P. Samunual, D. E. Bergbreiter / Tetrahedron Letters 57 (2016) 3272–3276
3273
O
ruthenate (TPAP) was used to form N,N-diethyl,N-methyl,N-poly-
isobutylammonium perruthenate 2 as shown in Figure 2. This
ion-exchange reaction was carried out in dichloromethane (DCM)
as a solvent. We presumed a 1:1 equilibrium mixture of 1 and 2
formed when the reaction was carried out with an equal amount
of TPAP and 1. The PIB-bound perruthenate 2 so formed was
expected to be phase selectively soluble in heptane versus a polar
solvent. This premise was easily tested visually because 2 is highly
colored. As shown in Figure 3, 2 is indeed phase selectively soluble
in heptane versus acetonitrile. This solubility contrasted with that
of TPAP which is phase selectively soluble in acetonitrile under the
same conditions.
To probe the utility of this heptane soluble TPAP analog as an
oxidizing agent, we explored oxidation of 1-phenylethanol to form
acetophenone. The PIB-bound perruthenate 2 was found to be
competent as an oxidation catalyst using NMO as the penultimate
oxidant as shown in Table 1. At room temperature in DCM in the
presence of molecular sieves, the reaction proceeded to 91% con-
version based on 1H NMR spectroscopy in 12 h. Oxidation of 1-phe-
nylethanol was also successful in heptane though it required
elevated temperature (80 °C) to effect a similar 93% conversion of
alcohol to ketone. In the first case, the DCM solvent was removed
under reduced pressure. The residue from that reaction was then
dissolved in heptane and that solution was extracted with acetoni-
trile to form an acetonitrile solution of the product ketone and a
heptane solution of 2. In the case of the reaction carried out in hep-
tane, the product was simply extracted with acetonitrile from a
heptane solution of 2. Recycling was then explored. However,
attempts to recycle the recovered heptane solution of 2 were only
modestly successful. A second cycle using the recovered 2 led to
only ca. 70% conversion of 1-phenylethanol to acetophenone. Sim-
ilar problems of diminished yields in recycling of polystyrene sup-
ported TPAP had been noted previously.9,21 In our experiments, we
also noted formation of traces of an insoluble material at the inter-
face of the heptane/acetonitrile phases in the biphasic product sep-
aration after an oxidation, leading us to believe that some
decomposition of 2 occurred.
O
O
O
O
O
OH
O
PS
OH
O
I
I
I
I
O
O
O
O
O
O
O
PS
cross-linked
polystyrene-bound
IBX
IBX
IBX-ester
Lee's cross-linked
polystyrene IBX
Figure 1. Analogs of IBX including polymer supported analogs.
and simple manner would be desirable. Prior studies have empha-
sized the use of a variety of insoluble supports for this purpose.14
These previous studies have reported the use of both inorganic
supports like silica gel15 and organic polymer supports like cross-
linked polystyrene.16,17 These studies that immobilized IBX oxi-
dants were precedented by earlier work by the Moss group who
also immobilized iodosobenzoate reagents on polystyrene. These
reagents are catalysts for phosphate ester hydrolyses and oxidize
readily oxidizable substrates.18 These insoluble polymer supported
oxidants facilitate workup and separation of spent oxidant and
product. In some cases recycling of the spent oxidant is also possi-
ble. Soluble polymer supported IBX oxidants too have been
reported. The Janda group also described the synthesis of soluble
polystyrene supported IBX analogs that were shown to be more
efficient at oxidizing alcohols than an analogous macroporous
insoluble polystyrene supported IBX.19 While these soluble oxi-
dants had some advantages and while they too could be separated
from products, the separation process involves solvent precipita-
tion and requires excess solvent.
The work here explores a different approach to immobilizing
and recycling TPAP and IBX oxidizing agents that use soluble poly-
mers. It relies on the phase selective solubility of PIB phase anchors
after an oxidation process to separate either of these oxidizing
agents from products using a liquid/liquid biphasic separation. As
we show below, it is straightforward to synthesize both perruthen-
ate oxidants and IBX ester oxidizing agents. We further show that
these soluble polymer bound perruthenate and IBX ester oxidants
are competent for alcohol oxidation and that they can be separated
easily from products. Although recycling the PIB bound perruthen-
ate catalyst was not completely successful, we were able to sepa-
rate spent PIB-bound IBX esters from products efficiently and
were also able to show that it is possible to both readily regenerate
and reuse this spent oxidant.
Pr4N RuO4
+
Pr4N
17
I
+
H
RuO4
H
DCM, rt
N
N
17
I
2
1
Figure 2. Synthesis of a PIB-bound tetraalkylammonium perruthenate oxidation
catalyst.
Results and discussion
Past work by the Bergbreiter group has shown that commer-
cially available alkene-terminated polyisobutylene oligomers with
Mn values from 1000 to 2300 Da can be converted into a variety of
ligands or catalysts with applications in organic synthesis.20 The
solubility that PIB groups confer on their reactive terminal func-
tionality allows these PIB bound species to both be nonpolar phase
anchored species in separations after reactions and highly soluble
catalysts for reactions with substrates that can be readily con-
ducted under homogeneous conditions. Inspired by these prior
examples, we have explored the potential for these same soluble
hydrocarbon oligomer supports as solubilizing and recycling han-
dles for two common oxidizing agents—catalytic tetraalkylammo-
nium perruthenate oxidants and stoichiometric hypervalent iodine
oxidants.
We initially examined PIB-bound perruthenate complexes as
potential recyclable catalytic oxidants. Using a series of established
transformations, alkene-terminated PIB was converted into a hep-
tane soluble PIB oligomer with a terminal tetraalkylammonium
iodide functional group.2 Then an ion exchange reaction of this
PIB-bound ammonium iodide with tetra-n-propylammonium per-
-
PIB-bound RuO4
heptane
MeCN
heptane
MeCN
versus
TPAP
Figure 3. Phase solubility of TPAP and PIB-bound perruthenate.
Table 1
Catalytic activity of PIB-bound tetraalkylammonium perruthenate in the oxidation of
1-phenylethanol to form acetophenone
Solvent
DCM
Time (h)
12
Temperature (°C)
Conversiona (%)
25
Cycle 1: 91
Cycle 2: 69
Heptane
12
80
Cycle 1: 93
Cycle 2: 73
The conversion of substrate to product was measured using 1H NMR
a
spectroscopy.