Estimating the limiting reducing power of SmI2/H 2O/amine and YbI2/H2O/amine by efficient reduction of unsaturated hydrocarbons

Article abstract of DOI:10.1021/jo052268k

The mixture of samarium diiodide, amine, and water (SmI₂/H ₂O/Et₃N) is known to be a particularly powerful reductant, but until now the limiting reducing power has not been determined. A series of unsaturated hydrocarbons with varying half-wave reduction potentials (E _1/2 = -1.6 to -3.4 V, vs SCE) have been treated with SmI ₂/H₂O/Et₃N and YbI₂/H ₂O/Et₃N, respectively. All hydrocarbons with potentials of -2.8 V or more positive were readily reduced with SmI₂/H ₂O/Et₃N, whereas all hydrocarbons with potentials of -2.3 V or more positive were readily reduced using YbI₂/H ₂O/Et₃N. This defines limiting values of the chemical reducing power of SmI₂/H₂O/Et₃N to -2.8 V and of YbI₂/H₂O/Et³N to -2.3 V vs SCE.

Full text of DOI:10.1021/jo052268k

Estimating the Limiting Reducing Power of SmI2/H2O/Amine and
YbI2/H2O/Amine by Efficient Reduction of Unsaturated
Hydrocarbons
Anders Dahle´n, A° ke Nilsson, and Go¨ran Hilmersson*
Department of Chemistry, Go¨teborg UniVersity, SE-412 96 Go¨teborg UniVersity, Sweden
hilmers@chem.gu.se
ReceiVed NoVember 1, 2005
The mixture of samarium diiodide, amine, and water (SmI2/H2O/Et3N) is known to be a particularly
powerful reductant, but until now the limiting reducing power has not been determined. A series of
unsaturated hydrocarbons with varying half-wave reduction potentials (E1/2 ) -1.6 to -3.4 V, vs SCE)
have been treated with SmI2/H2O/Et3N and YbI2/H2O/Et3N, respectively. All hydrocarbons with potentials
of -2.8 V or more positive were readily reduced with SmI2/H2O/Et3N, whereas all hydrocarbons with
potentials of -2.3 V or more positive were readily reduced using YbI2/H2O/Et3N. This defines limiting
values of the chemical reducing power of SmI2/H2O/Et3N to -2.8 V and of YbI2/H2O/Et3N to -2.3 V
vs SCE.
Introduction
Flowers and Skrydstrup have independently shown that the
reducing power of SmI2 increases approximately 0.9 V (com-
pared to SmI2 in THF) by the addition of HMPA.17-20 The redox
potential (E°) for SmI2 in THF is -1.55 V vs Ag/AgNO3. In
the presence of at least 4 equiv of HMPA the redox potential
increases to -2.35 V. This increase has been attributed to the
replacement of the five THF molecules coordinated to the
samarium(II) by four HMPA molecules.21,22 The increase in
reducing power not only gives faster reactions but also affects
the chemoselectivity.23-28 The presence of HMPA and a proton
The development of new efficient synthetic methods lies at
the heart of modern organic chemistry. Even though reduction
reactions are among the most used transformations, there has
not been much focus on the development of conceptually new
methods. The most popular reagents involve hydrogen attached
to a catalyst, hydride reagents, and dissolving metals.1-4 There
are also some examples of hydrogen atom transfer reactions
such as the Meerwein-Pondorff-Verley reductions (MPV).5
However, samarium diiodide (SmI2) is rapidly becoming a
widely appreciated selective reducing agent that mediates
various important reduction and coupling reactions.6-11 The
reactions are intimately correlated with a relatively high degree
of selectivity, especially in combination with HMPA.12-16
(13) Inanaga, J.; Ishikawa, M.; Yamaguchi, M. Chem. Lett. 1987, 1485-
1486.
(14) Kagan, H. B.; Namy, J.-L. Lanthanides: Chemistry and Use in
Organic Synthesis. In Topics in Organometallic Chemistry; Kobayashi, S.,
Ed.; Springer-Verlag: Berlin, Heidelberg, 1999; Vol. 2, pp 155-198.
(15) Kim, Y. H.; Park, H. S. Synlett 1998, 261-262.
(16) Concellon, J. M.; Bardales, E. Eur. J. Org. Chem. 2004, 1523-
1526.
(17) Shabangi, M.; Flowers, R. A., II. Tetrahedron Lett. 1997, 38, 1137-
1140.
(18) Enemaerke, R. J.; Daasbjerg, K.; Skrydstrup, T. Chem. Commun.
1999, 343-344.
(19) Shabangi, M.; Kuhlman, M. L.; Flowers, R. A., II. Org. Lett. 1999,
1, 2133-2135.
(20) Enemaerke, R. J.; Hertz, T.; Skrydstrup, T.; Daasbjerg, K. Chem.
Eur. J. 2000, 6, 3747-3754.
(21) Hou, Z.; Wakatsuki, Y. J. Chem. Soc., Chem. Commun. 1994, 1205-
1206.
(22) Evans, W. J.; Gummersheimer, T. S.; Ziller, J. W. J. Am. Chem.
Soc. 1995, 117, 8999-9002.
(23) Shie, J.-J.; Workman, P. S.; Evans, W. J.; Fang, J.-M. Tetrahedron
Lett. 2004, 45, 2703-2707.
* To whom correspondence should be addressed. Ph: +46-(0)31-7722904.
Fax: +46-(0)31-7723840.
(1) Caine, D.; Chao, S. T.; Smith, H. A. Org. Synth. 1977, 56, 52-58.
(2) Magoon, E. F.; Slaugh, L. H. Tetrahedron 1967, 23, 4509-4515.
(3) Lindlar, H.; Dubuis, R. Org. Synth. 1973, V, 880.
(4) Siegel, S.; Smith, G. V. J. Am. Chem. Soc. 1960, 82, 6082-6087.
(5) Evans, D. A.; Nelson, S. G.; Gagne, M. R.; Muci, A. R. J. Am. Chem.
Soc. 1993, 115, 9800-9801.
(6) Kagan, H. B. Tetrahedron 2003, 59, 10351-10372.
(7) Krief, A.; Laval, A.-M. Chem. ReV. 1999, 99, 745-777.
(8) Molander, G. A. Chem. ReV. 1992, 92, 29-68.
(9) Molander, G. A. Org. React. (N. Y.) 1994, 46, 211-367.
(10) Molander, G. A.; Harris, C. R. Tetrahedron 1998, 54, 3321-3354.
(11) Dahlen, A.; Hilmersson, G. Eur. J. Inorg. Chem. 2004, 3393-3403.
(12) Otsubo, K.; Inanaga, J.; Yamaguchi, M. Tetrahedron Lett. 1986,
27, 5763-5764.
10.1021/jo052268k CCC: $33.50 © 2006 American Chemical Society
Published on Web 01/17/2006
1576
J. Org. Chem. 2006, 71, 1576-1580

Reducing Power of SmI2/H2O/Amine and YbI2/H2O/Amine
SCHEME 1. Suggested Mechanism for the Reduction of an Unsaturated Hydrocarbon
source in Ln(II) solutions also facilitates reduction of functional
groups that are more difficult to reduce, e.g., alkyl halides.13
There are reports in which other additives have been introduced
because of the carcinogenic nature of HMPA.29-33 In this context
we have discovered that a combination of an amine, water, and
SmI2 results in a very potent reducing agent. The reagent mixture
SmI2/water/amine not only mediates instantaneous reductions
of ketones and R,â-unsaturated esters and rapid reduction of
halides (iodides, bromides, and chlorides) and conjugated
alkenes but also effects coupling of aryl ketones and aryl imines
and induces cleavage of allyl ethers.24,34-39
The use of SmI2 has previously been focused mainly on
radical coupling reactions, but the discovery of the SmI2/water/
amine mixtures has made SmI2 a promising alternative to
hydrides and hydrogen as a result of its mild but extremely fast
reactions, as well as clean and simple workup procedures. The
only requirement is that the reaction mixture is completely
oxygen-free. Another advantage with SmI2 is that it is not
pyrophoric and does not require addition of a toxic transition
metal such as palladium. (It has been proven in several health
studies that certain metals, e.g., palladium in dental alloys, may
cause illness, periodontal disease and poisoning.)
Recently, our group published a detailed kinetic study on the
reduction of alkyl halides by SmI2/H2O/amine and suggested a
mechanism for the rapid reductions.40 It was shown that the
rate of reduction is dependent on the basicity of the amine and
that the transition state most likely consists of a dimeric SmII
species. However, efforts to determine the redox potential of
SmI2/H2O/amine by cyclic voltammetry were not completely
successful.38 The oxidation of SmII to SmIII was irreversible,
and it was not possible to obtain information on the reducing
power of this potent reagent mixture.
the reactivity of Ce, Nd, Sm, and Yb with the reduction
potentials of the hydrocarbons.41 They found that the chemical
reduction fits with standard electrochemical reductions for the
first half-wave (E1/2) of the hydrocarbons. A few years later,
Evans and co-workers reported that decamethylsamarocene, (C5-
Me5)2Sm, reacts with several polycyclic aromatic hydrocar-
bons.42 From the potentials of the polycyclic compounds it was
observed that (C5Me5)2Sm reacts with polycyclic aromatics that
have half-wave potentials equal to or more positive than -2.22
V, vs SCE. In 2001, Fedushkin and co-workers used the same
concept to probe the reactivity of thulium diiodide (TmI2),43
which is known to have a redox potential, E°(MIII/MII), of -2.3
V vs SCE. On the basis of the reduction potentials of the
hydrocarbons they estimated the effective chemical reducing
power of TmI2 to be approximately -2.0 V, vs SCE. These
studies, by Chauvin, Evans, and Fedushkin with co-workers,
give an estimate of the reducing powers for various lanthanide
reagents, and it is clear that this method offers a rough
approximation of the reactivity of the reagents when used in a
series of similar compounds, even though the reactions were
run in a different medium (THF rather than DMF).
It is important that only unsaturated hydrocarbons, containing
nothing else but carbons and hydrogens, are used in these
studies. Otherwise the substrate itself could compete with the
bulk solvent THF for coordination with the lanthanide(II) to
change the reaction mechanism from an outer- to an inner-sphere
electron transfer (ET). The chemical reduction of, e.g., an
aromatic compound such as benzene, would require two
electrons and two protons to be completed (Scheme 1). The
first electron transfer to the hydrocarbon occurs via an outer-
sphere ET and this step should be the rate-determining step,
since the aromaticity is lost in such a process.
Chauvin and co-workers reported in the late 1980s the rare
earth metal reduction of unsaturated hydrocarbons and correlated
Herein, we report on the high reducing power of SmI2/water/
amine and YbI2/water/amine in the reduction of unsaturated
hydrocarbons having E1/2 values in the range -1.6 to -3.4 V
vs SCE.
(24) Kim, M.; Knettle, B. W.; Dahlen, A.; Hilmersson, G.; Flowers, R.
A., II. Tetrahedron 2003, 59, 10397-10402.
(25) Knettle, B. W.; Flowers, R. A., II. Org. Lett. 2001, 3, 2321-2324.
(26) Riber, D.; Hazell, R.; Skrydstrup, T. J. Org. Chem. 2000, 65, 5382-
5390.
Results and Discussion
(27) Molander, G. A.; Harris, C. R. J. Org. Chem. 1997, 62, 2944-
A large number of unsaturated hydrocarbons and alkylhalides,
with their first half-wave potentials, E1/2, ranging from -1.6 to
-2.8 V vs SCE, were observed to be quantitatively reduced
using SmI2/H2O/pyrrolidine (Figure 1 and Table 1). Benzene,
with an E1/2 of -3.4 V, was not reduced. This gives an estimate
of the chemical reduction potential in the range of -2.8 to -3.4
V. However, it is most likely closer to -2.8 V since the
reduction of 1-chlorodecane occurs at a very slow rate in
comparison with other substrates.
2956.
(28) Shiue, J. S.; Lin, C. C.; Fang, J. M. Tetrahedron Lett. 1993, 34,
335-338.
(29) Fuchs, J. R.; Mitchell, M. L.; Shabangi, M.; Flowers, R. A., II
Tetrahedron Lett. 1997, 38, 8157-8158.
(30) Cabri, W.; Candiani, I.; Colombo, M.; Franzoi, L.; Bedeschi, A.
Tetrahedron Lett. 1995, 36, 949-952.
(31) Hasegawa, E.; Curran, D. P. J. Org. Chem. 1993, 58, 5008-5010.
(32) Machrouhi, F.; Namy, J.-L. Tetrahedron Lett. 1999, 40, 1315-1318.
(33) Inanaga, J.; Sakai, S.; Handa, Y.; Yamaguchi, M.; Yokoyama, Y.
Chem. Lett. 1991, 2117-2118.
(34) Dahlen, A.; Hilmersson, G. Tetrahedron Lett. 2002, 43, 7197-7200.
(35) Dahlen, A.; Sundgren, A.; Lahmann, M.; Oscarson, S.; Hilmersson,
G. Org. Lett. 2003, 5, 4085-4088.
(36) Dahlen, A.; Hilmersson, G. Tetrahedron Lett. 2003, 44, 2661-2664.
(37) Dahlen, A.; Hilmersson, G. Chem. Eur. J. 2003, 9, 1123-1128.
(38) Dahlen, A.; Hilmersson, G.; Knettle, B. W.; Flowers, R. A. J. Org.
Chem. 2003, 68, 4870-4875.
(39) Dahlen, A.; Petersson, A.; Hilmersson, G. Org. Biomol. Chem. 2003,
1, 2423-2426.
(40) Dahlen, A.; Hilmersson, G. J. Am. Chem. Soc. 2005, 127, 8340-
8347.
We recently reported that the basicity of the amine affects
the rate of reduction of alkyl halides.40 Replacement of
(41) Chauvin, Y.; Olivier, H.; Saussine, L. Inorg. Chim. Acta 1989, 161,
45-47.
(42) Evans, W. J.; Gonzales, S. L.; Ziller, J. W. J. Am. Chem. Soc. 1994,
116, 2600-2608.
(43) Fedushkin, I. L.; Bochkarev, M. N.; Dechert, S.; Schumann, H.
Chem. Eur. J. 2001, 7, 3558-3563.
J. Org. Chem, Vol. 71, No. 4, 2006 1577

Dahle´n et al.
FIGURE 1. Unsaturated hydrocarbons used in this study together with their half reduction potentials, E1/2, in DMF.
TABLE 1. Reduction of Hydrocarbons with LnI2/H2O/Aminea
major product using
SmI2/H2O/amine
(% of product mixture)
major product using
YbI2/H2O/amine
(% of product mixture)
-E1/2
entry
substrate
(V)b
1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
16
azulene
tetrahydroazulene (40)
acenaphtene (95)
cyclooctadiene (95, three isomers)
9,10-dihydroanthracene (99)
bibenzyl (99)
dihydroazulene (95, four isomers)
acenaphtene (99)
cyclooctadiene (95, three isomers)
9,10-dihydroanthracene (99)
stilbene (95) + bibenzyl (trace)
bibenzyl (99)
decane (99)
no reaction
no reaction
no reaction
no reaction
no reaction
no reaction
no reaction
trace (<0.4)
no reaction
1.6342
1.6542
1.8342
1.9842
2.1144
2.2145
2.3046
2.4047
2.4645
2.4645
2.5048
2.5145
2.6045
2.6545
2.846
acenaphthylenec
cyclooctatetraene
anthracenec
diphenylacetylenec
trans-stilbenec
decyl bromidec
p-terphenyld
bibenzyl (99)
decane (99)
dihydro-p-terphenyl (75, three isomers)
dihydrotriphenylene (70)
9,10-dihydrophenanthrene (95)
dihydrotriphenylbenzene (85, two isomers)
1,4-dihydronaphthalene (78)
dihydrobiphenyl (63, two isomers)
ethylbenzene (99)
triphenylene
phenanthrenec
1,3,5-triphenylbenzenee
naphthalene
biphenyl
styrenec
decyl chloride
benzene
decane (99)
no reaction
3.4245
a LnI2 (10 equiv), amine (20 equiv), and substrate (1 equiv) were mixed, and finally H2O (30 equiv) was added. Samples were taken from the reaction
vessel within 5 min. Products were analyzed by GC-MS. Comparable product distribution is achieved with triethylamine with pyrrolidine as amine. b Versus
SCE. The accuracy of these values is approximately (0.1 V due to solvent effects. c SmI2 (2.5 equiv), amine (5.0 equiv), and substrate (1.0 equiv) were
mixed, and finally H2O (7.5 equiv) was added. Twice the amounts of reagents were used with diphenylacetylene for full reduction to bibenzyl. d Measured
in dimethylamine/TBABr instead of DMF. e This value was recalculated from -3.08 V vs Ag/AgNO3 to -2.50 vs SCE according to refs 17-19 and 49.
pyrrolidine with triethylamine gave the same result, although
the unsaturated compounds were reduced at a much slower rate.
Overall the reagent mixtures lead only to reduction without
coupling reactions taking place.
Depending on the nature of the unsaturated hydrocarbon, there
is varying selectivity between different double bonds, which
gives rise to different product distribution. It appears that
reduction of polyaromatic hydrocarbons (PAH) with fused rings,
such as anthracene and phenanthrene, gives one product
preferentially (Scheme 2), whereas aromatics with single bond
connected rings as in biphenyl and p-terphenyl give a mixture
of several isomeric products. For this reason, the synthetic use
is limited to fused PAHs. Nevertheless, the substrates in Table
1 still serve as indicators of the reducing abilities of various
reducing agents.
Since an excess of SmI2 has been used throughout the study,
over-reduction is apparent in several cases. Therefore, some
substrates yield complex product mixtures upon reduction.
However, the formation of product mixtures can be expected
on the basis of previous results.36 Styrene derivatives are
particularly easy to be reduced, whereas isolated double bonds
are not reduced.
1578 J. Org. Chem., Vol. 71, No. 4, 2006

Reducing Power of SmI2/H2O/Amine and YbI2/H2O/Amine
SCHEME 2. Reduction of Fused PAHs a-d Gives One
Preferred Product
FIGURE 2. log(rel.rate) vs -E1/2 for acenaphthylene, anthracene, and
styrene with SmI2/H2O/Et3N (s) and for acenaphthylene, anthracene,
and 1-bromodecane with YbI2/H2O/pyrrolidine (- - -).
SCHEME 3. Reduction of Naphthalene by Excess SmI2/
Water/Pyrrolidine, Yielding a Mixture of 1,4-Dihydro- and
1,2,3,4-Tetrahydronaphthalene
The chemical reducing power of the considerably weaker
reducing agent YbI2 (E1/2 ) -1.02 V vs Ag/AgNO3)50 was also
evaluated in reductions of the PAHs. All unsaturated hydro-
carbons with reduction potentials E1/2 ranging from -1.6 to
-2.30 V (vs SCE) were quantitatively reduced (Table 1). The
alkyl halide decyl bromide was also efficiently reduced (entry
8). Interestingly, decyl chloride having significantly more
negative reduction potential (-2.8 V) appears to undergo some
reaction, although it only gave trace amounts (<0.4%) of the
corresponding decane with a large excess of YbI2 (10 equiv).
The less reactive YbI2/water/amine mixtures resulted in product
mixtures somewhat less complex than those obtained using
SmI2/water/amine. SmI2/water/amine is a more powerful re-
ductant than YbI2/water/amine. The substrates that have very
similar reduction potentials for different double bonds and may
undergo successive reductions are therefore more likely to yield
more complex product mixtures in the case of using, e.g., excess
SmI2/water/pyrrolidine.
It was also validated that the half-wave potential of different
unsaturated hydrocarbons correlated with the relative rate of
reduction, i.e., the rate increases as the potential of the
hydrocarbon becomes more positive. The logarithm of the
relative rates of reduction (log(rel.rate)) were plotted versus the
redox potentials (-E1/2) of a few hydrocarbons (Figure 2). This
gave a linear or nearly linear correlation between the rate and
We propose that the reduction of the unsaturated hydrocar-
bons proceeds successively, with the first electron transfer being
rate-determining, as illustrated for naphthalene in Scheme 3.
There are no observable H2O/D2O kinetic isotope effects;36
hence the protonation steps are considered very fast and have
been left out for clarity. The mechanism for olefin reduction is
likely similar to that for alkyl halides, both involving a slow
outer-sphere ET from SmII to the substrate.40
E
1/2. Therefore, the reaction most likely proceed through outer-
sphere electron transfer (ET).40,51-56
(44) Sioda, R. E.; Cowan, D. O.; Koski, W. S. J. Am. Chem. Soc. 1967,
89, 230-234.
(45) Ruoff, R. S.; Kadish, K. M.; Boulas, P.; Chen, E. C. M. J. Phys.
Chem. 1995, 99, 8843-8850.
(46) Barber, J. J.; Whitesides, G. M. J. Am. Chem. Soc. 1980, 102, 239-
243.
Conclusion
(47) Meerholz, K.; Heinze, J. J. Am. Chem. Soc. 1989, 111, 2325-2326.
(48) Shriver, D. F.; Smith, D. E.; Smith, P. J. Am. Chem. Soc. 1964, 86,
5153-5160.
In our preceding studies, the versatility of the powerful
reagent mixture SmI2/H2O/amine has been proven in several
types of reductions and coupling reactions. However, even
though the mechanism of this reagent mixture is nowadays
reasonably clear, the reducing power has until now been
unknown. Comparison of several unsaturated hydrocarbons, with
known E1/2 values, provided us with a chemical limit of the
effective reducing power for both SmI2/H2O/amine and YbI2/
H2O/amine. The approximate limiting values for SmI2/H2O/
amine and YbI2/H2O/amine are -2.8 V and -2.3 V vs SCE,
(49) Prasad, E.; Knettle, B. W.; Flowers, R. A., II. J. Am. Chem. Soc.
2002, 124, 14663-14667.
(50) Dahlen, A.; Prasad, E.; Flowers, R. A., II; Hilmersson, G. Chem.
Eur. J. 2005, 11, 3279-3284.
(51) Save´ant, J.-M. J. Am. Chem. Soc. 1987, 109, 6788-3795.
(52) Andrieux, C. P.; Gallardo, I.; Save´ant, J.-M. J. Am. Chem. Soc. 1989,
111, 1620-1626.
(53) Albery, W. J. Annu. ReV. Phys. Chem. 1980, 31, 227-263.
(54) Jordan, R. B. Topics in Inorganic Chemistry: Reaction Mechanisms
of Inorganic and Organometallic Systems; Oxford University Press: New
York, 1998; pp 188-220.
(55) Eberson, L. AdVances in Physical Organic Chemistry: Electron-
Transfer Reactions in Organic Chemistry; Academic Press: London, 1982;
pp 79-185.
(56) Fukuzumi, S.; Wong, C. L.; Kochi, J. K. J. Am. Chem. Soc. 1980,
102, 2928-2939.
J. Org. Chem, Vol. 71, No. 4, 2006 1579

Dahle´n et al.
To avoid over-reduction of substrates with fused rings (e.g.,
acenaphthylene), only 2.5 equiv of SmI2, 5.0 equiv of amine and
7.5 equiv of water should be used for reduction.
Small portions of the reaction mixture (200 µL) were removed
with a gastight syringe within 5 min and quenched by air. To the
quenched solution were added diethyl ether (1 mL) and HCl (0.1
M, 0.1 mL) (to dissolve the inorganic salts), and finally a few drops
of saturated Na2S2O3 were added to remove excess iodine. The
organic layer was transferred to a vial and the product composition
was analyzed with GC and GC-MS.
respectively. Thus, the reducing powers have increased for about
1.8 V upon mixing them with water and amine. Since all
reported E1/2 values are measured in DMF, not THF, the exact
values should be treated as rough estimates.
For synthetic purposes the LnI2/H2O/amine mixtures are well
suited for the reduction of aromatic substrates with fused rings
such as phenantrene, anthracene, and acenaphthylene, since only
one major reduction product is formed. Unsaturated hydrocar-
bons with linked rings, as in for example biphenyl derivatives,
usually give mixtures of isomers as reduction products.
Gas Chromatography. The progress of the reaction was
monitored using a GC fitted with a low-bleed achiral stationary
phase (fused silica) column (φ ) 0.25 mm, length ) 25 m), using
nitrogen as carrier gas at a flow rate of 1 mL/min and an initial
column temperature of 70 °C. The temperature program increased
with a 10 °C/min to a final temperature of 300 °C. The injector
temperature was 225 °C. The detector temperature was 250 °C
(FID). The products were identified using GC-MS and/or authentic
samples.
Experimental Section
General. THF was distilled from sodium and benzophenone
under nitrogen atmosphere. The amines were distilled under nitrogen
atmosphere. SmI2, additives, and solvents were stored under
nitrogen atmosphere in a glovebox containing typically less than 1
ppm H2O and O2, respectively.
Reductions of Unsaturated Hydrocarbons. In a standard
reduction, SmI2 in THF (0.11 M, 10 equiv) was added to a dry
Schlenk tube or round-bottomed flask, fitted with a septum and
containing a magnetic stirrer bar, inside a glovebox with nitrogen
atmosphere. The substrate (1 equiv) was added to the solution
followed by the amine (20 equiv) and H2O (30 equiv) at ambient
temperature. The large excess of reagents was used to facilitate
evaluation of the product distribution of multiply reduced samples.
Acknowledgment. Financial support from AstraZeneca
R&D Mo¨lndal and the National Research Council (Veten-
skapsrådet) is gratefully acknowledged. We are also grateful to
Prof. Elisabet Ahlberg for fruitful discussions.
JO052268K
1580 J. Org. Chem., Vol. 71, No. 4, 2006