Determination of the effective redox potentials of SmI2, SmBr2, SmCl2, and their complexes with water by reduction of aromatic hydrocarbons. Reduction of anthracene and stilbene by samarium(II) iodide-water complex

Article abstract of DOI:10.1021/jo4028243

Samarium(II) iodide-water complexes are ideally suited to mediate challenging electron transfer reactions, yet the effective redox potential of these powerful reductants has not been determined. Herein, we report an examination of the reactivity of SmI₂(H₂O)_n with a series of unsaturated hydrocarbons and alkyl halides with reduction potentials ranging from -1.6 to -3.4 V vs SCE. We found that SmI ₂(H₂O)_n reacts with substrates that have reduction potentials more positive than -2.21 V vs SCE, which is much higher than the thermodynamic redox potential of SmI₂(H₂O) _n determined by electrochemical methods (up to -1.3 V vs SCE). Determination of the effective redox potential demonstrates that coordination of water to SmI₂ increases the effective reducing power of Sm(II) by more than 0.4 V. We demonstrate that complexes of SmI₂(H ₂O)_n arising from the addition of large amounts of H ₂O (500 equiv) are much less reactive toward reduction of aromatic hydrocarbons than complexes of SmI₂(H₂O)_n prepared using 50 equiv of H₂O. We also report that SmI ₂(H₂O)_n cleanly mediates Birch reductions of substrates bearing at least two aromatic rings in excellent yields, at room temperature, under very mild reaction conditions, and with selectivity that is not attainable by other single electron transfer reductants.

Full text of DOI:10.1021/jo4028243

Article
pubs.acs.org/joc
Determination of the Effective Redox Potentials of SmI2, SmBr2,
SmCl2, and their Complexes with Water by Reduction of Aromatic
Hydrocarbons. Reduction of Anthracene and Stilbene by
Samarium(II) Iodide−Water Complex
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−water complexes are ideally suited to mediate challenging electron transfer reactions, yet
the effective redox potential of these powerful reductants has not been determined. Herein, we report an examination of the
reactivity of SmI2(H2O)n with a series of unsaturated hydrocarbons and alkyl halides with reduction potentials ranging from −1.6
to −3.4 V vs SCE. We found that SmI2(H2O)n reacts with substrates that have reduction potentials more positive than −2.21 V
vs SCE, which is much higher than the thermodynamic redox potential of SmI2(H2O)n determined by electrochemical methods
(up to −1.3 V vs SCE). Determination of the effective redox potential demonstrates that coordination of water to SmI2 increases
the effective reducing power of Sm(II) by more than 0.4 V. We demonstrate that complexes of SmI2(H2O)n arising from the
addition of large amounts of H2O (500 equiv) are much less reactive toward reduction of aromatic hydrocarbons than complexes
of SmI2(H2O)n prepared using 50 equiv of H2O. We also report that SmI2(H2O)n cleanly mediates Birch reductions of substrates
bearing at least two aromatic rings in excellent yields, at room temperature, under very mild reaction conditions, and with
selectivity that is not attainable by other single electron transfer reductants.
INTRODUCTION
■
Since its discovery in 1977 by Kagan,1 SmI2 (samarium(II)
iodide, Kagan’s reagent) has gained status as one of the most
important single electron transfer reagents in organic
chemistry.2 Of particular importance is the exquisite ability of
SmI2 to mediate reductive processes via complementary one-
and two-electron pathways with chemoselectivity that cannot
be achieved by other reagents.3,4 Crucial to the successful use of
SmI2 in numerous synthetic methodologies and target oriented
syntheses is the role of additives that modulate the steric
requirements and redox potential of the reagent by
coordination to the lanthanide(II) center, thus allowing users
to fine-tune the properties of SmI2 for a desired transformation
(Figure 1).5 In this regard, during the past decade, SmI2(H2O)n
complexes have received increasing attention as unique Sm(II)
reagents capable of mediating challenging reductive processes
that for years had been thought to lie outside the redox
potential of SmI2.6 However, despite several reports on the role
of H2O as a ligand for Sm(II),7 mechanistic details pertaining to
the effective redox potential of these powerful reductants have
not been investigated, hampering the development of new
chemoselective reactions mediated by SmI2(H2O)n and
prohibiting the rational design of ligands that would expand
Figure 1. Redox potentials of common Sm(II) reductants (SCE =
saturated calomel electrode).
the chemoselectivity of Sm(II) for a broad range of functional
groups.8
In general, the reactivity of Sm(II) reductants has been found
to correlate with the thermodynamic redox potentials as
determined by electrochemical methods (Table 1). The
seminal studies by Flowers9 and Skrydstrup10 demonstrated
that addition of 4 equiv of HMPA results in an increase of the
redox potential of SmI2 by ca. 0.90 V (Table 1, entries 1 and 2),
affording one of the most powerful reductants in organic
synthesis. Due to the high redox potential, SmI2−HMPA
Received: December 19, 2013
Published: February 11, 2014
© 2014 American Chemical Society
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Table 1. Summary of Redox Potentials of Common Sm(II) Reductants Determined by Electrochemical Methods
a
entry
Sm(II) reductant
SmI2
−E1/2
electrode
solvent
THF
refs
b
1
2
3
4
5
6
7
8
9
0.89 0.08
1.79 0.08
1.61 0.01
1.55 0.07
1.78 0.10
SCE
SCE
SCE
SCE
SCE
SCE
SCE
SCE
SCE
9, 10
9, 10
12
SmI2−HMPA
SmI2−DMPU
SmBr2
THF
c
THF
d
e
THF
14b
14b
18
SmCl2
THF
f
Sm(HMDS)2
SmBr2−HMPA
SmI2(H2O)n (n = 60)
SmI2(H2O)n (n = 500)
1.5 0.1
THF
g
2.03 0.01
THF
19
h
1.0 0.1
THF/DME
THF/DME
7a
i
1.3 0.1
7a
a
In volts vs SCE. −E1/2 describes the half-reduction potential measured in DMF, refs 20−23. (The accuracy is approximately 0.1 V due to solvent
b
c
effects.) Recalculated from −1.41 0.08 vs Fe+/Fe according to ref 23. Recalculated from −2.21 0.01 vs Ag/AgNO3; the difference between the
d
SCE and Ag/AgNO3 is 0.6 V, ref 12b. Note that the value based on ref 14a, recalculated from −1.98 0.01 vs Ag/AgNO3, is −1.38 0.01 vs SCE.
e
f
Note that the value based on ref 14a, recalculated from −2.11 0.01 vs Ag/AgNO3, is −1.51 0.01 vs SCE. Recalculated from −2.1 0.1 vs Ag/
g
h
i
AgNO3. Recalculated from −2.63 0.01 vs Ag/AgNO3. Recalculated from −1.6 0.1 vs Ag/AgNO3. Recalculated from −1.9 0.1 vs Ag/
AgNO3.
complexes have found diverse applications in Barbier reactions
and reductive cross-couplings utilizing unactivated π-accept-
ors.11 The addition of other Lewis bases (e.g., 1,3-dimethyl-
3,4,5,6-tetrahydro-2-pyrimidinone (DMPU), N-methyl-2-pyrro-
lidone (NMP), 2,2,6,6-tetramethylpiperidine (TMP), tripyrro-
lidino-phosphoric acid triamide (TPPA)) has been reported to
increase the thermodynamic redox potential of SmI2 (Table 1,
entry 3);12 however, despite significant progress in this area,13
HMPA is currently the most effective Lewis basic additive for
SmI2. Furthermore, Flowers has shown that the addition of 12
equiv of metal salts, LiBr or LiCl, to SmI2 results in the
formation of soluble Sm(II) reductants characterized by redox
potential much higher than that of the parent reagent (Table 1,
entries 4 and 5).14 UV−vis experiments demonstrated that this
reagent combination is equivalent to the less soluble SmBr2 and
SmCl2 prepared by independent methods by the reduction of
Table 2. Summary of Redox Potentials of Common Ln(II)
Reductants Determined by Reduction of Aromatic
Hydrocarbons
a
entry
Ln(II) reductant
−E1/2
electrode
solvent
ref
1
2
3
4
5
6
7
Sm metal
2.02
2.44
2.22
2.00
2.30
2.80
2.65
SCE
SCE
SCE
SCE
SCE
SCE
SCE
DME
DME
toluene
THF
THF
THF
THF
20
20
21
22
23
23
24
Yb metal
Sm(C5Me5)2
TmI2(THF)n
YbI2−amine−H2O
SmI2−amine−H2O
TmI2(MeOH)n
a
In volts vs SCE. −E1/2 describes the half-reduction potential
measured in DMF, refs 20−23. (The accuracy is approximately
0.1 V due to solvent effects.)
of the strongest lanthanide(II) reductants reported to date
(Table 2, entry 3),21 Fedushkin evaluated the reducing power
of TmI2 (Table 2, entry 4),22 Hilmersson determined the redox
potential of the powerful SmI2−amine−H2O and YbI2−amine−
H2O systems (Table 2, entries 5 and 6),23 and we have utilized
this method to show that the reagent formed by complexation
of MeOH to TmI2 is characterized by a much higher redox
potential than the parent lanthanide(II) iodide (Table 2, entry
7).24 Importantly, since only simple unsaturated hydrocarbons,
which react via a well-established, outer-sphere electron transfer
mechanism, are used,8,14b,18,23 these methods provide a robust
and practical evaluation of the effective reducing power of a
given lanthanide reductant under standard laboratory reaction
conditions, thus allowing definition of a practical reactivity scale
in an assay independent of the thermodynamic redox potential
measurements.
16
17
SmX3.15 Recently, SmBr2 and SmCl2 reductants have been
applied to achieve cross-coupling reactions of carbonyl
precursors in complex settings. The thermodynamic redox
18
potentials of SmI2(HMDS)2 and SmBr2−HMPA19 have also
been reported (Table 1, entries 6 and 7) and, as expected, are
much higher than those of SmI2 and SmI2−HMPA,
respectively. Finally, in 2004, Flowers reported a seminal
study on the thermodynamic redox potential of SmI2(H2O)n
(Table 1, entries 8 and 9).7b It was found that the addition of
60 equiv of water with respect to SmI2 results in an increase of
redox potential of SmI2 by ca. 0.10 V. The addition of 500
equiv of water resulted in the formation of a thermodynamically
more powerful reductant (redox potential of 1.3 V vs SCE).
Further addition of water had no additional impact on the
redox potential of the reagent.
Studies on the determination of the effective redox potential
of lanthanide reductants have also been reported (Table
2).20−24 These methods utilize the reduction of a series of
aromatic hydrocarbons with gradually increasing redox
potentials to correlate the reactivity of a lanthanide reductant
with the reduction potential of hydrocarbons. This indirect
determination of the redox potential is particularly useful in
cases of limited solubility, irreversible oxidation, precipitation,
and/or instability of lanthanide reductants under the conditions
of cyclic voltammetry studies. More specifically, Chauvin
determined the effective redox potential of several lantha-
nides(0) (Ce, Nd, Sm, Yb) (Table 2, entries 1 and 2),20 Evans
demonstrated that decamethylsamarocene, Sm(C5Me5)2, is one
Our laboratory has pioneered the use of SmI2(H2O)n
complexes to expand the reactivity of SmI2 toward carbonyl
functional groups traditionally thought to lie outside the
reducing range of Kagan’s reagent (Scheme 2).25−27 In
particular, we reported that activation of SmI2 with water
permits a fully chemoselective reduction of six-membered
lactones over other classes of lactones and esters (Scheme
2A).25a−c Moreover, we exploited the SmI2(H2O)n reagent to
develop the first chemoselective monoreduction of cyclic
diesters (Meldrum’s acids) to afford the valuable β-hydroxy
acid building blocks in a single transformation (Scheme 2B).26
Recently, we utilized the unusual ketyl-type radical inter-
mediates formed in SmI2(H2O)n-mediated electron transfer to
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lactone carbonyls as precursors in complex cyclization and
cyclization cascade processes to form polyoxygenated azulene
motifs (Scheme 2C).25c,d We have also established that water
serves a critical role with Sm(II) in the first general reductions
of unactivated aliphatic esters, acids, and lactones with SmI2,
which proceed via acyl-type radical intermediates generated
directly from the carboxylic acid derived functional groups.27
These processes have resulted in very significant expansion of
the synthetic scope of processes mediated by SmI2.28 A subtle
feature of all of these reactions is that water serves as a unique
additive for SmI2; no reaction occurs with SmI2 alone or with a
variety of other additives (e.g., HMPA, DMPU, LiCl), which
have been shown to form more thermodynamically powerful
complexes with SmI2 than SmI2(H2O)n (Table 1). Further-
more, we established that no reaction occurs at low
concentration of water, which rules out the role of water as a
proton donor placed in a close proximity to the radical anion
after the electron transfer step.29
Moreover, we describe herein the synthesis and determi-
nation of the effective redox potential of several reductants
related to SmI2, namely, SmX2 and SmX2(H2O)n (X = Cl,
Br),16,17 which allows us to delineate the reducing power of
these popular Sm(II) reductants for the first time. Furthermore,
as a result of this investigation, we report that SmI2(H2O)n
cleanly mediates Birch reduction33 of substrates with at least
two aromatic rings in excellent yields, at room temperature,
under very mild reaction conditions, and with selectivity that is
not attainable by other single electron transfer reductants.3,4
Finally, we provide mechanistic studies into the role of electron
transfer from Sm(II) and discuss the implications of the
effective redox potentials as determined in this study for using
SmX2 and SmX2(H2O)n complexes in organic synthesis. This
study provides the first set of guidelines with respect to
reducing power to further our understanding of single electron
transfer processes mediated by the extremely useful Sm(II)-
based reductants.
RESULTS AND DISCUSSION
■
To determine the effective redox potential of SmI2(H2O)n
complexes, we selected a series of aromatic hydrocarbons with
reduction potentials ranging from −1.6 to −3.4 V vs SCE
(Figure 3).20−24 In addition, a series of alkyl halides (E1/2 from
Figure 2. Recent applications of SmI2(H2O)n in chemoselective and
stereoselective synthesis: (A) reduction of six-membered lactones; (B)
monoreduction of Meldrum’s acids; (C) cyclization cascades of
lactones.
Figure 3. Structures of aromatic hydrocarbons and alkyl halides used
in this study together with their half-reduction potentials (E1/2 in volts
in DMF vs SCE).
On the basis of our extensive experience in the reductive
chemistry of lanthanides(II), we considered that the reduction
of lactone carbonyls (E1/2 = ca. −3.0 V vs SCE)30 by
SmI2(H2O)n (E1/2 = ca. −1.3 V vs SCE)7b is inconsistent with
the thermodynamic redox potential of SmI2(H2O)n as
determined by cyclic voltammetry studies and cannot be
explained exclusively by electrostatic interaction31 between the
lactone carbonyl groups and the Lewis acidic Sm(II) center.32
To understand in more detail the properties of SmI2(H2O)n
reductants, we determined the effective redox potential of these
reagents by examining the reactivity of SmI2(H2O)n complexes
with a series of unsaturated hydrocarbons and alkyl halides with
reduction potentials ranging from −1.6 to −3.4 V vs SCE.
Remarkably, we found that SmI2(H2O)n reacts with substrates
which have reduction potentials more positive than −2.21 V vs
SCE, which is much higher than the thermodynamic redox
potential of SmI2(H2O)n determined by electrochemical
methods (up to −1.3 V vs SCE).7b Moreover, in contrast to
literature, we demonstrated that complexes of SmI2(H2O)n in
which n = 500 are much less reactive toward aromatic
hydrocarbons than complexes of SmI2(H2O)n based on n = 50.7
This has important practical implications for using SmI2(H2O)n
reagents in organic synthesis.
−1.30 to −3.0 V)34 was selected for this study to gain further
insight into the chemoselectivity of SmI2(H2O)n mediated
reactions. These substrates are well-established to react via an
outer-sphere mechanism10a,14b,18,23,28o,p and should provide
complementary information on the effective reducing power of
SmI2(H2O)n to the reactions with a set of aromatic hydro-
carbons.
We started our investigation by studying in detail the
reduction of aromatic hydrocarbons using SmI2(H2O)n
complexes in which n = 50 and n = 500 with respect to SmI2
because these complexes have been shown previously to be
more thermodynamically powerful than the parent SmI2 (Table
3).7b In order to determine the increase of effective redox
potential upon coordination of H2O to Sm(II), the reduction
by SmI2 in THF was chosen as a benchmark. For comparison,
all runs were performed in parallel, using stock solutions of
SmI2 prepared immediately prior to use35 and titrated
according to the established methods to determine the molarity
of the active Sm(II) reductant.35d,e All reactions were
performed with 3 equiv of Sm(II) reductant (1.5 molar
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Table 3. Determination of Redox Potential of SmI2(H2O)n by Reduction of Aromatic Hydrocarbons
reaction with SmI2(H2O)n
a
entry
hydrocarbon
−E1/2
reaction with SmI2
n = 50
n = 500
1
2
acenaphthylene
cyclooctatetraene
anthracene
1.65
1.83
1.98
2.11
2.21
2.40
2.51
2.61
2.65
3.42
52.6 (6 h)
>98 (6 h)
<2 (6 h)
<2 (6 h)
0.8 (5 h)
<2 (5 h)
<2 (5 h)
<2 (4 h)
<2 (4 h)
<2 (4 h)
73.4 (22 min)
>98 (21 min)
93.2 (37 min)
51.9 (16 min)
>98 (9 min)
86.8 (6 min)
<2 (48 min)
4.9 (20 min)
<2 (11 min)
<2 (24 min)
<2 (2 h)
3
b
4
diphenylacetylene
stilbene
0.9 (2 h)
5
53.1 (2 h)
<2 (2 h)
<2 (2 h)
<2 (2 h)
1.3 (2 h)
<2 (2 h)
6
1,4-diphenylbenzene
1,3,5-triphenylbenzene
naphthalene
7
8
9
styrene
0.5 (2 h)
10
benzene
<2 (2 h)
a
1
In volts vs SCE; −E1/2 describes half-reduction potential, refs 20−23. Columns 4−6 refer to conversions in %, determined by GC or H NMR.
Conditions: 0.05 mmol of substrate, 3 equiv of SmI2. All reactions quenched with air after the indicated time. In cases when time is <2 h,
SmI2(H2O)n complexes were oxidized by excess of water to Sm(III). 0.4% bibenzyl and 0.5% stilbene. In cases when conversion is <2%, only
b
starting material was detected in the reaction mixtures.
equiv, 2 equiv required for the reduction of a π-bond) using
preformed SmI2(H2O)n complexes. To identify the increase of
effective redox potential, all benchmark reactions using
solutions of SmI2 were quenched with air after 4−6 h (the
natural decay of SmI2 is 4.4 × 10−4 s−1),36 while the reactions
using SmI2(H2O)n were allowed to stir for 2 h or quenched
with air when decolorization from burgundy red to white or
transparent occurred earlier.7b,c At this stage no effort was made
to optimize the reactions to completion (vide infra); the focus
was placed on the determination of the effective redox potential
based on the well-established premise that the reduction of
aromatic hydrocarbons correlates with the redox potential of
the lanthanide.
Reduction of Aromatic Hydrocarbons. The results of
the initial investigation are listed in Table 3. From comparison
of the results it is clear that the addition of water has a
profound effect on the effective redox potential of SmI2. Most
remarkably, the system consisting of SmI2(H2O)n is capable of
reducing trans-stilbene (E1/2 = −2.21 V, all values vs SCE),
while under the same conditions SmI2 in THF is unreactive.
lanthanide(II) reductants in reactions with aromatic hydro-
carbons has been previously reported and is in line with the
relative stability of these systems as observed in the current
study.37 We also note that although unsaturated hydrocarbons
have been suggested to react with lanthanides(II) via an outer-
sphere electron transfer, organometallic complexes of SmI2 with
cyclooctatetraene have been reported.22 Moreover, the relative
lack of reactivity of diphenylacetylene (E1/2 = −2.11 V, cf.
stilbene) with SmI2(H2O)n might be indicative of inner-sphere
character in the reduction of aromatic hydrocarbons with
SmI2(H2O)n (vide infra). In summary, results presented in
Table 3 provide strong independent evidence that the effective
reducing power of SmI2(H2O)n is at least 0.9 V higher than that
obtained by ground state measurements7b and show that there
is a significant effect of the coordination of water on the redox
potential of Sm(II) reagent.
Reduction of Alkyl Halides. In order to gain further
insight into the effective redox potential of SmI2(H2O)n, we
examined the reduction of alkyl halides with increasing redox
potentials using SmI2(H2O)n (Table 4). These reactions were
Interestingly, all three systems reduce acenaphthylene (E1/2
=
Table 4. Determination of Redox Potential of SmI2(H2O)n
by Reduction of Alkyl Halides
−1.65 V) and cyclooctatetraene (E1/2 = −1.83 V), while no
reaction is observed with aromatic hydrocarbons with redox
potential more negative than −1.83 and −2.21 V for SmI2 and
SmI2(H2O)n reductants, respectively. Moreover, SmI2(H2O)n
complexes reduce anthracene (E1/2 = −1.98 V), with an
efficiency slightly higher than that of stilbene, as is expected
from the relative redox potentials of these substrates.
Furthermore, the reactivity of SmI2(H2O)n n = 500 is lower
than that of SmI2(H2O)n n = 50, in contrast to the
thermodynamic redox potentials of these Sm(II) systems as
determined by cyclic voltammetry measurements.7b
Overall, the results presented in Table 3 establish that (1) the
effective redox potential of SmI2(H2O)n complexes for the
reduction of aromatic hydrocarbons is in the range of ca. −2.2
V vs SCE; (2) the SmI2(H2O)n system with n = 500 performs
less efficiently than the system comprising n = 50 of water; and
(3) the effective redox potential of SmI2 is much higher than its
thermodynamic redox potential (see Table 1). From the
mechanistic standpoint, we propose that the increased reactivity
of SmI2(H2O)n complex n = 50 over n = 500 results from
saturation of the coordination sphere of Sm(II) center at high
concentration of water;7c however, lower stability of the latter
system cannot be excluded at this point. Indeed, oxidation of
reaction with SmI2(H2O)n
reaction with
a
c
c
c
entry alkyl halide −E1/2
SmI2
(n = 50)
(n = 500)
1
2
3
4
C12H25I
1.30
2.29
2.79
4.6 (2 h)
14.2 (2 h)
2.3 (2 h)
<2 (2 h)
94.0 (2 h) 90.7 (2 h)
50.6 (2 h) 41.9 (2 h)
C14H29Br
C14H29Cl
C14H29F
<2 (2 h)
<2 (2 h)
<2 (2 h)
<2 (35 min)
b
3.0
a
In volts vs SCE; −E1/2 describes half-reduction potential. Columns
b
4−6 refer to conversions in %. Determined for ArF, ref 34.
c
1
Determined by GC or H NMR.
performed under the conditions outlined above for Table 3.
Likewise, the results in Table 4 reveal that the addition of water
to SmI2 results in the formation of a much stronger reductant,
capable of efficiently reducing an alkyl iodide and bromide
(Table 4, entries 1 and 2). Remarkably, the reaction is not
observed when alkyl chloride or fluoride are exposed to
SmI2(H2O)n (Table 4, entries 3 and 4), which defines the
reactivity of the SmI2(H2O)n reagent toward reduction of alkyl
halides and explains the excellent chemoselectivity of this
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Article
reagent reported in our previous studies.25−27 Finally, SmI2 in
THF (3 equiv, rt, 3 h) does not reduce an alkyl iodide and
bromide to a significant extent, highlighting the preference of
the reagent for an inner-sphere electron transfer and consistent
with literature reports.2,3 Overall, the results presented in Table
4 demonstrate that (1) activation of SmI2 with H2O affords a
much stronger reductant; and (2) the effective redox potential
of SmI2(H2O)n determined in the reduction of alkyl halides of
ca. −2.3 V is in very good agreement with the reduction of
stilbene (E1/2 = −2.21 V) by SmI2(H2O)n complexes.
Optimization of the Reduction of Anthracene and
trans-Stilbene. Having determined that SmI2(H2O)n com-
plexes are capable of reducing aromatic hydrocarbons with
redox potentials up to −2.21 V vs SCE, we next turned our
attention to examining in more detail the reduction of
anthracene and stilbene with SmI2(H2O)n. The results of the
optimization of the reduction of anthracene are presented in
Table 5. First, we determined that the addition of as little as 3
Table 6. Optimization of the Reduction of Stilbene with
SmI2(H2O)n
a
entry stilbene SmI2 (equiv) H2O (equiv/SmI2)
time
conv (%)
b
1
2
3
4
5
6
7
8
9
E
E
E
E
E
E
E
E
Z
Z
E
E
E
E
3
3
−
25
50
−
10
25
50
100
25
50
25
50
50
100
5 h
2 h
2 h
24 h
24 h
2 h
2 h
2 h
2 h
2 h
3 h
3 h
2 h
2 h
0.8
20.7
53.1
0.8
b
3
6
6
2.4
6
37.5
47.0
40.0
3.9
6
6
6
10
11
12
13
14
6
14.7
35.1
75.0
74.9
10
10
3
c
c
Table 5. Optimization of the Reduction of Anthracene with
SmI2(H2O)n
3
92.7
a
b
c
1
Determined by GC or H NMR. Reproduced from Table 1. Two
iterations (sequential reactions). Conditions: 0.05 mmol of substrate, 3
equiv of SmI2. In all entries, >95% yield based on recovered starting
material. Entry 13, 57.5% conv after first iteration; entry 14, 56.9%.
a
entry
SmI2 (equiv)
H2O (equiv/SmI2)
time
conv (%)
b
achieved when ca. 50 equiv of water is used to preform the
SmI2(H2O)n reagent, in line with the findings on the reduction
of anthracene using SmI2(H2O)n. We determined that the
optimum results in terms of the reaction rate and efficiency are
obtained by carrying out the reaction in two iterations, which
might be indicative of the substrate displacement from the
coordination sphere of Sm(II). Interestingly, the reduction of
cis-stilbene with SmI2(H2O)n performed under the same
reaction conditions was found to be much slower than that
of trans-stilbene. In addition, no isomerization of cis-stilbene to
the trans-isomer was observed in the unreacted staring material,
which suggests that the first electron transfer step is irreversible
in the reduction of this substrate.
Initial Studies on the Mechanism. Several experiments
were performed to gain preliminary insight into the mechanism
of the reduction of anthracene and stilbene with SmI2(H2O)n.
First, determination of the deuterium incorporation and kinetic
isotope effect in the reduction of anthracene (Scheme 1) and
trans-stilbene (Scheme 2) demonstrate that anions are
generated and protonated by H2O in a series of single electron
1
3
3
3
3
3
6
6
6
3
3
−
3.3
−
50
500
−
10
50
10
50
2 h
2 h
<2
b
2
8.2
c
3
6 h
<2
c
4
37 min
6 min
24 h
24 h
2 h
93.2
c
5
86.8
6
<2
7
99.5 (98)
>98 (99)
67.6 (67)
>98 (99)
8
9
2 h
10
2 h
a
Determined by GC or 1H NMR. All reactions quenched with air after
the indicated time. In cases when time is <2 h, SmI2(H2O)n complexes
were oxidized by excess of water to Sm(III). Side-by-side reactions.
b
c
Reproduced from Table 1. Conditions: 0.05 mmol of substrate, 3
equiv of SmI2. Yield (1H NMR) in brackets.
equiv of water to SmI2 results in the activation of SmI2 toward
the reduction (Table 5, entries 1 and 2). Extended reaction
time had no impact on the reactivity of SmI2, which is
consistent with the limiting redox potential of the unactivated
SmI2(THF)n toward the reduction of anthracene (entry 6).
Next, we found that the addition of 10 equiv of water to SmI2
affords the reduction product in an excellent yield; however, the
reaction rate was faster when SmI2(H2O)n was preformed using
50 equiv of water, consistent with the activation of lanthanide
by H2O (entries 7 and 8). Finally, we found that the
stoichiometry of SmI2 could be decreased to 3 equiv (1.5
mmol equiv), with 50 equiv of H2O providing the best results
in terms of reaction efficiency and time (entry 10).
Scheme 1. Determination of Deuterium Incorporation and
Kinetic Isotope Effect in the Reduction of Anthracene with
SmI2(H2O)n
Table 6 summarizes the results of optimization of the
reduction of trans-stilbene using SmI2(H2O)n. As expected from
the relative redox potentials, the reduction of stilbene is more
challenging than the reduction of anthracene. The results in
Table 6 demonstrate that the activation of SmI2 with water is
required for the reduction (<2.0% conversion using
SmI2(THF)n complex) and that the maximum reactivity is
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Scheme 2. Determination of Deuterium Incorporation and
Kinetic Isotope Effect in the Reduction of Stilbene with
SmI2(H2O)n
Table 7. Effect of SmI2 Source on the Reduction of Stilbene
with SmI2(H2O)n
a
SmI2
(equiv)
H2O
(equiv/SmI2)
conv
(%)
entry
time
SmI2 source
b
1
3
3
50
50
2 h
53.1
stock solution
d
2
10 min
15.7
in situ
solution
c
d
3
3
50
30 min
15.0
powder
a
b
c
1
Determined by GC or H NMR. Reproduced from Table 3. SmI2
powder (AAPL) was used. Conditions: 0.05 mmol of substrate, 3
d
equiv of SmI2. 15% yield.
transfer steps25 and that the proton transfer is not involved in
the rate determining step of the reaction.38 Next, the relative
reactivity of SmI2(H2O)n towards cis- and trans-stilbene was
determined by performing intermolecular competition experi-
ments. This demonstrated that under these reaction conditions
trans-stilbene is 3.5 times more reactive than the cis-isomer
(Scheme 3).39 Thus, the relative reactivity of aromatic
maximum reactivity with SmI2(H2O)n complexes, homoge-
neous stock solutions of SmI2 in THF should be used while
taking all precautions outlined in our previous study to avoid
contamination of the reagent with Sm metal and Sm(III)
iodide.41
Reductions Using SmI2(MeOH)n. In addition to water,
methanol has emerged as one of the most popular proton
donor additives for SmI2.2,3 Although it has been proposed that
the increased reactivity of SmI2(MeOH)n might originate from
the higher redox potential of the reagent (vs SmI2(THF)n),29c
the effective reducing power of SmI2(MeOH)n has not been
elucidated.
Scheme 3. Determination of Relative Rates of the Reduction
of E- and Z-Stilbene with SmI2(H2O)n
To determine the redox potential of SmI2(MeOH)n
complexes, we investigated the reactivity of SmI2(MeOH)n in
the reduction of aromatic hydrocarbons (Table 8). For these
substrates decreases in order anthracene (not shown) > (E)-
stilbene > (Z)-stilbene > diphenylacetylene (eq 1), which we
Table 8. Reduction of Aromatic Hydrocarbons with
SmI2(MeOH)n Complexes (n = 150)
MeOH
SmI2
−E1/2 (equiv)
(equiv,
conv
b
a
entry
hydrocarbon
4:1 v/v)
time (%)
ascribe to a combination of two factors: (a) the relative redox
potentials of the substrates; and (b) the ease of coordination of
a π-system to the SmI2 reductant (cf. stilbene isomers). The
lower reactivity of cis-stilbene may be due to reduced
conjugation because of steric hindrance. Taken together,
these results strongly suggest that the electron transfer from
Sm(II) to some of the aromatic substrates occurs through
electron transfer with inner-sphere character, which would
explain the dramatic difference between the thermodynamic
and effective redox potentials of SmI2(H2O)n reductants.
Source of SmI2. We recently reported a detailed
investigation on the preparation of SmI2.35a In particular, we
demonstrated that the degree of dispersion of Sm metal and
homogeneity of SmI2 solutions can have a profound influence
on the reactivity of the Sm(II) reagent. To determine the
impact of residual Sm metal on the reactivity of SmI2(H2O)n
solutions, we evaluated the reduction of trans-stilbene using
SmI2 prepared by different methods (Table 7). Under typical
conditions, using stock solutions of SmI2 in THF and taking all
precautions to ensure homogeneity of the reagent, SmI2(H2O)n
exhibits good stability (see Experimental Section for stability
studies), resulting in the efficient reduction of trans-stilbene
(Table 7, entry 1). In contrast, the use of SmI2 powder or SmI2
solutions prepared in situ (i.e., containing residual Sm metal)
leads to much lower conversions due to decay of the reagent by
formation of mixed samarium hydroxides as the major
decomposition pathway.40 We note that this is an important
practical consideration and recommend that in order to achieve
1
2
3
acenaphthylene
anthracene
stilbene
1.65
1.98
2.21
3
3
3
275
275
275
1 h
2 h
2 h
9.1
2.0
1.1
a
In volts vs SCE; -E1/2 describes half-reduction potential, ref 20−23.
All conversions determined by GC or H NMR. Conditions: 0.05
b
1
mmol of substrate, 3 equiv of SmI2. All reactions quenched with air
after the indicated time.
experiments the stoichiometry of MeOH most commonly cited
in the literature (i.e., 4:1 v/v w/THF)2,3 was employed. The
results in Table 8 indicate that the effective redox potential of
SmI2(MeOH)n is much lower than that of SmI2(H2O)n
complexes. Moreover, SmI2(MeOH)n shows reduced reactivity
toward acenaphthylene (Table 8, entry 1) compared with that
of SmI2(THF)n (Table 3, entry 1). These results suggest that
the beneficial role of MeOH in SmI2-mediated reactions does
not involve changes in the redox potential of the reagent.
Furthermore, the lower reactivity of acenaphthylene with
SmI2(MeOH)n supports inner-sphere electron transfer charac-
teristics in the reduction of aromatic hydrocarbons with
SmI2.7,29
Determination of the Effective Redox Potential of
SmBr2, SmCl2, SmBr2(H2O)n, and SmCl2(H2O)n. In the past
decade, samarium(II) bromide and samarium(II) chloride have
seen increasing application as powerful samarium(II)-based
reductants.4d Specifically, SmBr2 and SmCl2 permit activation of
recalcitrant substrates toward electron transfer as a result of
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their much higher redox potential compared to SmI2.14
Moreover, due to the smaller radial size of the halide
counterions these Sm(II)-based reductants have been shown
to exhibit much higher selectivity than SmI2 in the reductive
coupling of carbonyl groups due to the enhanced inner-sphere
character of the electron transfer.16,17 The most popular
method for the synthesis of samarium(II) bromide and
samarium(II) chloride relies on counterion exchange from
the readily available solutions of SmI2 in THF and LiBr or LiCl
reported by Flowers.14
In light of the increasing importance of SmBr2 and SmCl2 in
organic synthesis, we considered that the determination of the
effective redox potential of these reductants could define the
functional group tolerance possible with Sm(II) reagents and
provide a practical reactivity scale allowing a direct comparison
with SmI2-based systems. From the outset of our studies, a
major objective was to prepare and determine the reactivity of
SmBr2(H2O)n and SmCl2(H2O)n complexes as more powerful
alternatives to SmI2(H2O)n systems with a long-term goal of
utilizing a family of easily tunable SmX2(H2O)n complexes for
chemoselective electron transfer reactions. Prior to this study,
the synthesis of SmBr2(H2O)n and SmCl2(H2O)n had not been
reported,42 and it was not certain if these complexes would be
sufficiently stable to permit reductions due to the much higher
thermodynamic redox potential of the parent lanthanide(II)
halide, which was expected to facilitate the irreversible
oxidation of Sm(II) to Sm(III).43
dark green; reminiscent of TmI2−THF complexes). The
addition of water (50 equiv with respect to SmX2; the most
reactive system as determined for SmI2) to the stock solutions
of SmX2 in THF resulted in a color change to dark red,
indicative of the formation of SmBr2(H2O)n and SmCl2(H2O)n
complexes. As expected from the relative redox potentials,
SmBr2(H2O)n and SmCl2(H2O)n proved to be more sensitive
to oxidation than the corresponding SmI2(H2O)n complex (t1/2
of SmBr2(H2O)n, ca. 10 min; SmCl2(H2O)n, ca. 2−3 min;
SmI2(H2O)n, more than 24 h. See Experimental Section for
details). We note that from a synthetic standpoint, the high
redox potential of SmX2 (X = Cl, Br) should compensate for
the lower stability of these systems.44
The results of determination of the effective redox potentials
of SmX2 (X = Cl, Br) and their complexes with water are
presented in Table 9. Most importantly, SmBr2 and SmCl2
alone are capable of reducing aromatic hydrocarbons with
redox potentials more positive than −2.2 V vs SCE, which is
much higher than the redox potentials determined by cyclic
voltammetry studies by ca. 0.4 V. Interestingly, the addition of
water does not result in a significant increase in the reactivity of
SmBr2 and SmCl2, which could be due to the formation of
more sterically encumbered reductants by coordination of
water (cf. SmI2).7c,d,14b,18 Importantly, aromatic hydrocarbons
with redox potential more negative than −2.2 V vs SCE are not
reduced by SmX2 and their complexes with water, which allows
to define the effective reducing power of these Sm(II)
reductants as ca. −2.2 V vs SCE.
The results of our investigation of the reactivity of SmX2 (X
= Cl, Br) and SmX2(H2O)n with a set of alkyl halides are
outlined in Table 10. Interestingly, both SmBr2 and SmCl2
exhibit higher reactivity toward an alkyl bromide than alkyl
iodide, whereas an alkyl chloride is tolerated by these
reductants. This trend of reactivity is presumably due to a
combination of two effects: (a) the redox potential of the
substrate; and (b) the ease of the inner-sphere electron transfer
process, in agreement with previous findings.14b Intriguingly, an
alkyl fluoride is a viable substrate for the reduction with SmBr2.
The increased reactivity of this substrate is most likely due to a
SN2-type displacement of fluoride by SmXBr2 (X = Br, OH)
with the resulting alkyl bromide being reduced. This mirrors
the recently reported activation of alkyl fluorides with YbI3.45
Unexpectedly, the addition of water has a deleterious effect
on the reduction of alkyl halides with SmBr2 and SmCl2 in most
cases examined. Since the solutions of SmBr2(H2O)n and
SmCl2(H2O)n were effective in reducing trans-stilbene with a
SmBr2 and SmCl2 (THF solution) reductants were prepared
by the addition of freshly prepared SmI2 solutions in THF to
the anhydrous LiBr or LiCl salts (Scheme 4). In agreement
Scheme 4. Preparation and Stability of SmX2 and
SmX2(H2O)n Complexes
with the literature, the counterion exchange was followed by
changes in color of the reaction mixtures (SmI2: dark blue;
SmBr2: violet, reminiscent of SmI2−HMPA complexes; SmCl2:
Table 9. Determination of Redox Potential of SmBr2, SmCl2, SmBr2(H2O)n, and SmCl2(H2O)n by Reduction of Aromatic
Hydrocarbons
a
b
b
b
b
entry
hydrocarbon
−E1/2
reaction with SmBr2
reaction with SmBr2(H2O)n
reaction with SmCl2
reaction with SmCl2(H2O)n
1
2
3
4
5
6
7
8
acenaphthylene
cyclooctatetraene
anthracene
1.65
1.83
1.98
2.11
2.21
2.40
2.65
3.42
15.3
>98
30.5
<2
12.2
>98
5.9
<2
9.8
>98
7.0
<2
7.1
>98
10.3
<2
diphenylacetylene
stilbene
20.0
<2
15.9
<2
16.5
<2
18.8
<2
1,4-diphenylbenzene
styrene
<2
<2
2.0
nd
0.4
benzene
<2
<2
nd
a
b
In volts vs SCE; −E1/2 describes half-reduction potential. Columns 4−7 refer to conversions in %. All conversions determined by GC or 1H NMR.
All reactions with SmCl2 or SmCl2(H2O)n 2−3 min until decolorization; SmBr2(H2O)n 2−3 min until decolorization; SmBr2: entry 1, rapid
decolorization to yellow; entries 2−6, 2−3 min until decolorization; entries 7−8, 2 h.
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Table 10. Determination of Redox Potential of SmBr2, SmCl2, SmBr2(H2O)n, and SmCl2(H2O)n by Reduction of Alkyl Halides
a
entry
alkyl halide
−E1/2
reaction with SmBr2
reaction with SmBr2(H2O)n
reaction with SmCl2
reaction with SmCl2(H2O)n
d
e
1
2
3
4
C10H21I
1.30
2.29
2.79
23.6 (2 h)
58.0 (2 h)
3.3 (2 h)
23.1 (3 min)
36.6 (3 min)
55.3 (3 min)
9.5 (3 min)
<2 (3 min)
C14H29Br
C14H29Cl
C14H29F
<2 (3 min)
1.7 (3 min)
21.2 (3 min)
1.8 (3 min)
<2 (3 min)
7.8 (3 min)
b
3.0
22.1 (15 min)
5.5 (3 min)
a
b
In volts vs SCE; −E1/2 describes half-reduction potential. Columns 4−7 refer to conversions in %. Determined for ArF, ref 34. All conversions
d
e
determined by GC or 1H NMR. 32.6/1 h. Average of two experiments (1.3, 2.3 conv). All reactions with SmCl2 or SmCl2(H2O)n 2−3 min until
decolorization; SmBr2(H2O)n 2−3 min until decolorization; SmBr2: entries 1−3 2 h; entry 4, 15 min until decolorization.
reaction rate similar to that of SmBr2 and SmCl2 (Table 9), we
postulate that the lower reactivity of SmBr2(H2O)n and
SmCl2(H2O)n in the reduction of alkyl halides results from
saturation of the coordination sphere of these Sm(II)
reductants.7c,18 Further studies are ongoing to determine the
role of water in the reduction of other functional groups and
reductive cross-couplings with SmBr2(H2O)n and
SmCl2(H2O)n complexes.
Reductions Using SmBr2 Prepared from 1,1,2,2-
Tetrabromoethane. It has been reported that solutions of
SmBr2 and SmCl2 prepared by counterion exchange from SmI2
often exhibit beneficial reactivity compared to that of SmBr2
and SmCl2 prepared by other methods due to the formation of
solvated monomers in the synthesis from SmI2.14b To probe
whether the selected method of preparation contributed to the
high reactivity of SmBr2 in the reduction of aromatic
hydrocarbons, we synthesized SmBr2 via an alternative
procedure from Sm metal and 1,1,2,2-tetrabromoethane
(Scheme 5).46 In agreement with previous reports, this method
Having determined that the readily available SmI2(H2O)n
system efficiently reduces aromatic hydrocarbons with redox
potentials more positive than −2.2 V vs SCE, we recognized
that this reagent would provide an attractive alternative to the
classic Birch reductions of substrates bearing at least two
aromatic rings. Towards this end, we subjected a broad range of
aromatic hydrocarbons with redox potentials higher than −2.2
V vs SCE to the SmI2(H2O)n reaction conditions. Table 11
shows the synthetic scope of Birch reductions mediated by the
SmI2(H2O)n reagent. In all cases examined the reactions are
high-yielding and proceed with excellent chemoselectivity; we
did not observe any products resulting from over-reduction
even in cases when large excess of the reagent was used.
Entries 1−4 demonstrate the reduction of anthracene and
tetracene derivatives. Interestingly, the reduction of 9,10-
diphenylanthracene (entry 3) furnishes the dearomatized
product with synthetically useful trans diastereoselectivity (dr
= 98:2), which compares favorably with other protocols (vide
infra).48a We note that several of these polycyclic dearomatized
products represent important structural motifs for applications
in materials chemistry, as semiconductors and optical devices.
Entries 5 and 6 show the reduction of conjugated alkenes. The
reduction of 9-(chloromethyl)anthracene (entry 7) demon-
strates the potential of the developed process to perform
reductions in tandem. Finally, we were pleased to find that this
protocol could be extended to unsaturated hydrocarbons
bearing carboxylic acid, ester, and amide functional groups
placed at the sensitive benzylic position,50,51 further high-
lighting the functional group tolerance of the reaction. At this
stage, N-containing heterocycles, such as acridine and quinoline
derivatives, are not efficient substrates,52 presumably due to
competing overreduction caused by the more positive
reduction potential and a change of mechanism to reversible
inner-sphere electron transfer by N-coordination.53 Despite this
limitation, we believe that the reaction should find useful
applications as an attractive room temperature alternative to the
classic Birch-type reductions using alkali metals in liquid
ammonia.33 Further studies on the reductive dearomatizing
cross-coupling of aromatic hydrocarbons using the SmI2(H2O)n
reagent are underway in our laboratories.
Scheme 5. Attempted Reduction of Stilbene using SmBr2
Prepared from Sm Metal and 1,1,2,2-Tetrabromoethane
afforded a slurry of SmBr2 in THF (in contrast to clear
solutions of SmBr2 obtained by counterion exchange).14b The
slurry of SmBr2 in THF as well as upon activation with water or
LiCl did not promote the reduction of stilbene (Scheme 5),
demonstrating that the procedure reported by Flowers is at
present the method of choice for the synthesis of active
solutions of SmBr2 and SmCl2.
Birch Reductions Using SmI2(H2O)n. Birch reductions
using alkali metals in liquid ammonia are among the most
important methods for dearomatization of feedstock aromatic
hydrocarbons; however, these procedures are inherently limited
by low functional group tolerance and require cryogenic
temperatures (NH3, bp = −33 °C), which complicates both
industrial and laboratory scale applications.33 Recent note-
worthy developments to expand the scope of classic Birch
reductions include ammonia-free reductions of electron-
deficient aromatics using LiDBB (lithium di-tert-butyl biphenyl)
in THF at −78 °C reported by Donohoe47 and room
temperature reductions of aromatic rings using alkali metals
in silica gel reported by Jackson and co-workers,48 among other
reports.49
Studies on the Origin of Selectivity. Several studies were
performed to gain insight into the reduction mechanism and to
understand the observed selectivity.
First, to illustrate the chemoselectivity observed with the
SmI2(H2O)n reagent, we have carried out a series of
competition experiments using substrates that are readily
reduced with single electron transfer reagents other than
SmI2(H2O)n (Table 12). In all cases, no reduction products
arising from naphthalene, an alkyl chloride and aryl bromide
were observed despite long reaction times and excess of the
reagent, while anthracene underwent smooth reduction in
excellent yield.
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Table 11. Birch Reductions of Aromatic Hydrocarbons Using SmI2(H2O)n Complexes
a
Determined by 1H NMR. In all entries, over-reduction was not detected by 1H NMR and GC−MS analysis of reaction mixtures. In addition, over-
b
c
d
reduction using large excess of SmI2/H2O (10−50 equiv) was not observed (entry 8). Isolated yield, 1.0 mmol scale. Conversion. Reaction using
SmI2 (3 equiv), H2O (24 equiv), and Et3N (24 equiv); 34% yield using SmI2/H2O (3−50, 2 h).
Table 12. Chemoselectivity in Birch Reductions of Aromatic Hydrocarbons using SmI2(H2O)n Complexes
a
Determined by GC−MS and 1H NMR. Reduction products from competition substrates 15 were <2% in all entries. Conditions: SmI2 (3 equiv),
H2O (50 equiv/SmI2), THF, rt, 1 h.
Next, to investigate the role of the protonation step, we
studied in detail deuterium incorporation in the reduction of
trans-stilbene and the stereoselectivity of protonation in the
reaction of 9,10-diphenylanthracene using SmI2(H2O)n and
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related SET reductants (Scheme 6). The reduction of trans-
stilbene with SmI2(D2O)n and with the more thermodynami-
strated that both classes of substrates (i.e., benzoic and
anthracene carboxylic acid derivatives) undergo instantaneous
reduction with SmI2(H2O)n (<30 s at room temperature).
Proposed Mechanism. On the basis of these studies, we
conclude that the reduction of aromatic hydrocarbons with
SmI2(H2O)n proceeds through the rate-determining first
electron transfer step to give the radical anion, which is then
protonated by H2O (Scheme 8). A second electron transfer
generates the anion, which is quenched by the water cosolvent.
This mechanism is different from the classic Birch reductions,
which have been shown to proceed via the rate-determining
protonation.54 We propose that the complete selectivity
observed in reductions of aromatic hydrocarbons with redox
potential more positive than −2.2 V vs SCE using SmI2(H2O)n
originates in the rate of the first electron-transfer step. Our
results suggest that the beneficial influence of water in these
reductions arises from the activation of the SmI2 reductant by
increasing its redox potential.7b Finally, although it has been
proposed that the reduction of aromatic hydrocarbons with
Sm(II) proceeds via an outer sphere mechanism,10a,14b,18,23,28o,p
the dramatic difference between the thermodynamic redox
potentials of SmI2 and SmI2(H2O)n determined by cyclic
voltammetry and the effective redox potentials as determined in
the current study suggests that these reductions may proceed
via inner sphere electron transfer. We believe that the
observation that SmI2(H2O)n is capable of reducing aromatic
hydrocarbons with redox potentials as low as −2.2 V vs SCE
will provide the framework for further mechanistic under-
standing of the electrostatic component31 that drives the
reductions mediated by Kagan’s reagent.
Scheme 6. Investigating the Protonation Step in the
Reduction of Aromatic Hydrocarbons with SmI2(H2O)n and
Related SET Reductants
cally powerful SmI2(D2O)n(Et3N) system gave 1,2-diphenyl-
ethane with >98% D2 incorporation; however, the use of
Na(silica) resulted in a significant loss of D2 incorporation
(Scheme 6A). Moreover, the reduction of 9,10-diphenylan-
thracene with SmI2(H2O)n, SmI2(H2O)n(Et3N) and Na(silica)
led to a gradual decrease in stereoselectivity of the protonation
(Scheme 6B). These results suggest that in the reductions with
Sm(II)-based reagents, anions are generated and immediately
protonated by H2O, whereas the SmI2(H2O)n reagent is less
sterically encumbered than SmI2(H2O)n(Et3N), resulting in a
highly diastereoselective protonation. Note that the intermedi-
ate monoanion in the reduction of trans-stilbene with
SmI2(D2O)n does not undergo stereoselective protonation.
To investigate the origin of selectivity in the reduction of 9-
anthracene carboxylic acid derivatives, we have carried out
intermolecular competition experiments using anthracene-
containing substrates and the corresponding benzoic acid
analogues with limiting SmI2(H2O)n (Scheme 7). The
reduction of aromatic carboxylic acids and esters with
SmI2(H2O)n systems has been previously reported.50 We
determined that the reduction of 9-anthracene carboxylic acid
and the methyl ester proceeds with complete selectivity over
the corresponding benzoic acid analogues. In addition, control
reactions using 17−20 (see Experimental Section) demon-
CONCLUSIONS
■
In summary, the first determination of the effective redox
potential of the versatile SmI2(H2O)n reagent has been carried
out. The reagent system has been found to reduce aromatic
hydrocarbons that have reduction potentials more positive than
−2.21 V vs SCE, which is much higher than the
thermodynamic redox potential of SmI2(H2O)n determined
by electrochemical methods (−1.3 V vs SCE). Determination
of the effective redox potential of the parent reductant
demonstrates that coordination of water to SmI2 increases
the effective reducing power of Sm(II) by more than 0.4 V.
Importantly, we have identified that in the reductions of
aromatic hydrocarbons the SmI2(H2O)n system in which n = 50
equiv of water is more reactive that the SmI2(H2O)n system
based on n = 500, which is in contrast to the thermodynamic
redox potential of SmI2(H2O)n complexes. Moreover, we have
described the synthesis and determination of the effective redox
potential of SmX2(H2O)n (X = Cl, Br) complexes for the first
time.
Scheme 7. Investigating the Origin of Selectivity in the Reduction of 9-Anthracene Carboxylic Acid Derivatives with
SmI2(H2O)n
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Scheme 8. Proposed Mechanism for the Reduction of Aromatic Hydrocarbons with SmI2(H2O)n Complexes
reported in hertz (Hz). Abbreviations are s, singlet; d, doublet; t,
triplet; q, quartet; br s, broad singlet.
The room temperature Birch reductions of substrates with at
least two aromatic rings mediated by SmI2(H2O)n constitute an
attractive practical alternative to the classic protocols employing
alkali metals in liquid ammonia. From a synthetic standpoint,
SmI2 is commercially available55 or convenient to prepare,35a
easy to handle,56 and the system based on SmI2(H2O)n does
not require any toxic cosolvents or additives,57 making this
transformation a valuable addition for the preparation of
dearomatized polycyclic hydrocarbons.
Experimental studies suggest that the observed selectivity in
the reduction of aromatic substrates originates from the initial
electron transfer step; however, some of the reductions
described herein might proceed through inner-sphere electron
transfer. As such, this study emphasizes the importance of
electrostatic interactions in processes mediated by lanthanide-
(II) reductants and aids in understanding the unique role of
SmI2(H2O)n complexes in the reduction of lactones and other
polar carbonyl groups. Further studies to investigate the role of
additives in Sm(II)-mediated reductions are ongoing in our
laboratory, and these results will be reported shortly. We
believe that the findings described herein will result in an
increased application of SmX2 and SmX2(H2O)n complexes in
organic synthesis.
Flash chromatography was performed on silica gel 60 Å, 230−400
mesh using commercial grade solvents. Samples were analyzed by thin-
layer chromatography analysis on aluminum sheets coated with silica
gel 60 Å F254, 0.2 mm thickness. The plates were visualized using a
254 nm ultraviolet lamp and/or aqueous potassium permanganate
solution.
All products and starting materials used in this study are
commercially available or have been previously reported. N,N-
Diethylanthracene-9-carboxamide and methyl anthracene-9-carboxy-
late were prepared according to the previously published proce-
dures.58,59 Their spectroscopic properties are reported below for
characterization purposes. All other products were identified using 1H
NMR, GC, and GC−MS analysis and comparison with authentic
1
samples. All yields were obtained by H NMR analysis using internal
standards added after workup unless stated otherwise.
GC−MS chromatography was performed using a GC system and
EI/CI MSD with triple axis detector equipped with a column (length
30 m, internal diameter 0.25 mm, film 0.25 μm) using helium as the
carrier gas at a flow rate of 1 mL/min and an initial oven temperature
of 40 or 50 °C. The injector temperature was 250 °C. The detector
temperature was 250 °C. For runs with the initial oven temperature of
40 °C, temperature was increased with a 15 °C/min ramp after 40 °C
hold for 3 min to a final temperature of 300 °C and then held at 300
°C for 5 min (splitless mode of injection, total run time of 25.33 min).
For runs with the initial oven temperature of 50 °C, temperature was
increased with a 25 °C/min ramp after 50 °C hold for 3 min to a final
temperature of 300 °C and then held at 300 °C for 5 min (splitlesss
mode of injection, total run time of 18 min).
GC chromatography was performed using a gas chromatograph
system equipped with a column (length 30 m, internal diameter 0.25
mm, film 0.25 μm) using hydrogen as the carrier gas at a flow rate of 1
mL/min and an initial oven temperature of 40 or 70 °C. The injector
temperature was 250 °C. The detector temperature was 250 °C. The
temperature was increased with a 10 °C/min ramp to a final
temperature of 150 or 220 °C (splitless mode of injection). For runs
with the initial oven temperature of 40 °C, temperature was increased
by 10 °C/min after 40 °C hold for 3 min (total run time of 13 min).
For runs with the initial oven temperature of 70 °C, temperature was
increased by 10 °C/min with no hold time (total run time of 15 min).
General Procedure A. Preparation of SmBr2. Lithium bromide
(7.65 g, 90 mmol, 12 equiv) was placed in a 500 mL Schlenk flask,
carefully flame-dried under vacuum, and allowed to cool to room
temperature. The flame-drying was repeated four more times. After the
final cycle, the flask was backfilled with argon, and freshly prepared
samarium(II) iodide solution (115 mL, 0.065 M in THF, 1 equiv) was
slowly added with vigorous stirring at room temperature. At this point
a change of color from deep blue indicative of samarium(II) iodide to
purple/violet indicative of the formation of samarium(II) bromide was
observed. After stirring for 15 min at room temperature the resulting
solution was used immediately.
EXPERIMENTAL SECTION
■
General Methods. All experiments were performed using standard
Schlenk techniques under argon atmosphere unless stated otherwise.
All solvents were purchased at the highest commercial grade and used
as received or after purification by passing through activated alumina
columns or distillation from sodium/benzophenone under nitrogen.
All solvents were deoxygenated by freeze−pump−thawing under
argon (three cycles) or sparging with argon prior to use. Samarium(II)
iodide was prepared as described previously.35a Samarium(II) bromide
and samarium(II) chloride were prepared according to the procedure
by Flowers and used immediately after the preparation.7 Samarium
metal was purchased as −40 mesh and stored in a closed container at
room temperature on the bench without further precautions prior to
use. 1,2-Diiodoethane was stored at 4 °C and used after purification as
described previously.35a Samarium(II) iodide powder was purchased,
opened and stored in an argon-containing glovebox (<1 ppm of O2,
H2O). All other chemicals were purchased at the highest commercial
grade and used as received. Reaction glassware was oven-dried at 140
°C for at least 24 h or flame-dried prior to use, allowed to cool under
vacuum, and purged with argon (three cycles).
1H NMR and 13C NMR spectra were recorded in CDCl3 on
spectrometers at 300, 400, and 500 MHz (1H NMR) and 75, 100, and
125 MHz (13C NMR). All shifts are reported in parts per million
1
(ppm) relative to the residual CHCl3 peak (7.27 and 77.2 ppm, H
NMR and 13C NMR, respectively). All coupling constants (J) are
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General Procedure B. Preparation of SmCl2. Lithium chloride
(4.00 g, 96 mmol, 12 equiv) was placed in a 500 mL Schlenk flask,
carefully flame-dried under vacuum, and allowed to cool to room
temperature. The flame-drying was repeated four more times. After the
final cycle, the flask was backfilled with argon, and freshly prepared
samarium(II) iodide solution (123 mL, 0.065 M in THF, 1 equiv) was
slowly added with vigorous stirring at room temperature. At this point
a change of color from deep blue indicative of samarium(II) iodide to
dark green indicative of the formation of samarium(II) chloride was
observed. After stirring for 15 min at room temperature the resulting
solution was used immediately.
General Procedure C. Preparation of SmX2(H2O)n (X = I, Br,
Cl) Complexes. An oven-dried vial or flask equipped with a Teflon-
coated magnetic stir bar and a septum was placed under a positive
pressure of argon. After three evacuation/backfilling cycles a freshly
prepared solution of samarium(II) halide (iodide, bromide, or
chloride) was added, followed by the addition of deoxygenated
deionized water (n = 50 or 500 equiv relative to SmX2). At this point a
change of color of SmX2 (X = I, Br, Cl) to burgundy red indicative of
the formation of SmX2(H2O)n complex was observed. The resulting
solution was used immediately.
General Procedure D. Determination of Stability of
SmX2(H2O)n Complexes. Method A. To an oven-dried vial equipped
with a Teflon-coated magnetic stir bar and a septum was added a
freshly prepared solution of SmX2 (X = I, Br, Cl) (1.0 mL, 0.065 M in
THF) followed by water (0.0586 mL, 50 equiv) with vigorous stirring
at room temperature. This resulted in an immediate color change to
burgundy red. The resulting solution of SmX2(H2O)n was stirred
under argon until decolorization to white had occurred. Note that
decolorization to yellow is indicative of a high concentration of O2
and/or Sm(III) salts. The time for decolorization (average of at least
three experiments) was found to be directly related to the redox
potential of the parent SmX2 reductant: SmI2(H2O)n more than 24 h,
SmBr2(H2O)n ca. 15−20 min, SmCl2(H2O)n ca. 5−7 min. Note that
the burgundy red color of SmBr2(H2O)n and SmCl2(H2O)n solutions
in THF is visibly darker than that of SmI2(H2O)n. Method B. To an
oven-dried vial equipped with a Teflon-coated magnetic stir bar and a
septum was added a freshly prepared solution of SmX2 (X = I, Br, Cl)
(1.0 mL, 0.065 M in THF) followed by the dropwise addition of water
with vigorous stirring at room temperature. For all three SmX2(H2O)n
complexes (X = I, Br, Cl) the characteristic burgundy red color
appeared after addition of ca. 0.050 mL (ca. 40 equiv) of H2O. Full
decolorization to white or transparent was observed after addition of
ca. 0.35−0.40 mL of H2O (SmBr2), 0.50 mL (SmCl2), and more than
12.5 mL (SmI2) for the three Sm(II) halides, respectively. Note that
SmCl2(H2O)n exhibits a limited solubility in THF solutions: a visible
precipitate forms after the addition of ca. 0.050 mL of water, which
then fully dissolves upon further addition of 0.25 mL of H2O,
indicating that H2O aids in solubilizing the SmCl2(H2O)n complex.
General Procedure E. Determination of Redox Potential of
SmX2(H2O)n (X = I, Br, Cl) by Reduction of Aromatic
Hydrocarbons or Alkyl Halides. To a preformed solution of
SmX2(H2O)n prepared as described above (THF solution, 3 equiv,
0.15 mmol) was added a solution of substrate (1 equiv, 0.05 mmol) in
THF (1.0 mL) at room temperature under argon atmosphere, and the
mixture was stirred vigorously. After the specified time, the reaction
was quenched by bubbling air through the reaction mixture until
decolorization had occurred. The sample was analyzed by GC and/or
1H NMR to obtain conversion using internal standard. For GC
typically 0.30 mmol) was added a solution of substrate (1 equiv,
typically 0.10 mmol) in THF (1.0 mL) at room temperature under
argon atmosphere, and the mixture was stirred vigorously. After the
specified time, the reaction was quenched by bubbling air through the
reaction mixture until decolorization had occurred. The reaction
mixture was diluted with CH2Cl2 (30 mL) and HCl (1 N, 30 mL).
The aqueous layer was extracted with CH2Cl2 (2 × 30 mL), and the
organic layers were combined, dried over MgSO4, filtered, and
concentrated. The sample was analyzed by 1H NMR to obtain
conversion and yield using an internal standard. Method B. An oven-
dried vial equipped with a Teflon-coated magnetic stir bar was charged
with a substrate (typically, 0.10 mmol) and placed under a positive
pressure of argon. Samarium(II) iodide (THF solution, typically 3
equiv), followed by H2O (typically, 50 equiv relative to SmI2), was
added, and the resulting mixture was stirred vigorously. Workup and
analysis was performed as described for Method A.
General Procedure G. Reduction of Aromatic Hydrocarbons
using SmI2(MeOH)n. To a freshly prepared solution of SmI2 (THF
solution, 3 equiv) was added MeOH (4:1 v/v, ca. 300 equiv), which
resulted in a color change from dark blue to dark brown indicative of
the formation of SmI2(MeOH)n complex. A solution of substrate (1
equiv, typically 0.10 mmol) in THF (1.0 mL) was added at room
temperature under argon atmosphere, and the mixture was stirred
vigorously. Workup and analysis were as described above for
reductions mediated by SmI2(H2O)n complexes.
General Procedure H. Determination of Deuterium Incor-
poration and Kinetic Isotope Effect. An oven-dried vial equipped
with a Teflon-coated magnetic stir bar was charged with a substrate
(0.10 mmol) and placed under a positive pressure of argon.
Samarium(II) iodide (THF solution, typically 3 equiv), followed by
D2O (typically, 50 equiv relative to SmI2; deuterium incorporation) or
an equimolar mixture of D2O and H2O (typically, 50 equiv relative to
SmI2; kinetic isotope effect), was added, and the resulting mixture was
stirred vigorously. After the workup as described above, the amount of
each species was determined by 1H NMR analysis (500 MHz, CDCl3).
General Procedure I. Determination of Chemoselectivity in
Reductions Mediated by SmI2(H2O)n. To a preformed solution of
SmI2(H2O)n prepared as described above (THF solution) was added a
solution of an equimolar mixture of substrates (each 0.10 mmol, 1.0
mL in THF) at room temperature under argon atmosphere, and the
mixture was stirred vigorously. After the specified time, the reaction
was quenched by bubbling air through the reaction mixture until
decolorization had occurred. After the workup as described above, the
1
sample was analyzed by GC−MS and H NMR to obtain product
distribution using internal standard.
General Procedure J. Reduction of Aromatic Hydrocarbons
using SmI2/Et3N/H2O Complexes. To a substrate (1 equiv, neat or
as a solution in THF) was added samarium(II) iodide (THF solution,
typically 3 equiv), followed by amine (typically, 24 equiv) and water
(typically, 24 equiv) under argon at room temperature, and the
resulting solution was stirred vigorously. Workup and analysis as
described above for reductions mediated by SmI2(H2O)n complexes.
General Procedure K. Reduction of Aromatic Hydrocarbons
using Na(silica). An oven-dried vial equipped with a Teflon-coated
magnetic stir bar was charged with Na(silica) (0.63 mmol, 2.5 equiv)
and placed under a positive pressure of argon. A solution of substrate
(0.25 mmol, 1 equiv) in THF (3.3 mL) was added, and the resulting
mixture was vigorously stirred for 5 h, followed by quenching with
H2O (3.0 mL) or D2O (3.0 mL). Workup and analysis as described
above for reductions mediated by SmI2(H2O)n complexes.
General Procedure L. Preparation of SmBr2 from 1,1,2,2-
Tetrabromoethane and its Reactivity with Aromatic Hydro-
carbons. An oven-dried vial equipped with a Teflon-coated magnetic
stir bar was charged with samarium metal (0.75 g, 5.0 mmol, 1.0
equiv), followed by THF (10 mL) and 1,1,2,2,-tetrabromoethane
(0.865 g, 2.5 mmol, 0.5 equiv) under a positive pressure of argon at
room temperature. After the reaction mixture was stirred for 3−6 h,
the color of the solution turned purple reminiscent of the color of
SmBr2 obtained from the reaction between SmI2 and LiBr. A solution
of substrate (0.30 g, 1.67 mmol, 0.33 equiv) in THF (5 mL) was
analysis, a small aliquot (typically, 0.25 mL) was removed from the
reaction mixture, diluted with diethyl ether (2.0 mL) and HCl (0.1 N,
0.25 mL), and analyzed by GC and/or GC−MS to obtain conversion.
1
For H NMR analysis, the reaction mixture was diluted with CH2Cl2
(30 mL) and HCl (1 N, 30 mL). The aqueous layer was extracted with
CH2Cl2 (2 × 30 mL), and the organic layers were combined, dried
over MgSO4, filtered, and concentrated. The product distribution was
analyzed after the addition of internal standard.
General Procedure F. Reduction of Aromatic Hydrocarbons
Using SmI2(H2O)n. Method A. To a preformed solution of
SmI2(H2O)n prepared as described above (THF solution, 3 equiv,
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added, and the resulting mixture was stirred for the indicated time.
Workup and analysis as described above for reductions mediated by
SmI2(H2O)n complexes.
73.5% D2 incorporation. Run B. 9,10-Diphenyl-9,10-dihydroanthra-
cene: yield 98%, trans:cis = 65:35.
Characterization Data. N,N-Diethylanthracene-9-carboxa-
mide. Prepared according to the reported procedure.58 Spectroscopic
properties were consistent with literature values. 1H NMR (300 MHz,
CDCl3) δ 0.85 (t, J = 7.2 Hz, 3 H), 1.52 (t, J = 7.2 Hz, 3 H), 3.02 (q, J
= 7.2 Hz, 2 H), 3.88 (q, J = 7.2 Hz, 2 H), 7.44−7.54 (m, 4 H), 7.91−
8.03 (m, 4 H), 8.44 (s, 1 H). 13C NMR (75 MHz, CDCl3) δ 13.2, 14.2,
39.2, 43.2, 125.0, 125.6, 126.6, 127.4, 127.6, 128.6, 131.3, 131.6, 169.6.
Methyl Anthracene-9-carboxylate. Prepared according to the
reported procedure.59 Spectroscopic properties were consistent with
literature values. 1H NMR (300 MHz, CDCl3) δ 4.11 (s, 3 H), 7.39−
7.51 (m, 4 H), 7.93−7.98 (m, 4 H), 8.47 (s, 1 H). 13C NMR (75 MHz,
CDCl3) δ 52.6, 125.0, 125.5, 127.0, 127.8, 128.5, 128.6, 129.5, 131.0,
170.1.
9,10-Dihydroanthracene (Table 11, entry 1). According to the
general procedure F for the reduction of aromatic hydrocarbons using
SmI2(H2O)n, anthracene (1 mmol) was reacted with samarium(II)
iodide (3 equiv) and water (50 equiv relative to SmI2) to give the title
product. Yield: 96% (172 mg) isolated after purification by column
chromatography (2% ethyl acetate/hexanes) and recrystallization from
ethanol. 1H NMR (500 MHz, CDCl3) δ 3.82 (s, 4 H), 7.07−7.11 (m,
4 H), 7.16−7.20 (m, 4 H). 13C NMR (125 MHz, CDCl3) δ 36.3,
126.2, 127.5, 136.8.
Additional Experimental Procedures for Reductions Medi-
ated by SmI2(H2O)n Complex. Competition Experiments on the
Origin of Selectivity in the Reduction of 9-Anthracenecarbox-
ylic Acid. According to the general procedure I, anthracene-9-
carboxylic acid or methyl anthracene-9-carboxylate (0.10 mmol) and
benzoic acid or methyl benzoate (0.10 mmol) were reacted with
samarium(II) iodide (1 equiv) and water (50 equiv relative to SmI2).
Decolorization to transparent occurred in the course of addition of
substrates to SmI2(H2O)n complex. After the workup as described
1
above, the sample was analyzed by GC−MS and H NMR to obtain
product distribution using an internal standard. Run A. Anthracene-9-
carboxylic acid:9,10-dihydroanthracene-9-carboxylic acid = 53:47,
combined yield = 99%; benzoic acid:benzyl alcohol >98:2, combined
yield >99%. Run B. Methyl anthracene-9-carboxylate:methyl 9,10-
dihydroanthracene-9-carboxylate = 57:43, combined yield = 96%;
methyl benzoate:benzyl alcohol >98:2, combined yield >99%.
Control Reactions to the Origin of Selectivity in the
Reduction of 9-Anthracenecarboxylic Acid. According to the
general procedure F for the reduction of aromatic hydrocarbons using
SmI2(H2O)n, (preformed complex), anthracene-9-carboxylic acid,
methyl anthracene-9-carboxylate, benzoic acid, and methyl benzoate
were reacted in separate vials with samarium(II) iodide (3 equiv) and
water (50 equiv relative to SmI2) for 30 s, followed by rapid quenching
with oxygen to yield yellow solutions. After the workup as described
above, the samples were analyzed by GC−MS and 1H NMR to obtain
product distribution using internal standard. Run A. 9,10-Dihydroan-
thracene-9-carboxylic acid: >95% conversion, 99% yield. Run B.
Methyl 9,10-dihydroanthracene-9-carboxylate: >95% conversion, 99%
yield. Run C. Benzoic acid: 69% conversion, 68% yield. Run D. Methyl
benzoate: 71% conversion, 66% yield.
9-Methyl-9,10-dihydroanthracene (Table 11, entry 2).
According to the general procedure F for the reduction of aromatic
hydrocarbons using SmI2(H2O)n, 9-methylanthracene was reacted
with samarium(II) iodide (3 equiv) and water (50 equiv relative to
1
SmI2) to give the title product. Yield: 99%. H NMR (400 MHz,
CDCl3) δ 1.34 (d, J = 7.5 Hz, 3 H), 3.81 (d, J = 18.4 Hz, 1 H), 3.97 (q,
J = 7.2 Hz, 1 H), 4.05 (d, J = 18.4 Hz, 1 H), 7.08−7.17 (m, 4 H),
7.19−7.24 (m, 4 H). 13C NMR (75 MHz, CDCl3) δ 23.5, 35.2, 41.1,
126.0, 126.4, 126.9, 127.7, 135.8, 141.8.
Relative Rates of the Reduction of E- and Z-Stilbene.
According to the general procedure I, trans-stilbene (0.10 mmol)
and cis-stilbene (0.10 mmol) were reacted with samarium(II) iodide (1
equiv) and water (50 equiv relative to SmI2) for 2 h. After the workup
trans-9,10-Diphenyl-9,10-dihydroanthracene (Table 11,
entry 3). According to the general procedure F for the reduction of
aromatic hydrocarbons using SmI2(H2O)n, 9,10-diphenylanthracene
was reacted with samarium(II) iodide (3 equiv) and water (50 equiv
relative to SmI2) to give the title product. Yield: 98%; dr > 98:2
1
as described above, the sample was analyzed by H NMR to obtain
1
1
determined by H NMR analysis of the crude reaction mixture. H
NMR (500 MHz, CDCl3) δ 5.24 (s, 2 H), 6.97−7.00 (m, 4 H), 7.04−
7.09 (m, 6 h), 7.11−7.14 (m, 4 H), 7.15−7.18 (m, 4 H). 13C NMR
(75 MHz, CDCl3) δ 50.0, 126.1, 126.5, 128.2, 129.2, 129.3, 138.5,
144.4. Dr was measured by comparison with an authentic sample of
cis-9,10-Diphenyl-9,10-dihydroanthracene obtained by the reduction of
9,10-diphenylanthracene with Na(silica) in THF (trans/cis = 65:35).
product distribution using internal standard. Relative reactivity values
were determined based on the recovered starting material. Run 1. cis-
Stilbene 91.7%, trans-stilbene 69.2%, bibenzyl 39.1%, kE/kZ = 3.71. Run
2. cis-Stilbene 91.8%, trans-stilbene 72.4%, bibenzyl 35.8%, kE/kZ
=
3.37. Average kE/kZ = 3.54.
Competition Experiments on the Chemoselectivity in Birch
Reductions of Aromatic Hydrocarbons. According to the general
procedure I, anthracene (0.10 mmol) and naphthalene, 1-chlorote-
tradecane, or bromobenzene (0.10 mmol) were reacted with
samarium(II) iodide (3 equiv) and water (50 equiv relative to SmI2)
for 1 h at room temperature. After the workup as described above, the
sample was analyzed by GC−MS to obtain yield and product
distribution using dodecane as internal standard.
Experiments with Other SET Reductants. A. SmI2−Et3N−H2O
System. According to the general procedure J, trans-stilbene (0.10
mmol) or 9,10-diphenylanthracene (0.05 mmol) were reacted with
samarium(II) iodide (3 equiv), triethylamine (24 equiv), and
deuterium oxide (24 equiv relative to substrate) or water (24 equiv
relative to substrate), respectively, for 1 h at room temperature. After
the workup as described above, the sample was analyzed by 1H NMR
to obtain product distribution and deuterium incorporation using
internal standard. Run A. 1,2-D2-1,2-Diphenylethane: yield 86%, >98%
D2 incorporation. Run B. 9,10-Diphenyl-9,10-dihydroanthracene: yield
82%, trans:cis = 79:21.
1
cis-9,10-Diphenyl-9,10-dihydroanthracene (diagnostic peaks only): H
NMR (500 MHz, CDCl3) δ 5.16 (s, 2 H), 7.02−7.08 (m, 12 H),
7.13−7.17 (m, 2 H), 7.20−7.24 (m, 2 H). 13C NMR (75 MHz,
CDCl3) δ 50.4, 126.5, 126.6, 128.5, 128.6, 129.4, 139.3, 143.8.
5,12-Dihydrotetracene (Table 11, entry 4). According to the
general procedure F for the reduction of aromatic hydrocarbons using
SmI2(H2O)n, tetracene was reacted with samarium(II) iodide (3
equiv) and water (50 equiv relative to SmI2) to give the title product.
1
1
Conversion: >98% determined by H NMR analysis. H NMR (400
MHz, CDCl3) δ 4.02 (s, 4 H), 7.12−7.16 (m, 2 H), 7.25−7.28 (m, 2
H), 7.32−7.37 (m, 2 H), 7.69 (s, 2 H), 7.69−7.74 (m, 2 H). 13C NMR
(125 MHz, CDCl3) δ 36.8, 125.2, 125.3, 126.3, 127.2, 127.3, 132.4,
135.7, 137.1.
1,2-Diphenylethane (Table 11, entry 5). According to the
general procedure F for the reduction of aromatic hydrocarbons using
SmI2(H2O)n, trans-stilbene was reacted with samarium(II) iodide (3
equiv) and water (100 equiv relative to SmI2) to give the title product.
Yield: 72% (two iterations). Note that the reaction using 3 equiv of
SmI2 and 50 equiv of water relative to SmI2 afforded the title product
in 62% yield. 1H NMR (300 MHz, CDCl3) δ 3.10 (s, 4 H), 7.31−7.40
(m, 6 H), 7.41−7.49 (m, 4 H). 13C NMR (75 MHz, CDCl3) δ 38.2,
126.1, 128.5, 128.6, 141.9.
B. Na(silica). According to the general procedure K, trans-stilbene
(0.25 mmol) or 9,10-diphenylanthracene (0.25 mmol) were reacted
with Na(silica) (2.5 equiv) in 3.3 mL of THF for 5 h at room
temperature. The reactions were quenched with 3.0 mL of deuterium
oxide (trans-stilbene) or water (9,10-diphenylanthracene). After the
1
workup as described above, the sample was analyzed by H NMR to
Ethane-1,1,2-triyltribenzene (Table 11, entry 6). According to
the general procedure J for the reduction of aromatic hydrocarbons
using SmI2(H2O)n, triphenylethylene was reacted with samarium(II)
obtain product distribution and deuterium incorporation using an
internal standard. Run A. 1,2-D2-1,2-Diphenylethane: yield: 93%,
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iodide (3 equiv), triethylamine (24 equiv), and water (24 equiv relative
to substrate) to give the title product. Yield: 97%. Note that the
reaction using SmI2 (3 equiv) and water (50 equiv relative to SmI2)
afforded the title product in 34% yield, consistent with the redox
potential of this substrate. 1H NMR (300 MHz, CDCl3) δ 3.28 (d, J =
7.8 Hz, 2 H), 4.16 (t, J = 7.8 Hz, 1 H), 6.90−6.95 (m, 2 H), 7.01−7.20
(m, 13 H). 13C NMR (75 MHz, CDCl3) δ 42.1, 53.1, 125.9, 126.2,
128.1, 128.4, 129.1, 140.3, 144.5.
ASSOCIATED CONTENT
■
S
* Supporting Information
1H and 13C NMR spectra for all new compounds. This material
is available free of charge via the Internet at http://pubs.acs.org.
AUTHOR INFORMATION
Corresponding Authors
*E-mail: michal.szostak@manchester.ac.uk
*E-mail: david.j.procter@manchester.ac.uk
Notes
■
9-Methyl-9,10-dihydroanthracene (Table 11, entry 7).
According to the general procedure F for the reduction of aromatic
hydrocarbons using SmI2(H2O)n, 9-(chloromethyl)anthracene was
reacted with samarium(II) iodide (5 equiv) and water (50 equiv
The authors declare no competing financial interest.
1
relative to SmI2) to give the title product. Yield: 74%. H NMR (400
MHz, CDCl3) δ 1.35 (d, J = 7.2 Hz, 3 H), 3.81 (d, J = 18.4 Hz, 1 H),
3.97 (q, J = 7.2 Hz, 1 H), 4.05 (d, J = 18.4 Hz, 1 H), 7.08−7.17 (m, J =
4 H), 7.19−7.24 (m, 4 H). 13C NMR (125 MHz, CDCl3) δ 23.5, 35.2,
41.1, 126.0, 126.4, 126.9, 127.7, 135.8, 141.8.
ACKNOWLEDGMENTS
■
We thank the EPRSC and GSK for support.
9,10-Dihydroanthracene-9-carboxylic Acid (Table 11, entry
8). According to the general procedure F for the reduction of aromatic
hydrocarbons using SmI2(H2O)n, anthracene-9-carboxylic acid was
reacted with samarium(II) iodide (3 equiv) and water (50 equiv
relative to SmI2) to give the title product. Yield: 94%. Note that the
reaction using large excess of SmI2 (10 equiv) and water (50 equiv
relative to SmI2) afforded the title product in quantitative yield. Over-
reduction was not observed. 1H NMR (300 MHz, CDCl3) δ 3.90 (d, J
= 18.3 Hz, 1 H), 4.28 (d, J = 18.3 Hz, 1 H), 4.96 (s, 1 H), 7.21−7.41
(m, 8 H). 13C NMR (75 MHz, CDCl3) δ 35.6, 52.5, 126.5, 127.7,
128.1, 128.4, 133.0, 136.6, 177.3.
Methyl 9,10-Dihydroanthracene-9-carboxylate (Table 11,
entry 9). According to the general procedure F for the reduction of
aromatic hydrocarbons using SmI2(H2O)n, methyl anthracene-9-
carboxylate was reacted with samarium(II) iodide (3 equiv) and
water (50 equiv relative to SmI2) to give the title product. Yield: 99%.
1H NMR (500 MHz, CDCl3) δ 3.52 (s, 3 H), 3.83 (d, J = 18.0 Hz, 1
H), 4.25 (d, J = 18.5 Hz, 1 H), 4.94 (s, 1 H), 7.15−7.22 (m, 4 H), 7.27
(d, J = 7.5 Hz, 2 H), 7.32 (dd, J = 1.5, 7.5 Hz, 2 H). 13C NMR (75
MHz, CDCl3) δ 35.7, 52.4, 52.9, 126.4, 127.5, 128.1, 128.3, 133.7,
136.7, 172.4.
N,N-Diethyl-9,10-dihydroanthracene-9-carboxamide (Table
11, entry 12). According to the general procedure F for the reduction
of aromatic hydrocarbons using SmI2(H2O)n, N,N-diethylanthracene-
9-carboxamide was reacted with samarium(II) iodide (3 equiv) and
water (50 equiv relative to SmI2) to give the title product. Yield: 98%.
1H NMR (500 MHz, CDCl3) δ 0.97 (t, J = 7.5 Hz, 3 H), 1.02 (t, J =
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1
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1
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