Mechanistic study of the SmI2/H2O/amine-mediated reduction of alkyl halides: Amine base strength (pKBH+) dependent rate

Article abstract of DOI:10.1021/ja043323u

The kinetics of the SmI₂/H₂O/amine-mediated reduction of 1-chlorodecane has been studied in detail. The rate of reaction is first order in amine and 1-chlorodecane, second order in SmI₂, and zero order in H₂O. Initial rate studies of more than 20 different amines show a correlation between the base strength (pK_BH+) of the amine and the logarithm of the observed initial rate, in agreement with Bronsted catalysis rate law. To obtain the activation parameters, the rate constant for the reduction was determined at different temperatures (0 to +40 °C, ΔH? = 32.4 ± 0.8 KJ mol^-1, ΔS? = -148 ± 1 J K^-1 mol^-1, and ΔG? _298K = 76.4 ± 1.2 kJ mol^-1). Additionally, the ¹³C kinetic isotope effects (KIE) were determined for the reduction of 1-iododecane and 1-bromodecane. Primary ¹³C KIEs (k ₁₂/k₁₃, 20 °C) of 1.037 ± 0.007 and 1.062 ± 0.015, respectively, were determined for these reductions. This shows that cleavage of the carbon-halide bond occurs in the rate-determining step. A mechanism of the SmI₂/H₂O/amine-mediated reduction of alkyl halides is proposed on the basis of these results.

Full text of DOI:10.1021/ja043323u

Published on Web 05/14/2005
Mechanistic Study of the SmI2/H2O/Amine-Mediated Reduction
of Alkyl Halides: Amine Base Strength (pKBH+) Dependent
Rate
Anders Dahle´n and Go¨ran Hilmersson*
Contribution from the Department of Chemistry, SE-412 96 Go¨teborg, Sweden
Received November 5, 2004; E-mail: hilmers@chem.gu.se
Abstract: The kinetics of the SmI2/H2O/amine-mediated reduction of 1-chlorodecane has been studied in
detail. The rate of reaction is first order in amine and 1-chlorodecane, second order in SmI2, and zero
order in H2O. Initial rate studies of more than 20 different amines show a correlation between the base
strength (pKBH+) of the amine and the logarithm of the observed initial rate, in agreement with Brønsted
catalysis rate law. To obtain the activation parameters, the rate constant for the reduction was determined
at different temperatures (0 to +40 °C, ∆Hq ) 32.4 ( 0.8 kJ mol-1, ∆Sq ) -148 ( 1 J K-1 mol-1, and
∆Gq298K ) 76.4 ( 1.2 kJ mol-1). Additionally, the 13C kinetic isotope effects (KIE) were determined for the
reduction of 1-iododecane and 1-bromodecane. Primary 13C KIEs (k12/k13, 20 °C) of 1.037 ( 0.007 and
1.062 ( 0.015, respectively, were determined for these reductions. This shows that cleavage of the carbon-
halide bond occurs in the rate-determining step. A mechanism of the SmI2/H2O/amine-mediated reduction
of alkyl halides is proposed on the basis of these results.
Introduction
ylphosphortriamide (HMPA), since the reduction potential of
SmI2/HMPA is considerably higher compared to that of SmI2.4
Reduction reactions represent a class of reactions that is
central in organic synthesis, where mainly three types of reagents
are used: hydride reagents, hydrogen, and dissolving metals.1
Today there are already a vast number of different reagents and
methods available for the reduction of, for example, alkyl halides
to hydrocarbons. However, the development of new more
efficient and selective methods, using environmentally friendly
reagents and possibly nonexplosive hydride/hydrogen-based
compounds, constitutes an important task for the organic
chemist. In this respect the single electron transfer reagent
SmI2 has received much interest since it has been found to
promote a number of selective reductions and reductive
couplings.2 Alkyl halides are readily and often with high
selectivity reduced into hydrocarbons by SmI2.3 However, SmI2
is not a very potent reducing reagent by itself; often it is used
in combination with the carcinogenic compound hexameth-
There are a few potential nontoxic substitutes to HMPA, but
none of these have received much attention.5
Recently, we discovered that addition of H2O and an aliphatic
amine to SmI2 in THF results in a very powerful reductant
(SmI2/H2O/amine). SmI2/H2O/amine is a much more powerful
reductant than the commonly used SmI2-HMPA mixture. The
rate enhancement in the reduction of ketones is more than
100 000 times that without the amine (or approximately 1000
times compared to SmI2-HMPA-MeOH), i.e., practically
instantaneous.6 During our continuing study we have observed
that the SmI2/H2O/amine mixture also reduces imines, R,â-
unsaturated esters, halides, and conjugated double and triple
bonds.7,8 Additionally, SmI2/H2O/amine readily cleaves allyl-
protected alcohols.9 The reagent mixture SmI2/H2O/amine is
particularly attractive not only because of its fast reductions
but also since it is a nonhazardous reducing agent.
(1) ComprehensiVe Organic Synthesis; Trost, B. M., Fleming, I., Eds.;
Pergamon Press: Oxford, 1991; Vol. 8. (b) Freifelder, M. Catalytic
Hydrogenation in Organic Synthesis: Procedures and Commentary; John
Wiley & Sons: New York, 1978. (c) Nylander, P. N. Hydrogenation
Methods; Academic Press: Orlando, FL, 1985. (d) Bunnett, J. F. Acc. Chem.
Res. 1992, 25, 2-9. (e) Yoon, N. M. Pure Appl. Chem. 1996, 68, 843-
848. (f) Alonso, F.; Beletskaya, I. P.; Yus, M. Chem. ReV. 2002, 102, 4009-
4091.
(2) Molander, G. A. Chem. ReV. 1992, 92, 29-68. (b) Molander, G. A. In
Organic Reactions, Vol. 46, Reductions with Samarium(II) Iodide; Paquette,
L. A., et al., Eds.; John Wiley & Sons: New York, 1994; pp 211-367. (c)
Molander, G. A.; Harris, C. R. Chem. ReV. 1996, 96, 307-338. (d) Krief,
A.; Laval, A.-M. Chem. ReV. 1999, 99, 745-777. (e) Molander, G. A.
Radicals in Organic Synthesis; Renaud, P., Sibi, M. P., Eds.; Wiley-VCH:
Weinheim, 2001; Vol. 1, pp 153-182. (f) Steel, P. G. J. Chem. Soc., Perkin
Trans. 1 2001, 21, 2727-2751. (g) Kagan, H. B. Tetrahedron 2003, 59,
10351-10372.
(3) Girard, P.; Namy, J. L.; Kagan, H. B. J. Am. Chem. Soc. 1980, 102, 2693-
2698. (b) Inanaga, J.; Ishikawa, M.; Yamaguchi, M. Chem. Lett. 1987,
1485-1486. (c) Kagan, H. B.; Namy, J. L.; Girard, P. Tetrahedron 1981,
37, 175-180.
To fully appreciate and develop new reactions using the
reagent mixture SmI2/H2O/amine, it is important that details
(4) Shabangi, M.; Flowers, R. A., II. Tetrahedron Lett. 1997, 38, 1137-1140.
(b) Shabangi, M.; Sealy, J. M.; Fuchs, J. R.; Flowers, R. A., II. Tetrahedron
Lett. 1998, 39, 4429-4432.
(5) Hasegawa, E.; Curran, D. P. J. Org. Chem. 1993, 58, 5008-5010. (b)
Kuhlman, M. L.; Flowers, R. A., II. Tetrahedron Lett. 2000, 41, 8049-
8052. (c) Cabri, W.; Candiani, I.; Colombo, M.; Franzoi, L.; Bedeschi, A.
Tetrahedron Lett. 1995, 36, 949-952.
(6) Dahle´n, A.; Hilmersson, G. Tetrahedron Lett. 2002, 43, 7197-7200.
(7) Dahle´n, A.; Hilmersson, G.; Knettle, B. W.; Flowers, R. A. J. Org. Chem.
2003, 68, 4870-4875.
(8) Dahle´n, A.; Hilmersson, G. Chem. Eur. J. 2003, 9, 1123-1128. (b) Dahle´n,
A.; Hilmersson, G. Tetrahedron Lett. 2003, 44, 2661-2664. (c) Kim, M.;
Dahle´n, A.; Hilmersson, G.; Knettle, B. W.; Flowers, R. A., II. Tetrahedron
2003, 59, 10397-10402.
(9) Dahle´n, A.; Sundgren, A.; Lahmann, M.; Oscarson, S.; Hilmersson, G. Org.
Lett. 2003, 5, 4085-4088.
9
8340
J. AM. CHEM. SOC. 2005, 127, 8340-8347
10.1021/ja043323u CCC: $30.25 © 2005 American Chemical Society

Alkyl Halide Reduction by SmI2/H2O/Amine
A R T I C L E S
and without H2O added was studied. Reaction rates were
measured by monitoring the formation of decane, in small
quenched portions of the reaction mixture, by GC. By individu-
ally varying the component concentrations over at least an 8-fold
range the reaction order in each component was obtained from
the slope of the plots of log(initial rate) vs log[component]. The
reaction order with respect to both SmI2 and halide was
determined to obtain the rate equation, eq 1. The rate of
reduction by SmI2 was found to be first order with respect to
both SmI2 and 1-chlorodecane. With H2O added a first-order
dependence was found for all three components, eq 2.
Figure 1. Reduction of alkyl halides by SmI2/H2O/amine.
regarding its mechanism of reduction are better understood. SmI2
is suggested to be a monomer in THF, and it crystallizes as a
pentagonal bipyramid, i.e., SmI2(THF)5.10 Furthermore, we and
other groups have previously shown that addition of water to a
THF solution of SmI2 results in a significant shift of the visible
band,7,11 indicating that one or several water molecules replace
THF ligands around samarium, i.e., SmI2(H2O)n(THF)5-n. The
amine appears to increase the oxidation potential of SmI2, but
no such effect has been established experimentally, suggesting
that the driving force for the reduction may be the precipitation
of the byproducts, Sm(OH)3 and R3NH+I-. However, the choice
of amine affects the rate of reduction, which indicates that the
amine must be intimately involved in the reduction mechanism.
The complete reduction of 1.0 mol of alkyl iodide requires
2.0 mol of SmI2, 5.0 mol of amine, and 6.0 mol of water. This
stoichiometry has been explained on the basis of the formation
of Sm(OH)3 and R3NHX salts that are observed to precipitate
out of the solution (Figure 1).7
rate ) Vinitial ) kobs[SmI2][1-chlorodecane]
(1)
rate ) Vinitial ) kobs[SmI2][1-chlorodecane][H2O] (2)
The reaction orders of the reduction of 1-chlorodecane were
then determined in the presence of SmI2/H2O/amine, Figure 2.
The respective reaction order for each component of the reaction
mixture is given in Table 1.
It is known that secondary halides are reduced faster than
primary halides. Additionally, it is clear that the leaving group
properties of the halides affect the rates of reduction, i.e., I >
Br > Cl. No primary kinetic isotope effect, i.e., kH O/kD O
)
2
2
1.0, was found for these reactions.7
Herein, we report the results on extensive kinetic studies of
the SmI2/H2O/amine-mediated reductions of simple alkyl halides
along with the dependence of the basicity of the amine versus
the rate of reduction. The temperature dependence of the rate
constant and the kinetic isotope effect for the reduction of
1-chlorodecane and 1-bromodecane have also been determined.
Based on the results of these studies a mechanism for the
SmI2/H2O/amine-mediated reduction reaction of alkyl halides
is suggested.
Figure 2. Plots of log(initial rate) vs (a) log[Et3N], (b) log[1-chlorodecane],
(c) log[SmI2], and (d) log[H2O].
Results
Table 1. Determined Reaction Orders with Respect to the
Respective Components of the SmI2/H2O/R3N-Mediated Reduction
of 1-Chlorodecane
Kinetics. The method of initial rates can be used for precise
and convenient determination of the reaction orders in a com-
plex system, as long as the reaction follows the same kinetics
throughout the course of the reaction.12 The first-order kinetics
in alkyl halide (R-X) was verified by following the SmI2/H2O/
amine-mediated reduction of different alkyl halides to at least
50% conversion and plotting ln([R-X]t/[R-X]0) versus time.
This yielded a straight line with the slope equal to -kobs
(Supporting Information).
component
reaction ordera
SmI2
H2O
1-chlorodecane
triethylamine
TMEDA
2.0 ( 0.1
0.1 ( 0.1
0.96 ( 0.04
0.98 ( 0.03
1.0 ( 0.1
PMDTA
pyrrolidine
0.95 ( 0.03 (at 1 equiv PMDTA)b
0.99 ( 0.1
1-Chlorodecane was chosen as substrate for the detailed
kinetic studies since it reacts at a rate that allows accurate
determination of the initial rate. First, the kinetics of the
background reduction of 1-chlorodecane by SmI2 in THF with
a The reported maximum errors are obtained from two separate experi-
ments. b The reaction order was 0.00 ( 0.03 when [PMDTA] < [SmI2].
The reaction orders in the reduction of 1-chlorodecane
with a mixture of SmI2, H2O, and an aliphatic amine (Et3N,
N,N,N′,N′-tetramethylethylenediamine (TMEDA), N,N,N′,N′′,N′′-
pentamethyldiethylenetriamine (PMDTA), or pyrrolidine) were
found to be first order in halide and amine, zero order in H2O,
and second order in SmI2, eq 3.
(10) Evans, W. J.; Gummersheimer, T. S.; Ziller, J. W. J. Am. Chem. Soc. 1995,
117, 8999-9002.
(11) Chopade, P. R.; Prasad, E.; Flowers, II, R. A. J. Am. Chem. Soc. 2004,
126, 44-45.
(12) Espenson, J. H. Chemical Kinetics and Reaction Mechanisms, 2nd ed.;
Speer, J. B., Morriss, J. M., Eds.; McGraw-Hill: New York, 1995; pp 8,
32. (b) Cox, B. G. Modern Liquid Phase Kinetics; Compton, R. G., Davies,
S. G., Evans, J., Eds.; Oxford University Press: New York, 1994; pp 12-
13. (c) Casado, J.; Lopez-Quintela, M. A.; Lorenzo-Barral, F. M. J. Chem.
Educ. 1986, 63, 450-452. (d) Hall, K. J.; Quickenden, T. I.; Watts, D. W.
J. Chem. Educ. 1976, 53, 493-494.
rate ) Vinitial ) kobs[SmI2]2[1-chlorodecane][amine] (3)
9
J. AM. CHEM. SOC. VOL. 127, NO. 23, 2005 8341

A R T I C L E S
Dahle´n and Hilmersson
a
Table 2. Determined Initial Rate (vinitial
)
of Reduction for the
b
Respective Amines with the Estimated pKBH+
1
entry
amine
vinitial
/
µ
M s-
pKBH
+
1
2
3
4
5
6
7
8
tribenzylamine
N-methylmorpholine
TMEDA
2-methoxyethylamine
morpholine
benzylamine
PMDTA
tributylamine
N-methylpyrrolidine
cyclohexylamine
triethylamine
isopropylamine
n-butylamine
0.05
0.09
0.70
1.17
1.22
2.51
4.12
0.45
1.99
20.9
2.87
17.3
26.2
26.7
25.9
6.9 ( 0.5
7.4 ( 0.1
8.6 ( 0.1
8.8 ( 0.1
9.0 ( 0.2
9.4 ( 0.1
9.6 ( 0.4
10.0 ( 0.5
10.6 ( 0.2
10.6 ( 0.1
10.6 ( 0.3
10.7 ( 0.3
10.7 ( 0.1
10.8 ( 0.1
10.8 ( 0.3
11.0 ( 0.3
11.0 ( 0.2
11.0 ( 0.2
11.1 ( 0.1
11.2 ( 0.2
11.3 ( 0.2
11.3 ( 0.4
11.4 ( 0.6
11.4 ( 0.2
14.4 ( 0.7
9
Figure 3. Eyring plot obtained by plotting ln(kobsh/kBT) vs 1/T.
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
Interestingly, the reaction order in PMDTA is zero at low
concentrations ([PMDTA] < [SmI2]). This is probably due to
the coordination of one PMDTA to one SmI2; however at higher
PMDTA concentrations the reaction is first order in PMDTA,
similarly to the other amines.
We also determined relative rates for reduction of the dif-
ferent alkyl halides (I, Br, Cl). The relative rates for the reduc-
tion of 1-iododecane, 1-bromodecane, and 1-chlorodecane
were approximately 1200:50:1. From the relative initial rates
diethylamine
diisopropylamine
N-ethyldiisopropylamine
n-dibutylamine
N-cyclohexylisopropylamine
quinuclidine
piperidine
pyrrolidine
2-methylpiperidine
2,6-dimethylpiperidine
dicyclohexylamine
hexamethyldisilazane
2.04
13.6
14.4
36.7
29.8
59.2
20.0
19.0
54.7
it was found that the activation energy (based on ∆Gq
)
-ln(krelh/kBT)) is approximately 7.9 kJ mol-1 higher for the
reduction of bromodecane and 18 kJ mol-1 higher for 1-chlo-
rodecane compared to that of 1-iododecane.
0.44
a [SmI2] ) 0.11 M, [Et3N] ) 0.11 M, [H2O] ) 0.33 M, and [1-chloro-
decane] ) 0.016 M. b The pKBH+ are obtained from ACD lab.15
It is known that the reduction of primary (1-chlorodecane),
secondary (s-BuCl), and tertiary (t-BuCl) alkyl chlorides varies
along the series according to kprim < ksec < ktert, indicating that
the number of alkyl substituents of the halide carbon has an
effect on the relative rate of reduction. In accordance with the
method by Rieke and co-workers, we determined the relative
rates of reduction of primary, secondary, and tertiary alkyl
chlorides.13 The rate of reduction of 1-chlorodecane rela-
tive to s-BuCl and t-BuCl was determined under pseudo-first-
order rate conditions (assuming similar rates of reduction of
n-BuCl and 1-chlorodecane). In these measurements 1 equiv
of SmI2, 3 equiv of H2O, 4 equiv of Et3N, 10 equiv of 1-chloro-
decane, and 10 equiv of s-BuCl or t-BuCl were used. The reac-
tion mixtures were analyzed with GC (with respect to 1-chlo-
rodecane) when all SmI2 had been consumed, i.e., when the
color of SmI2 had fully vanished. The relative rates, obtained
in these competition experiments, revealed that s-BuCl and
t-BuCl reacted 2 and 15 times faster, respectively, than
1-chlorodecane.
Temperature Dependence. The temperature dependence of
the reduction of 1-chlorodecane with SmI2/H2O/Et3N was
studied over the temperature interval from 0 to 40 °C with
increments of 5 °C. The measured initial rate is related to kobs
according to the obtained rate expression for the reaction (eq
3),14 with the assumption that the concentration of each
component is approximately equal to their initial concentration
(pseudo-first-order rate condition). An Eyring plot was obtained
by plotting ln(kobsh/kBT) vs 1/T (Figure 3).
of amine. The reductions appeared to be fastest with secondary
amines and slowest with tertiary amines, i.e., approximately
related to the basicity of the alkyl amines, tertiary < primary
< secondary. Initial rates of reduction were determined for a
large number of substituted alkyl amines at 20 °C (Table 2).
The basicity corresponds to the pKBH+ values of the amines in
water (estimated with the ACD software).15,16
The use of less basic aryl amines, e.g., substituted pyridines,
together with SmI2 and H2O in the reduction of 1-chlorodecane
failed. The characteristic blue color of SmI2 in THF disappeared
immediately, indicating that Sm2+ was oxidized to Sm3+. No
trace of the reduced alkyl halide could be detected after workup.
This indicates that these less basic aryl amines are reduced to
piperidines in the reaction mixture, which Kamochi and Kudo
have reported previously.17
Addition of the very basic amine hexamethyldisilazane,
HMDS (pKBH+ ) 14.4), to SmI2/H2O did not increase the
rate of reduction. in fact this rate was slightly lowered com-
pared to the rate of SmI2/H2O alone. The reaction orders were
also determined for each of the components of the mixture
SmI2/H2O/HMDS. The expression for the initial rate was
identical to that of the SmI2 in THF-mediated reduction (eq 1)
when [HMDS] > [H2O]. The lack of rate enhancement using
(13) Gujarro, A.; Rosenberg, D. M.; Rieke, R. D. J. Am. Chem. Soc. 1999, 121,
4155-4167.
(14) kobs is obtained by dividing the initial rate with [SmI2]2[R-X][amine].
(15) ACD Lab, ACD/pKa, DB 1996-2004, Advanced Chemistry Development.
The pKa predictions are based on 16 000 compounds and 30 000 experi-
mental pKa values. Additionally, the pKa prediction algorithm applies a
linear free energy relationship (Hammett equation) and sigma constants to
describe the level of electron donation and withdrawal at the ionization
center. Correction for organic solvent can also be applied.
Activation parameters for the reduction reaction were obtained
from the linear correlation according to the Eyring equation
(ln(kobsh/kBT) ) -∆Hq/RT + ∆Sq/R), i.e., ∆Hq ) 32.4 ( 0.8
(16) Graton, J.; Laurence, C.; Berthelot, M.; Le Questel, J.-Y.; Besseau, F.;
Raczynska, E. D. J. Chem. Soc., Perkin Trans. 2 1999, 997-1001. (b)
Graton, J.; Berthelot, M.; Laurence, C. J. Chem. Soc., Perkin Trans. 2 2001,
2130-2135. (c) Barbosa, J.; Berge´s, R.; Sanz-Nebot, V. J. Chromatogr.,
A 1998, 823, 411-422.
(17) Kamochi, Y.; Kudo, T. Yakugaku Zasshi 2000, 120, 245-255. (b) Kamochi,
Y.; Kudo, T. Kidorui 1993, 22, 56-57. (c) Kamochi, Y.; Kudo, T.
Heterocycles 1993, 36, 2383-2396.
kJ mol-1, ∆Sq ) -148 ( 1 J K-1 mol-1, and ∆Gq ) 76.4
298
( 1.2 kJ mol-1. The corresponding Gibbs free energy of
activation was calculated from ∆Gq ) ∆Hq - T∆Sq at 298 K.
Amine Basicity. During the kinetic studies it was observed
that the rate of reduction was strongly dependent on the choice
9
8342 J. AM. CHEM. SOC. VOL. 127, NO. 23, 2005

Alkyl Halide Reduction by SmI2/H2O/Amine
A R T I C L E S
the strong base HMDS could indicate that it is too basic to be
used together with water.
act as nucleophiles since the nucleophilicity of amines generally
correlates well with their basicity. To exclude the possibility
that the reaction does not involve nucleophilic catalysis, triethyl
phosphine (Et3P), which is a known powerful nucleophile and
a weak base, was utilized. Interestingly, the rate of reduction
using SmI2/H2O/Et3P was lower than that with only SmI2/H2O,
and the rate of reduction decreased with increasing amounts of
Et3P.
It is also possible that the free iodide (I-) could act as a
catalyst for the reduction reactions. Iodide is a known good
nucleophile; therefore the kinetics of the SmI2/H2O/amine-
mediated reduction of 1-chlorodecane was also studied in the
presence of excess LiI (3:1 molar ratio of LiI:SmI2). How-
ever, no measurable difference in initial rates was observed.
Catalytic amounts of HgI2 and NiI2 are other additions that
previously have been reported to accelerate some SmI2-mediated
reactions,18 but neither HgI2 nor NiI2 could be used in the
SmI2/H2O/amine-mediated reduction of alkyl halides. They were
instantaneously reduced to Hg(0) and Ni(0), in agreement with
their low reduction potentials.
A surprisingly good correlation was obtained in the Brønsted
plot constructed by plotting the initial rates of reduction vs the
pKBH+ of the corresponding protonated amines, BH+ (Figure
4). Only the hindered, tertiary amines, such as Bu3N and
Et(i-Pr)2N, are slightly outside the linear correlation, possibly
due to some steric effects. From the slope of the plot of
log(Vinitial) vs pKBH+ a Brønsted value of 0.60 was estimated
(Figure 4b). Exclusion of the values for tertiary amines certainly
gives a better correlation; however the Brønsted â is only
affected slightly (∼0.64), concluding that a higher pKBH+ of
the amines give higher rates of reduction.
Additions of NaOH, NH4Cl, or LiCl. To probe if the
reduction of 1-chlorodecane is faster at higher pH, the reduction
was carried out after addition of saturated aqueous NaOH (50%)
with a 1:2 molar ratio of NaOH-SmI2. Interestingly, the
reduction of the alkyl halide by SmI2/NaOH/H2O proceeded with
an initial rate approximately 15 times as high as that using
SmI2/H2O alone. However, the large rate enhancements were
only observed for a few percent of the reaction, and at about
5% conversion the reaction had almost stopped, possibly due
to breakdown of SmI2.
Addition of 3 equiv of NH4Cl to a mixture of H2O and SmI2
resulted in a small increase in the rate of reduction of
1-chlorodecane. The rate of the SmI2/NH4Cl/H2O-mediated
reduction was determined to be 2.5 times faster than that by
SmI2/H2O. Furthermore, a small enhanced rate of reduction upon
addition of LiCl to SmI2/H2O was also observed. This small
but significant increase in rate is in agreement with an
observation, reported by Flowers et al., that LiCl increases the
reduction potential and the reactivity of SmI2.19
Figure 4. (a) Plot of initial rate (Vinitial) vs pKBH+ and (b) log(Vinitial) vs
pKBH+ of the protonated amines. The result for HMDS has been excluded
in the linear plot, as it is protonated by water.
UV Studies. Water is known to coordinate to SmI2 in THF,
giving rise to a characteristic UV band indicating that H2O
replaces THF in the coordination sphere of SmI2, Figure 5.
Careful inspection of the UV bands shows that there are three
isosbestic points present, at 407, 474, and 521 nm, respectively.
Addition of the strong amine HMDS to a solution of SmI2
and H2O results in a UV spectrum identical to that of pure SmI2
in THF. This indicates that neither HMDS nor water is
coordinated to SmI2. HMDS most likely deprotonates water,
resulting in an ion-pair (HMDSH+OH-), which precipitate out
of the THF solution. Addition of any of the other amines in
Table 2 to a mixture of SmI2/H2O in THF did not affect the
UV spectra.
Kinetic Isotope Effects. Kinetic isotope effects (KIEs) are
useful in mechanistic studies, as they can give information about
rehybridization changes occurring in the transition state. The
size of a primary heavy 13C KIE in the SmI2/H2O/Et3N-mediated
reduction of alkyl halides could also indicate that the rate-
determining step involves the breakage of the carbon-halogen
bond. Likewise there should also be a secondary kinetic isotope
effect if there is a rehybridization of the CH2 bonded to the
halide. Accurate 13C or 2H KIE can be obtained from the change
in isotopic composition (13C/12C) of reactions taken to 85-95%
conversion using a simple method extensively used by, for
example, Singleton.20 The analysis requires only 13C or 2H NMR
integrals of reference materials and unreacted reactants. The KIE
is calculated from eqs 4 and 5 below, where the term (R/R0) is
Comparison of Nucleophilicity. The dependence of the
initial rate with choice of amine can also indicate that the amines
(18) Machrouhi, F.; Hamann, B.; Namy, J. L.; Kagan, H. B. Synlett 1996, 7,
633-634.
(19) Fuchs, J. R.; Mitchell, M. L.; Shabangi, M.; Flowers, R. A., II. Tetrahedron
Lett. 1997, 38, 8157-8158.
(20) Martin, G. J.; Martin, M. L. Tetrahedron Lett. 1981, 22, 3525-3528. (b)
Zhang, B. Magn. Reson. Chem. 1988, 26, 955-959. (c) Singleton, D. A.;
Thomas, A. A. J. Am. Chem. Soc. 1995, 117, 9357-9358. (d) Singleton,
D. A.; Nowlan, D. T., III; Jahed, N.; Matyjaszewski, K. Macromolecules
2003, 36, 8609-8616.
Figure 5. UV spectra of SmI2 in THF with increasing amounts of H2O
added.
9
J. AM. CHEM. SOC. VOL. 127, NO. 23, 2005 8343

A R T I C L E S
Dahle´n and Hilmersson
Scheme 1
bestic points in the UV-vis spectra indicate that H2O replaces
one or several THF molecules in SmI2(THF)5, e.g., SmI2(H2O)n-
(THF)5-n, to form one new complex (Scheme 1). Previously
we have reported on the absence of an observable change of
the UV-vis spectra for the SmI2-THF solution upon addition
of aliphatic monodentate amines (having pKBH+ < 13); that is,
it does not coordinate to the SmI2 complex in the initial state.7
Addition of the tridentate amine N,N,N′,N′′,N′′-pentameth-
yldiethylene triamine (PMDTA) results in a shift of the
UV-vis, yielding several isosbestic points. Thus, the tridentate
amine PMDTA competes effectively with THF in coordination
to SmI2. On the basis of the isosbestic points in the UV-vis
spectrum, it is suggested that there is only one PMDTA
coordinated to SmI2 in the initial state.22 This also establishes
that the amine is not strong enough to deprotonate SmI2(H2O)n-
(THF)5 to any significant extent, as judged from the UV-vis
spectra, although we cannot exclude a possible dimerization of
SmI2 induced by H2O.
Figure 6. 13C KIEs were obtained from the isotopic ratios (12C/13C) and
H/D for the C1-methylene group of 1-iododecane and 1-bromodecane in
the reduction by SmI2/H2O/Et3N in THF. The isotopic ratio of the C2-
methylene group is used as internal reference (assumed 1.000).
Table 3. Observed KIEs for the Reduction of 1-Iododecane and
1-Bromodecane Mediated by SmI2/H2O/Et3N in THF
alkyl halide
conversion
(%)
isotopic
ratio
KIE
1-iododecane
1-bromodecane
96
85
1.134
1.117
1.086
1.037 ( 0.007 (k12/k13)
1.062 ( 0.015 (k12/k13)
1.041 ( 0.020 (kH/kD)
the proportion of minor isotopic component in recovered
material compared to the original starting material and the
variable (F) is the fractional conversion of reactant.
R/R0 ) (1 - F)(1/KIE)-1
(4)
Recently Flowers and co-workers reported that water coor-
dinates much stronger to SmI2 than alcohols.11 In addition they
found that water gives the highest rate enhancement in the
reduction of acetophenone, indicating that water may be unique
among proton donors to promote dimerization. However, the
rate of reduction is zero order in water and first order in amine,
regardless of the amine used (Et3N, TMEDA, PMDTA, or
pyrrolidine), despite the fact that these amines differ largely in
both structure and basicity. This indicates similar reaction
mechanisms. The kinetic zero order with respect to water
suggests that it binds tightly to SmI2 in THF. Assuming that
SmI2 is a monomer in the initial state, then a second-order
dependence on SmI2 shows that the transition state is a dimer
or that the reaction proceeds in two steps with the second being
rate determining. The background reductions of the alkyl halide
(by SmI2 or SmI2/H2O) proceed via significantly different
mechanisms than SmI2/H2O/amine. The reduction reaction using
SmI2/H2O is first order in SmI2, H2O, and alkyl halide.
Electron Transfer from SmI2 to the Alkyl Halide. Water
is crucial for the fast reaction by SmI2/H2O/amine but does not
appear in the rate expression because it is coordinated to SmI2
in the initial state. The amine is not coordinated to SmI2 in the
initial state, but it could be part of a rapid and unfavorable acid-
base pre-equilibrium leading to a short-lived dimeric high-energy
intermediate. Moreover, the reduction of 1-chlorodecane by
SmI2/H2O/amine proceeds with a small enthalpy and large
negative entropy of activation. The negative entropy of activa-
tion indicates that there are more molecules bound in the
transition state than in the initial state. The enthalpy of activation
of 32.4 kJ mol-1 is almost identical to the value of 33 kJ mol-1
reported by Flowers et al. for the reduction of 1-iodobutane by
a SmI2-HMPA mixture.23 However, the entropy of activation
ln(1 - F)
ln[(1 - F)R/R0]
KIEcalcd
)
(5)
Since 1-chlorodecane is slowly reduced with SmI2/H2O/Et3N
and quantitative yields are difficult to obtain, 1-iododecane and
1-bromodecane were instead employed in these heavy atom KIE
studies. The relative change of the 13C integral of the C1-carbon
vs the C2-carbon (used as internal standard) corresponds to the
relative change in the isotopic composition of 13C at the C1
carbon, Figure 6. The C2 carbon integral was used as internal
standard since it does not participate in the reaction; hence its
isotopic composition is unaffected by the reaction conditions.
The primary 13C KIE (k12/k13) for the cleavage of the carbon-
iodide bond was found to be 1.037 ( 0.007 at 20 °C.
1-Bromodecane was treated with SmI2/H2O/Et3N, and the
reaction was taken to 85% conversion. The 13C kinetic isotope
effect for the C1 carbon was calculated from the fractional
conversion and the measured changes in isotopic composition.
The primary 13C KIE (k12/k13) for the cleavage of the carbon-
bromide bond was 1.062 ( 0.015 at 20 °C. Natural abundance
2H NMR was employed to obtain the 1H/2H isotopic composition
of the remaining 1-bromodecane compared to a reference sample
of unreacted 1-bromodecane. The secondary kH/kD KIE was
determined to be 1.041 ( 0.020. In these KIE studies no
compensation for contributions from isotope effects imposed
by the halide was made, simply because the effects would be
too small to be observed by the method used.21
Discussion
Dimerization of SmI2 by Amine and Water. SmI2 exists
as a pentagonal bipyramid, SmI2(THF)5, in THF.10 The isos-
(21) Values of approximately 1.003 and 1.010 have been reported in the literature
for 79Br/81Br and 35Cl/37Cl KIE, respectively. (a) Dybaa-Defratyka, A.;
Rostkowski, M.; Matsson, M.; Westaway, K. C.; Paneth, P. J. Org. Chem.
2004, 69, 4900-4905. (b) Lewandowicz, A.; Sicinska, D.; Rudzinski, J.;
Ichiyama, S.; Kurihara, T.; Esaki, N.; Paneth, P. J. Am. Chem. Soc. 2001,
123, 9192-9193.
K
(22) The equilibrium constant of SmI2 + PMDTA y
\
z SmI2(PMDTA) was
determined from the UV spectra, K ) 33 M-1, see ref 7.
9
8344 J. AM. CHEM. SOC. VOL. 127, NO. 23, 2005

Alkyl Halide Reduction by SmI2/H2O/Amine
A R T I C L E S
Scheme 2
The heavy atom KIE is slightly larger with 1-bromodecane than
with 1-iododecane, as expected from their differences in mass.27
The electron transfer (ET) from complex B to the alkyl halide
may proceed via an inner or an outer sphere mechanism. The
k12/k13 KIE does not differ significantly for an inner and an outer
sphere electron transfer mechanism.28 On the other hand the
secondary-deuterium KIEs have been suggested to differ
considerably for electron transfer mechanisms proceeding via
outer sphere (kH/kD ≈ 1.01-1.04) and inner sphere electron
transfer (kH/kD ≈ 1.30-1.50). The observed small secondary
kH/kD KIE of 1.041 ( 0.020 therefore suggests that the reduction
of 1-bromodecane proceeds via an outer sphere electron transfer
mechanism. However, the validity of this distinction has been
questioned since some electron transfers may be diffusion
controlled.29 There are also different opinions whether the SmI2/
HMPA-mediated reduction of alkyl halides proceeds through
an inner or an outer sphere electron transfer.23,30 Still, the clean
reaction orders strongly indicate a system with an unstable
intermediate. Therefore the rate of electron transfer is much
lower than that of dissociation of the SmI2 precomplex B, i.e.,
kET , kdiss (Schemes 2 and 3). The Marcus theory describes
outer sphere electron transfer reactions.31 According to this
theory outer sphere ET generally shows a correlation between
∆Gq and ∆G° for the reaction. The ∆Gq’s for the reduction of
the decyl halides were obtained from the respective initial rates,
and the ∆G°’s for the alkyl halides were taken from the
potentials of butyl chloride (E ) 1.246 V), butyl bromide (E )
1.105 V), and butyl iodide (E ) 1.075 V) reported by Save´ant
and co-workers (assuming similar relative potentials for decyl
and butyl).32 The experiments show that decyl bromide and
decyl chloride have 7.9 and 18 kJ mol-1, respectively, higher
activation energy than decyl iodide, while the reported free
energies are 3.3 and 18 kJ mol-1, respectively, higher than decyl
iodide. Thus, there is indeed a good correlation between ∆Gq
(decyl halides) and ∆G° (butyl halides) with the slope being
almost unity, consistent with an outer sphere electron transfer.
The outer sphere electron transfer to alkyl halides has received
much attention; both Save´ant and Fukuzumi with co-workers
have reported that the rate of reduction is insensitive to steric
hindrance.32,33 Furthermore, Rieke and co-workers reported that
there is only a limited difference in rate of reductions of isomeric
alkyl halides for outer sphere electron transfer reactions.13 An
Scheme 3. Mechanism Describing the Final Steps in the
Reduction of Alkyl Halides (solvent molecules have been excluded
for clarity)
of -148 J K-1 mol-1 for SmI2/H2O/amine is significantly more
negative than the value of -125 J K-1 mol-1 for SmI2-HMPA.
This substantial loss in entropy indicates that the reaction
proceeds through a larger molecular assembly, possibly a dimer
(Scheme 2).
Altogether, the results of the kinetic measurements indicate
that the amine is involved in an unfavorable, fast deprotonation
of a coordinated water molecule in complex A. The absence of
changes in the UV-vis spectra with the addition of an amine
to complex A indicates a necessary, but also unfavorable, pre-
equilibrium deprotonation that transforms into the short-lived
anion intermediate B.
Complex B, being negatively charged, can be the powerful
reductant responsible for the fast reductions with SmI2/H2O/
amine. Thus, the activated complex for the SmI2/H2O/amine-
mediated reduction of 1-chlorodecane is suggested to consist
of a dimer of SmI2 with one bridging water molecule, one
hydroxide, and possibly two more coordinated water molecules,
the protonated amine, and the alkyl halide, Scheme 3. It is
possible that dimers of SmI2 with bridging water molecules may
also exist in the absence of amine.24 Corresponding bridging
oxygens bound to two samariums have previously been observed
for SmIII in the solid state.25 The occurrence of dimeric samarium
species has also been proposed by Curran et al. to explain the
mechanistic behavior of intramolecular samarium Barbier
couplings.26
alkyl halide that undergoes outer sphere ET has ln(ks-R-X
/
(27) Melander, L.; Saunders, W. H., Jr. Reaction Rates of Isotopic Molecules;
John Wiley & Sons: New York, 1980; pp 8-24.
(28) Holm and Crossland have reported a k12/k13 ) 1.035 for inner sphere
electron transfer to CH3I to generate methyl radicals at 250 °C. They
estimated that the k12/k13 would correspond to 1.056 at 20 °C. They also
reported that an outer sphere electron transfer mechanism may give rise to
a k12/k13 KIE of 1.023 ( 0.009. Holm T.; Crossland I. Acta Chem. Scand.
1996, 50, 90-93.
Inner vs Outer Sphere Electron Transfer. The observed
13C kinetic isotope effects (k12/k13) of 1.037 ( 0.007 and 1.062
( 0.015 for 1-iododecane and 1-bromodecane, respectively,
indicate partial carbon-halide bond breakage in the rate-
determining step, in agreement with the proposed mechanism.
(29) Holm, T. J. Am. Chem. Soc. 1999, 121, 515-518.
(30) Enemarke, R. J.; Daasbjerg, K.; Skrydstrup, T. Chem. Commun. 1999, 4,
343-344. (b) Enemarke, R. J.; Hertz, T.; Skrydstrup, T.; Daasbjerg, K.
Chem. Eur. J. 2000, 6, 3747-3754. (c) Shabangi, M.; Kuhlman, M. L.;
Flowers, R. A., II. Org. Lett. 1999, 1, 2133-2135. (d) Miller, R. S.; Sealy,
J. M.; Shabangi, M.; Kuhlman, M. L.; Fuchs, J. R.; Flowers, R. A., II. J.
Am. Chem. Soc. 2000, 122, 7718-7722.
(31) Albery, W. J. Ann. ReV. Phys. Chem. 1980, 31, 227-263. (b) Jordan, R.
B. In Topics in Inorganic Chemistry: Reaction Mechanisms of Inorganic
and Organometallic Systems; Oxford University Press: New York, 1998;
pp 188-220.
(32) Save´ant, J.-M. J. Am. Chem. Soc. 1987, 109, 6788-6795.
(33) Fukuzumi, S.; Suenobu, T.; Hirasaka, T.; Arakawa, R.; Kadish, K. M. J.
Am. Chem. Soc. 1998, 120, 9220-9227. (b) Ishikawa, M.; Fukuzumi, S.
J. Am. Chem. Soc. 1990, 112, 8864-8872. (c) Andrieux, C. P.; Gallardo,
I.; Save´ant, J.-M. J. Am. Chem. Soc. 1989, 111, 1620-1626. (d) Andrieux,
C. P.; Gallardo, I.; Save´ant, J.-M. J. Phys. Chem. 1986, 90, 3815-3823.
(23) Prasad, E.; Flowers, R. A., II. J. Am. Chem. Soc. 2002, 124, 6895-6899.
(24) Flowers, R. A., II. Lehigh University, PA, unpublished results.
(25) Massarweh, G.; Fischer, R. D. J. Organomet. Chem. 1993, 444, 67-74.
(b) Stehr, J.; Fischer, R. D. J. Organomet. Chem. 1993, 459, 79-86. (c)
Hou, Z.; Fujita, A.; Yamazaki, H.; Wakatsuki, Y. J. Am. Chem. Soc. 1996,
118, 7843-7844. (d) Ma, W.-W.; Wu, Z.-Z.; Cai, R.-F.; Huang, Z.-E.; Sun,
J. Polyhedron 1997, 16, 3723-3728.
(26) Curran, D. P.; Gu, X.; Zhang, W.; Dowd, P. Tetrahedron 1997, 53, 9023-
9042.
9
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A R T I C L E S
Dahle´n and Hilmersson
kn-R-X) of less than unity and ln(kt-R-X/kn-R-X) less than 3,
respectively. By taking the logarithm of the relative rate ratios,
coupling reactions. We have observed reductive coupling
reactions only between aromatic ketones and imines and the
intramolecular aryl halide olefin coupling.8a,c,37 This is probably
due to the fact that these generated radicals are relatively stable
and long-lived.
it was found that ln(ks-BuCl/k1-chlorodecane) ) 0.6 and ln(kt-BuCl
1-chlorodecane) ) 2.7, indicating that the reduction by SmI2/H2O/
amine mainly proceeds through an outer sphere process.
/
k
Fast electron transfer to the radical from the remaining SmII
in the mixed SmII/SmIII dimer complex is suggested to result in
an organosamarium(III) complex, which rapidly decomposes
in the presence of H2O and the amine. Such organosamarium
intermediates are assumed to be central in the SmI2-mediated
reduction of alkyl halides.38 Breakdown of the organosamarium
intermediate into R-H must proceed after the rate-limiting step.
Once the stable byproducts Sm(OH)3 and R3NH+X- are formed,
they precipitate from the solution.
Amine Base Strength Dependent Rate. The observed
Brønsted â of 0.6 may indicate significant proton transfer in
the activated complex; however in the absence of an observable
KIE (kH O/kD O ) 1.0) the proton transfer cannot be involved
2
2
in the rate-determining step.7 The role of the amine may thus
be to deprotonate a water molecule coordinated to SmI2 in a
pre-equilibrium. The proton transfer is therefore suggested to
occur in such a fast pre-equilibrium leading to a high-energy
intermediate, occurring prior to the actual electron transfer step.
In such a model there should be only an equilibrium isotope
effect, which would be close to unity.34 The observed Brønsted
â thus indicates that a stronger base is able to push the
equilibrium toward the high-energy intermediate, with a faster
overall rate of reduction. Water molecules coordinated to a
Lewis acid, i.e., samarium diiodide, should show an enhanced
acidity; that is, the pKa of Lewis acid coordinated water
molecules is approximately 9.35
The above mechanism suggests that the use of NaOH/H2O
instead of amine/H2O would lead to a similar mechanism.
However, the initially fast reduction (ca. 15 times faster) using
SmI2/NaOH/H2O is observed only for a fraction of the reaction,
after which the rate of reduction is slow and similar to that of
SmI2/H2O. This is probably due to rapid breakdown of SmI2 in
this harsh environment and because the driving force from
precipitated ammonium salts is lost when no amine is present.
Addition of other salts (NaI, LiI, NaCl, or NH4Cl) has no
significant effect on the rate of reduction, although the sodium
and lithium salts have limited solubility in THF. The addition
of excess NH4Cl (3 equiv) results in a 2.5 times increase in the
rate of reduction by SmI2/H2O. This small, but significant,
increase in rate is in agreement with Flowers finding that LiCl
increases the reduction potential and the reactivity of SmI2.19
This effect is similar to that observed by the addition of LiBr.
The use of Brønsted â values in mechanistic studies is
somewhat controversial, and there are different interpretations
of what a certain value indicates.36 The Brønsted â value may
reflect the charge formed in the transition state rather than the
extent of bond formation. It should also be emphasized that
these reductions proceed in mixtures of THF-H2O (37:1) and
not in pure H2O, for which the Brønsted catalysis law is defined.
The â value can also be a measure of the nucleophilicity of the
amine, suggesting that an amine coordinated to SmI2 could result
in a more powerful reductant. However, previous cyclic volta-
mmetric (CV) studies on the SmI2(PMDTA) complex have
shown that this complex is not a stronger reducing agent than
SmI2(THF)5, and the use of the powerful nucleophile Et3P did
not result in enhanced reaction rates of reduction. This proves
that the large rate enhancements found with the amines are due
to their basicity and not their nucleophilicity.
+
Thus, the presence of the ammonium ion NH4 is not a
prerequisite for the fast reduction reaction.
Conclusion
During the studies of the mechanism we encountered that
the rate of reduction of 1-chlorodecane was strongly dependent
on the basicity of the amine. Although the correlation is
somewhat scattered, the stronger bases clearly give higher rates.
Aryl amines and amines with pKBH+ below 9 are not capable
of accelerating the SmI2/H2O-mediated reduction. A maximum
in the rate constant is observed with aliphatic amines having
pKBH+ in the range of 10.7 to 11.4. The more basic amine
HMDS (with a pKBH+ of 14.4) are ineffective in promoting this
reduction. It has been shown that very strongly basic amines
such as HMDS are protonated by the added water.
The strong base HMDS did not accelerate the reduction rate
despite its higher pKBH+ value. This could be due to its higher
basic strength that allows it to deprotonate water, thus removing
the coordinated water from SmI2, and thereby the high reactivity
of SmI2 is lost. The result is that SmI2(THF)5 is regenerated,
and this compound is not a powerful reductant, Scheme 4.
Scheme 4
The rate of the SmI2/H2O/amine-mediated reduction of
1-chlorodecane is first order in amine and 1-chlorodecane,
second order in SmI2, and zero order in H2O. From the studies
of 13C KIE and the reaction orders we propose that the reduction
of alkyl halides by SmI2/H2O/amine proceeds via a rate-
determining electron transfer from a dimeric SmI2(H2O) inter-
mediate to the halide. This intermediate is suggested to result
from a general base-catalyzed deprotonation of SmI2-coordinated
water. The large negative entropy of activation (-148 J K-1
mol-1) gives further indication that a large molecular assembly
occurs in the transition state. The ET appears to proceed mainly
The low number of reductive couplings that have been
observed using the SmI2/H2O/amine mixture indicates that free
radicals are reduced faster than they dimerize or undergo various
(34) Equation 3 could therefore also be expressed as rate ) Vinitial ) k′Keq[SmI2]2-
[1-chlorodecane][amine], where kobs ) k′Keq.
(35) Page, M.; Williams, A. In Organic and Bio-organic Mechanisms; Addison-
Wesley, Longman: Singapore, 1997.
(36) Bender, M. L. Chem. ReV. 1960, 60, 53. (b) Lewis, E. S. J. Phys. Org.
Chem. 1990, 3, 1. (c) Leffler, J. E. Science 1953, 117, 340. (d) Streitwieser,
Jr., A.; Kaufman, M. J.; Bors, D. A.; Murdoch, J. R.; McArtur, C. A.;
Murphy, J. T.; Shen, C. C. J. Am. Chem. Soc. 1985, 107, 6983.
(37) Dahle´n, A.; Peterson, A.; Hilmersson, G. Org. Biomol. Chem. 2003, 1,
2423-2426.
(38) Molander, G. A.; McKie J. A. J. Org. Chem. 1991, 56, 4112-4120. (b)
Curran, D. P.; Totleben, M. J. J. Am. Chem. Soc. 1992, 114, 6050-6058.
(c) Hasegawa, E.; Curran, D. P. Tetrahedron Lett. 1993, 34, 1717-1720.
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Alkyl Halide Reduction by SmI2/H2O/Amine
A R T I C L E S
with a gastight syringe through the septum, and a new spectrum was
recorded after each addition.
via an outer sphere mechanism. Daasbjerg and co-workers have
reported that the SmI2/HMPA reduction of alkyl halides
proceeds via both inner and outer sphere ET and that the outer
sphere character decreases with increasing atom number (Cl >
Br > I).30b
Preliminary results from our laboratory have shown that the
basicity of the amine used in the reagent mixture SmI2/H2O/
amine also affects the rate of reduction of conjugated olefines,
pinacol couplings, imino-pinacol couplings, intramolecular
cyclization reactions, and allyl ether clevages. The amine
dependence of the reactivity of the SmI2/H2O/amine reagent may
allow differences in selectivity when dealing with polyfunctional
substrates. Currently we are investigating if the choice of amine
also affects the selectivity in competing reactions such as
reduction vs coupling reactions.
KIE Studies. The reduction of 1-iododecane and 1-bromodecane
to decane mediated by SmI2/H2O/Et3N in THF on a 31.6 mmol scale
at 20 °C was taken to 96% and 85% conversion, respectively. Two
sets of NMR (700 µL of CDCl3 in 5 mm NMR tubes) samples were
prepared, one obtained from the partial conversion of the alkyl halide
(ca. 100 mg of 1-iododecane or 700 mg of 1-bromodecane), isolated
after extraction and distillation under reduced pressure, and the
corresponding reference samples of 1-iododecane and 1-bromodecane,
not subjected to the reaction conditions. The 13C spectra were obtained
1
at 125.703 MHz with a custom built H,13C,6Li probe (Nalorac) on a
500 MHz NMR spectrometer (Varian Unity500). NMR experiments
with 1H decoupling and NOE as well as experiments with inverse gated
1H decoupling were collected separately to obtain relative integrals
with identical results within experimental error. We used calibrated
90° pulses and >5 T1 delays (for the slowest decaying peak of in-
terest) between pulses (30 s for 1-iododecane) and a 4.99 s acquisition
time to collect 128 000 data points. The signal-to-noise-ratios were
700-1000. A zero-order baseline correction was applied for the
integrals, and the integrations were determined numerically using a
constant integration region for each peak of the references 1-iododecane
and 1-bromodecane and the recovered unreacted alkyl halide samples,
respectively.
The 2H spectra were obtained at 76.736 MHz with broadband probe
(Nalorac) on a 500 MHz NMR spectrometer (Varian Unity500). NMR
experiments with 1H decoupling and NOE as well as experiments with
inverse gated 1H decoupling were collected separately to obtain relative
integrals with identical results within experimental results. We used
calibrated 90° pulses and >5 T1 delays (for the slowest decaying peak
of interest) between pulses (30 s for 1-iododecane) and a 4.99 s
acquisition time to collect 128 000 data points. The signal-to-noise-
ratios were better than 200:1. A zero-order baseline correction was
applied for the integrals, and the integrations were determined numeri-
cally using a constant integration region for each peak of the reference
1-bromodecane and the recovered unreacted 1-bromodecane samples,
respectively.
Experimental Section
General Procedures. THF was distilled from sodium and ben-
zophenone under nitrogen atmosphere. The amines were distilled under
nitrogen atmosphere and stored over molecular sieves. SmI2, additives,
and solvents were stored under nitrogen atmosphere in a glovebox
containing typically less than 1 ppm H2O and O2, respectively.
Reductions of Alkyl Halides. In a standard initial rate measurement,
SmI2 in THF (0.11 M, 7 equiv) was added to a dry Schlenk tube, fitted
with a septum, and containing a magnetic stirrer bar, inside a glovebox
with nitrogen atmosphere. Dodecane was added to the tube, as internal
standard for the GC analysis. The amine (14 equiv) and the proton
donor, i.e., H2O (21 equiv), were added at 20.0 °C. Rate measurements
were obtained by following each reaction from approximately 1% to
5% conversion. For the Eyring plot the reaction mixtures were
equilibrated at the given temperature for 15 min before the alkyl halide
(1 equiv) was added slowly using a gastight syringe. Throughout these
studies a thermostatic bath with a temperature stability of 0.5 °C was
employed. Small portions of the mixture (200 µL) were removed via
a syringe and quenched with I2 in n-hexane (0.1 M, 0.1 mL). To the
quenched solution were added diethyl ether (1 mL) and HCl (0.12 M,
0.1 mL) to dissolve the inorganic salts and finally Na2S2O3 to remove
excess iodine. The organic layer was transferred to a vial, and the yield
of decane was analyzed with GC. An internal standard (dodecane) was
used to obtain the rate constants.
Gas Chromatography. The progress of the reaction was monitored
using a GC fitted with an achiral stationary phase column (φ ) 0.25
mm, length ) 25 m), using hydrogen as carrier gas at a flow rate of 2
mL/min and a initial column temperature of 50 °C. The injector
temperature was 225 °C. The detector temperature was 250 °C (FID).
The products were identified using authentic samples.
UV-Vis Measurements. All UV-vis spectra were recorded on a
UV-vis-NIR spectrophotometer connected to a computer. The SmI2
solutions were diluted to 3.6 mM inside a glovebox in a quartz cuvette
equipped with a screwcap fitted with a septum. The path length of the
cuvette was 1.00 cm. Successive additions of the additives were made
Acknowledgment. Mr. Roine I. Olsson is gratefully acknowl-
edged for the estimation of the pKBH+ values using the ACD-
Lab software. Prof. Robert Flowers, II and Dr. Edamana Prasad
(Lehigh University), Dr. Sten Nilsson Lill (Go¨teborg University),
and Prof. Vernon Parker (Utah State University, Logan) are
gratefully acknowledged for helpful discussions. Financial
support from the Carl Trygger Foundation and the National
Science Council (Vetenskapsrådet) is also thankfully acknowl-
edged.
Supporting Information Available: This material is available
free of charge via the Internet at http://pubs.acs.org.
JA043323U
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J. AM. CHEM. SOC. VOL. 127, NO. 23, 2005 8347