On the role of samarium/HMPA in the post electron-transfer steps in Sml2 reductions

Article abstract of DOI:10.1021/ol7029883

The reaction of p,p-dichlorobenzophenone with Sml₂ was studied in the presence of variable amounts of HMPA. The electron-transfer step takes place instantaneously. In the presence of excess substrate, the addition of HMPA retarded the rate of c

Full text of DOI:10.1021/ol7029883

ORGANIC
LETTERS
2008
Vol. 10, No. 5
865-867
On the Role of Samarium/HMPA in the
Post Electron-Transfer Steps in SmI2
Reductions
Hani Farran and Shmaryahu Hoz*
Department of Chemistry, Bar-Ilan UniVersity, Ramat-Gan 52900, Israel
shoz@mail.biu.ac.il
Received December 12, 2007
ABSTRACT
The reaction of p,p′-dichlorobenzophenone with SmI2 was studied in the presence of variable amounts of HMPA. The electron-transfer step
takes place instantaneously. In the presence of excess substrate, the addition of HMPA retarded the rate of coupling to pinacol by a factor
of 250. In the presence of an excess of SmI2, the initial rate retardation is followed by a dramatic increase in rate.
The chemistry of SmI2 is highly sensitive to various additives.
Therefore, one of the main foci of studies in recent years
has been the improvement of reactivity, chemoselectivity,
and stereoselectivity by additives.1 Since the discovery by
Inanaga,2 HMPA became one of the most important additives
in the chemistry of SmI2.3
The principal findings regarding this agent are: (a) the
formation of a tetra-coordination complex4 and hexa-coor-
dination complex5 with SmI2, which has a dramatic effect
on the rate of electron transfer and regio and stereo selec-
tivities;1b,6 (b) the work by Flowers,7 by Hilmersson,8 and
by Skrydstrup and Daasbejerg9 indicated that complexation
by HMPA is accompanied by a marked increase (0.90 V) in
the reduction potential of the SmI2; (c) the reactivity order
is hexa > tetra > 0 HMPA coordinated SmI2;9 and (d) evi-
dence was provided for the ionic character of these com-
plexes.9
Contrary to the consensus that HMPA facilitates the reac-
tions of SmI2, we show in this paper that, in certain cases,
(4) Hou, Z.; Wakatsuki, Y. J. Chem. Soc., Chem. Commun. 1994, 1205-
1206.
(5) Hou, Z.; Zhang, Y.; Wakatsuki, Y. Bull. Chem. Soc. Jpn. 1997, 70,
149-153.
(6) (a) Molander, G. A.; McKie, J. A. J. Org. Chem. 1992, 57, 3132-
3139. (b) Molander, G. A. Org. React. 1994, 46, 211-367, and references
cited therein.
(7) (a) Shabangi, M.; Flowers, R. A. Tetrahedron. Lett. 1997, 38, 1137-
1140. (b) Shotwell, J. B.; Sealy, J. M.; Flowers, R. A. J. Org. Chem. 1999,
64, 5251-5255.
(8) Dahlen, A.; Hilmersson, G. Eur. J. Inorg. Chem. 2004, 17, 3393-
3403.
(9) Enemærke, R. J.; Hertz, T.; Skrydstrup, T.; Daasbjerg, K. Chem.-
Eur. J. 2000, 6, 3747-3754.
(1) For some recent reviews, see: (a) Edmonds, D. J.; Johnston, D.;
Procter, D. J. Chem. ReV. 2004, 104, 3371-3403. (b) Kagan, H. B. Tetrahe-
dron 2003, 59, 10351-10372. (c) Steel, P. G. J. Chem. Soc., Perkin Trans.
1 2001, 2727-2751. (d) Krief, A.; Laval, A.-M. Chem. ReV. 1999, 99, 745-
777. (e) Molander, G. A.; Harris, C. R. Tetrahedron 1998, 54, 3321-3354.
(f) Molander, G. A.; Harris, C. R. Chem. ReV. 1996, 96, 307-338. (g)
Dahlen, A.; Hilmersson, G. Tetrahedron Lett. 2001, 42, 5565-5569.
(2) Inanaga, J.; Ishikawa, M.; Yamaguchi, M. Chem. Lett. 1987, 1485-
1486.
(3) (a) Kawaji, T.; Hayashi, K.; Hashimoto, I.; Matsumoto, T.; Thiemann,
T.; Mataka, S. Tetrahedron. Lett. 2005, 46, 5277-5279. (b) Pospisil, J.;
Pospisil, T.; Marko, I. E. Org. Lett. 2005, 7, 2373-2376. (c) Concellon, J.
M.; Bardales, E. Eur. J. Org. Chem. 2004, 7, 1523-1526.
10.1021/ol7029883 CCC: $40.75
© 2008 American Chemical Society
Published on Web 02/02/2008

HMPA slows down the reactions and also changes their
course.
One of the classical uses of SmI2 is the reduction of
carbonyl compounds. Herein we present results obtained in
the reduction (eq 1) of p,p′-dichlorobenzophenone (1). The
reactions were followed at the λmax (580 nm) of the radical
anion using stopped flow spectroscopy.
In the present case, the Sm+3 provides the necessary
bridging. However, an increased amount of HMPA coordi-
nating to the Sm+3 reduces the concentration of Sm+3 avail-
able for the bridging, and therefore, ultimately, the reaction
rates decrease. At the plateau ([HMPA] g 20 mM), the
bridging is achieved, probably by an addition-elimination
sequence displacing some HMPA molecules from the
samarium in a rate determining step.
Reactions in the Presence of TFE. In previous work,12
we have shown that because of the weak basicity of the
radical anion, protonation by TFE in this relatively apolar
medium (THF) is highly endothermic. The protonation is
energetically enabled by the Sm+3 cation stabilization of the
generated alkoxide. This stabilization is equivalent to an in-
crease of the acidity of the alcohol by ca. 11 orders of mag-
nitude.13 Most likely, the hard Sm+3 departs from the soft
radical anion, in a square transition state, and moves to the
hard alkoxide generated in the course of the protonation (eq
3). However, relatively high concentrations of HMPA reduce
the concentration of the Sm+3 available to sustain the proto-
nation process, and therefore, the reaction rate is decreased.
This substrate was chosen for this study rather than the
unsubstituted benzophenone because of its high electron
affinity, which results in its complete conversion to the
radical anion at the dead time of the mixing. (Concentrations
used: [SmI2] ) 2.5 mM; [Ar2CdO] ) 50 mM in THF.)
The reaction in the absence of a proton donor was second
order (k1) in the radical anion, as expected for a coupling
reaction. Addition of trifluoroethanol (TFE) to the reaction
mixture resulted in first-order kinetics in the radical anion
(k2) and first order in the TFE.
Table 1 and Figures S1 and S2 (see Supporting Informa-
tion) demonstrate the unusual effect HMPA has on the rate
of the reaction of 1 in the presence of excess substrate over
SmI2.
Table 1. Rate Constants for the Reaction of SmI2 (2.5 mM)
with 1 (50 mM) in the Presence and in the Absence of TFE as a
Function of HMPA Concentration
In the presence of 25 mM TFE, the radical obtained mainly
dimerizes to furnish pinacol (eq 4).
no TFE
[HMPA] (mM)
[TFE] ) 25 mM
[HMPA] (mM) )
k2 (s-1
k1 (M-1s-1
)
0
8
1500
30
0
8
5.8
0.4
16
20
30
40
50
7
16
20
30
40
50
0.08
0.075
0.07
0.064
0.065
6.5
6.2
6.15
6.1
It should be noted that a ca. 10 fold rate drop was
also observed in the reduction of 1-iodobutane by [Sm-
{N(SiMe3)2}2] as a result of adding HMPA to the reaction
mixture. However, it was concluded that the rate retardation
originates from hindered access at the electron-transfer step.14
The picture becomes more complicated when SmI2 is
present in excess.15 The drop in reaction rates is still
observed. However, this rate depression is followed by an
upward surge of the rate as the concentration of the HMPA
is further increased (Table 2, Figures 1 and 2).
Increasing the concentration of HMPA results in a dra-
matic decrease of rates. The coupling reaction in the absence
of proton donor is slowed down by a factor of ca. 250 and
in the presence of TFE by a factor of ca. 80. The most
plausible explanation of this is that the Sm+3 generated in
the electron-transfer step is essential for the subsequent steps
of the reactions, and its intensive complexation of HMPA
apparently prevents it from fulfilling its role in these steps.
In the absence of proton donor and for low concentration
of HMPA, the reaction is second order in the radical anion
Reactions in the Absence of TFE. Because of the
Coulombic repulsion between the two negatively charged
oxygen atoms in the radical anions, in the absence of protons
to neutralize the negative charges,10 bridging by a di- or tri-
valent metal cation (eq 2) is essential for pinacol formation.
Mono-valent cations such as Na+ fail to produce “even a
trace of pinacol.”11
(10) Kleiner, G.; Tarnopolsky, A.; Hoz, S. Org. Lett. 2005, 7, 4197-
4200.
(11) Bachmann, W. E. J. Am. Chem. Soc. 1933, 55, 1179-1188.
(12) Tarnopolsky, A.; Hoz, S. J. Am. Chem. Soc. 2007, 129, 3402-
3407.
(13) Neverov, A. A.; Gibson, G.; Brown, R. S. Inorg. Chem. 2003, 42,
228-234.
(14) Prasad, E.; Knettle, B. W.; Flowers, R. A. J. Am. Chem. Soc. 2004,
126, 6891-6894.
866
Org. Lett., Vol. 10, No. 5, 2008

However, a further increase in the HMPA concentration
induces the formation of SmI2(HMPA)6 with an increased
reduction potential,9 which leads to the formation of the
dianion (eq 5). The latter, presumably, rapidly abstracts a
proton from THF16 to yield the hydrol as the major product
(93% + 7% starting material) at 40 mM HMPA.
Table 2. Rate Constants for the Reaction of SmI2 (10 mM)
with 1 (2 mM), in the Presence and in the Absence of TFE, as a
Function of HMPA Concentration
no TFE
[HMPA] (mM)
[TFE] ) 25 mM
[HMPA] (mM) )
k4 (s-1
k3 (M-1s-1
)
In the presence of TFE, a similar mechanistic variation
takes place. At low HMPA concentrations, there is enough
“free” Sm+3 to enable efficient protonation, hence the first
order in the radical anion (k4) and in the proton donor. At
higher concentrations of HMPA, protonation of the radical
anion becomes relatively inefficient due to the depletion of
the “free” Sm+3 to support it, and as a result of this, the rate
decreases. A further increase of the concentrations of HMPA
induces the formation of the very basic dianion. This step
becomes rate determining because the protonation of this
highly basic species is very rapid and does not necessitate
any assistance from Sm+3, thus rendering the reaction to be
zero order in the proton donor.
0
4
8
100
80
21
0
4
8
16
20
30
40
50
3.6
2.8
0.6
0.25
0.23
0.34
0.9
16
18
k5 (s-1
0.28
2.3
)
30
40
50
5.8
3.1
(k3), in line with the above discussion for the coupling
reaction. However, at higher concentrations of HMPA, the
reaction becomes first order (k5) in the radical anion.
An additional indication for the involvement of SmI2-
(HMPA)6 (or other complexes with reducing power higher
than that of SmI2(HMPA)4) is the rate retardation observed;
when at a high concentration of HMPA (40 mM), the
concentration of SmI2 is increased. Thus, in the absence of
a proton donor, the rate constant for [SmI2] ) 12 mM is
0.86 s-1 and it decreases to 0.52 s-1 for [SmI2] ) 19 mM.
This is simply because the surplus of HMPA used to generate
the SmI2(HMPA)6 is used now to coordinate the added SmI2.
To the best of our knowledge, this is the first report on
the kinetics of the post electron-transfer events in the
reduction of carbonyl compounds by SmI2. This work shows
that both Sm+3 and HMPA play an important role in this
regime of the reaction and that it is possible to control the
interplay between the effects of “free” and complexed Sm+3
using HMPA to affect the rates, the mechanistic course, and
the products obtained in these reactions. This is nicely
exemplified by the fact that high quantities of pinacol are
always obtained in the absence of HMPA. However, in the
presence of an excess of HMPA and SmI2, hydrol is the only
product, even in the absence of TFE.
Figure 1. Log-log plot of the dependence of the rate constants
for the reaction of SmI2 with 1 as a function of HMPA concentra-
tion.
Addition of small quantities of HMPA reduces the rate
because of the depletion of “free” Sm+3 as stated above.
Supporting Information Available: Technical data and
Figures S1 and S2. This material is available free of charge
via the Internet at http://pubs.acs.org.
OL7029883
(15) The reactions in this case were analyzed as first order reactions. In
an ideal situation, a 10-fold excess is needed for a pseudo first order analysis.
However, because reliable kinetic measurements could be obtained only
below 1 O.D., the maximum concentration of SmI2 that could be used in
these reactions was 0.01 M. Moreover, because of traces of water present
in the solution, the concentration of the substrate was maintained above
0.002 M. Thus, the relative change in the reagent in excess SmI2, instead
of changing from 10 to 9, is changed from 8 to 6. In spite of that, reasonable
first order rate constants were obtained.
Figure 2. Log-log plot of the dependence of the rate constants
for the reaction of SmI2 with 1 as a function of HMPA concentration
in the presence of TFE.
(16) Clayden, J.; Yasin, S. A. New J. Chem. 2002, 26, 191-192.
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