
(38) A common approach to increase the surface area of a metal
involves metal grinding under an inert atmosphere. However, this
method of activation of samarium metal would need to be carried out
in a glovebox and would be far less user-friendly than dry-stirring.
(39) For a list of methods that have been used to activate samarium
metal, see: Talukdar, S.; Fang, J. M. J. Org. Chem. 2001, 66, 330.
(40) To find out whether a particular batch of samarium metal is
likely to be “active” or “inactive” for the preparation of SmI2, charge a
four-dram vial with approximately 5 g of samarium metal and measure
the height of samarium metal in the vial. Calculate the apparent
volume of the vial occupied by the metal using the diameter of the vial
and the height of the samarium metal. Divide the mass of the metal by
the volume occupied in the vial to arrive at a measurement in the units
of density. The following values should serve as good guidelines for the
relationship between this measurement and the metal’s likely efficacy
in SmI2 preparation: “active” batches, 1.10−1.37 g/mL; “inactive”
batches, 3.67−4.40 g/mL.
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