2
T. V. Chciuk et al. / Tetrahedron Letters xxx (2015) xxx–xxx
donors may coordinate to Sm(II) as well as donate a proton
through heterolytic cleavage of the O–H bond and these processes
may be coupled. As a consequence, proton donors are typically
placed in two categories, those which form ground state complexes
with SmI2 (water, methanol, glycols) and those which do not
(t-BuOH, and 2,2,2-trifluoroethanol, etc.).10e,18
Lewis bases can also be employed with coordinating proton
donors.11a Seminal work in this area was carried out by Hilmersson
who discovered that the combination of SmI2 with water and
amines produced a powerful reductant capable of reducing a wide
range of functional groups.19 Procter and co-workers have recently
expanded on Hilmersson’s work employing the reducing system
for the reduction of a range of carboxylic acid derivatives.20 During
recent studies of this method, we considered a range of amines and
approaches for mimicking the system with a common and inex-
pensive reagent. We were intrigued by the additive N,N-
dimethyl-2-aminoethanol (DMAE) since it contained a proton
donor and amine. In addition, we reasoned that it should have a
high affinity as a chelating ligand and as a consequence have the
potential for high reactivity at relatively low concentrations. Care-
ful inspection of the literature shows that the additive has been
Scheme 1.
In considering the possible mechanism of the reduction, there
are several possibilities as displayed in Scheme 1: (1) DMAE is act-
ing as a chelating proton donor (i.e., ethylene glycol) and electron
transfer (ET) to substrate precedes proton transfer (PT), (2) DMAE
coordinates to Sm(II) through oxygen and deprotonation of the
O–H occurs through an intramolecular process followed by ET to
substrate, or (3) DMAE chelates to Sm(II) and deprotonation occurs
by another equivalent of additive followed by ET to substrate.
To obtain more insight into the mechanism of the reduction of
substrate by SmI2–DMAE, the rate of reduction of anthracene and
rate orders for the components were determined under pseudo
first order conditions by monitoring the decay of SmI2 in THF at
25 °C. Anthracene was chosen as the substrate to simplify the anal-
ysis since it is unlikely to coordinate to Sm(II). The stability of
SmI2–DMAE under experimental conditions used in the rate stud-
ies was determined by measuring the decay of the reagent combi-
nation in the absence of anthracene. The natural decay was
determined to be less than 1% of that obtained in the presence of
anthracene (see Supplementary material). A representative decay
for the reduction of anthracene by SmI2–DMAE is shown in Fig-
ure 1. The decay of SmI2 displayed first-order behavior over >4 half
lives for all SmI2–DMAE–anthracene combinations. The rate con-
stant and rate orders for each component are contained in Table 2.
To acquire a more detailed insight into the electron transfer
process for the reduction of anthracene by SmI2–DMAE, rates were
measured over a temperature range to obtain activation enthalpy
employed in the selective opening of
a,b-epoxy esters and 2-acy-
laziridines, aziridine-2-carboxylates, and aziridine-2-carboxam-
ides to b-hydroxy esters and b-aminocarbonyls, respectively.21
Interestingly, the additive worked significantly better than tradi-
tional proton donors in these reactions and could be used at lower
concentrations. Given the unique reactivity displayed by SmI2–
DMAE, could this reagent system be used to reduce a range of sub-
strates? If so, does it function like the SmI2–water–amine system
developed by Hilmersson?
To address these questions, a series of substrates containing
representative functional groups were exposed to the SmI2–DMAE
system in THF as shown in Table 1. Interestingly, the reactions pro-
ceeded quickly and alkyl halides, a ketone, a model arene (anthra-
cene), and lactone (decanolide) were readily reduced in good to
excellent yields. A white precipitate formed in all reactions as they
progressed to completion. Characterization of the precipitate
revealed that it was the ammonium iodide salt of DMAE
(DMAE.HI+). A range of DMAE concentrations were explored, but
we found that in the substrates examined, addition of 5–6 equiv
of DMAE (relative to [SmI2]) was best. Lower concentrations of
DMAE led to slow or inefficient reductions. Large concentrations
of the additive (over 20 equiv) led to oxidation of SmI2 that likely
proceeded through reduction of DMAE providing a poor yield of
product.22 In one case, the addition of more DMAE led to a slight
increase in the time required for conversion to product, but impact
on yield was modest. In the case of anthracene, doubling the
amount of DMAE led to a decrease in the time for conversion
although the yield decreased slightly.
(D D
Hà) and entropy ( Sà) from the linear form of the Eyring equa-
tion. The data obtained from this set of experiments are displayed
in Table 3. The data show a small degree of bond reorganization
and a high degree of order in the activated complex.
Table 1
Reaction of representative substrates with DMAE in THF at 25 °C
Substrate
Product
equiv DMAE
Timec (min)
Yield (%)
relative to [SmI2]
1-Iodododecanea
1-Bromododecanea
1-Bromododecanea
Anthracenea
Dodecane
Dodecane
Dodecane
9,10-Dihydroanthracene
9,10-Dihydroanthracene
2-Heptanol
5
5
10
5
10
6
6
15
20
43
100
23
30
97 1d
83 1d
88 1d
99 1d
92 1d
99 1d
76e
Anthracenea
2-Heptanonea
5-Decanolideb
1,5-Decanediol
10
a
b
c
Conditions: 1 equiv substrate, 2.5 equiv SmI2.
Conditions: 1 equiv substrate, 7 equiv SmI2.
Time until solution decolorizes.
GC yields.
d
e
Isolated yield.