A R T I C L E S
Prasad and Flowers
Until recently, little was known about the solution structures
and energetics of Sm(II)-HMPA complexes. Upon the addition
of 4 equiv of HMPA the complex [Sm(THF)2(HMPA)4]I2 is
formed.12 Further addition of HMPA produces the octahedral
complex [Sm(HMPA)6]I2 at greater than 10 equiv of cosolvent.
On the basis of their redox potentials, both Sm-HMPA
complexes are powerful reductants. Although experimental
evidence suggests that both complexes exist in solution, a
number of questions remain, including the following: (1) How
does the successive addition of HMPA impact the rates of
reduction of alkyl halides and ketones? (2) What are the
differences between the two complexes in their interactions with
various functional groups involved in Sm-mediated reductions
and reductive coupling reactions? (3) To what degree does the
sterically demanding HMPA influence the reduction of func-
tional groups and their ability to interact with the metal center?
While the seminal studies of Curran and Dassjberg have begun
to address these questions to some degree, a thorough activation
study has not been forthcoming. Knowledge of the rate of
reduction of alkyl halides and carbonyl-containing functionalities
by SmI2 and SmI2-HMPA complexes (and the mechanism
through which they proceed) will help to establish the sequence
of events involved in these reactions. Herein we report the rates
of reduction of ketone, â-dicarbonyl substrates, and alkyl halides
by SmI2 and SmI2-HMPA complexes in THF. Activation
parameters were determined to examine the impact of HMPA
on the transition states of alkyl halide and ketone reduction.
Figure 1. Stopped flow trace showing the decay of SmI2 absorbance at
555 nm in the presence of methyl acetoacetate (0.25 M) at 25 °C. The
inset shows the same in the presence of 4 equiv of HMPA.
in eq 1. The kinetics for the alkyl iodides followed the rate law shown
-d[Sm(II) complex]/dt ) k[Sm(II) complex][ketone] (1)
in eq 2. A representative stopped flow trace for the reduction of methyl
-d[Sm(II) complex]/dt ) 2k[Sm(II) complex][alkyl iodide] (2)
acetoacetate by SmI2 and SmI2 containing 4 equiv of HMPA is
contained in Figure 1. The temperature studies used to determine
activation parameters were carried out over a range of 30-50 °C with
use of a Neslab circulator connected to the sample handling unit of the
stopped flow system. The step size used for the temperature study was
5 °C and each kinetic trace was recorded at a known temperature that
was monitored by a thermocouple in the reaction cell.
Experimental Section
Materials and General Procedures. THF was distilled from sodium
benzophenone ketyl under a nitrogen atmosphere. HMPA was dried
by vacuum distillation from CaO. Dried solvents were stored in an
Innovative Technology, Inc. drybox containing a nitrogen atmosphere
and a platinum catalyst for drying. The SmI2 was prepared according
to literature procedure13 and its concentration was determined by
iodometric titration.14 All substrates (alkyl iodides and ketones) were
received from Aldrich and distilled under vacuum from CaO before
use.
Results and Discussion
The goal of this work was to determine the rates and
activation parameters for the reduction of ketones, â-dicarbonyls,
and alkyl halides by SmI2 to examine the impact of HMPA on
the electron-transfer process. Recent work in our laboratory
showed that the SmI2-mediated reduction of ketones proceeds
through an ordered transition state.16 In particular, the presence
of a â-ester or an amide was found to enhance the rate of ketone
reduction. Subsequent activation studies provided strong evi-
dence that the reduction proceeded through a chelated transition
state. Since HMPA is known to have a high affinity for SmI2,
it is not clear whether its presence will affect the ability of a
ketone to coordinate to the Sm since a number of examples
exist that show the presence of HMPA can be deleterious to
the diastereoselectivity of samarium-induced R- and â-hydroxy
ketone-olefin couplings.17 To address this, the rates and
activation parameters for the reduction of 2-butanone, methyl
acetoacetate, and N,N-dimethylacetoacetamide by SmI2, [Sm-
(THF)2(HMPA)4]I2, and [Sm(HMPA)6]I2 were determined with
stopped-flow decay experiments (Table 1).
Stopped-Flow Rate Studies. Kinetic experiments in THF were
performed with a computer-controlled SX.18 MV stopped-flow spec-
trophotometer (Applied Photophysics Ltd. Surrey, UK). The SmI2 or
SmI2-HMPA complex and substrates were taken separately in airtight
Hamilton syringes from a drybox and injected into the stopped-flow
system. The cell block and the drive syringes of the stopped flow
reaction analyzer were flushed a minimum of three times with dry,
degassed THF to make the system anaerobic. The concentration of SmI2
used for the study was 5 mM. The concentration of the substrates was
kept high relative to [SmI2] (0.05 to 0.45 M) in order to maintain
pseudo-first-order conditions. The pseudo-first-order rate constants were
determined by using standard methods.15 Reaction rates were determined
from the decay of the SmI2 absorbance at 555 nm or the SmI2-HMPA
absorbance at 540 nm. The decay of SmI2 (or the HMPA complex)
displayed first-order behavior over >4 half-lives for all SmI2-substrate
combinations. The kinetics for the ketones followed the rate law shown
The rate constant for the reduction of 2-butanone was just
above the measured rate for the natural decay of SmI2 in THF,
but the value is consistent with the rate constant recently reported
for the reduction of 3-heptanone by SmI2.18 Addition of 4 equiv
of HMPA to the reduction enhances the rate by an order of
(11) Molander, G. A. In The Chemistry of the Metal-Carbon Bond; Hartley,
F. R., Ed.; Wiley: Chichester, UK, 1989.
(12) (a) Enemaerke, R. J.; Hertz, T.; Skrydstrup, T.; Daasbjerg, K. Chem. Eur.
J. 2000, 6, 3747. (b) Knettle, B. W.; Flowers, R. A., II Org. Lett. 2001, 3,
2321.
(13) Curran, D. P.; Gu, X.; Zhang, W.; Dowd, P. Tetrahedron 1997, 53, 9023.
(14) Shotwell, J. B.; Sealy, J. M.; Flowers, R. A., II J. Org. Chem. 1999, 64,
5251.
(15) Pedersen, S. U.; Lund, T.; Daasbjerg, K.; Pop, M.; Fussing, I.; Lund, H.
Acta Chem. Scand. 1998, 52, 657.
(16) Prasad, E.; Flowers, R. A., II J. Am. Chem. Soc. 2002, 124, 6357-6381.
(17) (a) Kawatsura, M.; Matsuda, F.; Shirahama, H. J. Org. Chem. 1994, 59,
6900. (b) Kito, M.; Sakai, T.; Yamada, K.; Matsuda, F.; Shirahama, H.
Synlett 1993, 158.
(18) Dahlen, A.; Hilmersson, G. Tetrahedron Lett. 2001, 42, 5565.
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6896 J. AM. CHEM. SOC. VOL. 124, NO. 24, 2002