Communication
zation of the active ruthenium species. Evaluation of
both 5 and 7 by using cyclic voltammetry provided
a clear distinction between the two; where 5 was
inert, but 7 had an observable oxidation potential of
Table 2. Yield verification, and extended scope, facilitated by phenyl Grignard trap-
ping of crude aldehyde.
3.1 eV. More extensive studies involving cyclic vol-
tammetry, in combination with TPAP, are required for
further mechanistic understanding, and will be re-
ported in due course.
[
a]
[a]
Entry Diaryl Carbinol
Yield [%]
Entry Diaryl Carbinol
Yield [%]
In conclusion, a novel NMO complex (NMO·TPB, 7)
has been discovered, and applied to the Ley–Griffith
oxidation reaction. Utilising newly developed condi-
tions for 7, it was found that benzylic and allylic alco-
hols react with considerable selectivity over primary
and secondary alcohols, making this method amena-
ble to protecting group free oxidations in the case of
bi-functional diols (e.g., 10). A key feature of this
method is that the NMO·TPB (7) complex is non-hy-
groscopic and the oxidations can be run in non-anhy-
drous solvents open to the atmosphere. The scope of
NMO·TPB (7) is currently under investigation in other
NMO-based reactions to probe its wider applicability.
[
b]
[b]
1
82 (75)
4
82 (81)
[
b]
[b]
2
3
>95 (>95)
5
6
60 (59)
71
50
[
a] Overall yield based on a two-step reaction sequence (i.e., oxidation and phenyl
Grignard addition); [b] Isolated yield of intermediate aldehyde.
Only in the cases of benzyl- and 4-fluorobenzyl alcohol did
we observe trace amounts of carboxylic acid formation, 8a
and 9d (Table 1, entry 1 and Table 2, entry 4), in addition to
the aldehyde. However, these two arylaldehydes are well
known to undergo auto-oxidation to the corresponding car-
[
40]
boxylic acid.
Furthermore, in some cases involving non-
polar/volatile arylaldehydes, trace amounts of biphenyl were
detected as a minor by-product in this oxidation protocol,
which in these cases was difficult to remove by chromatogra-
phy or distillation. To verify the reported yields in these specific
cases 8a, b (Table 1, entries 1, 2), the reactions were repeated,
and crude aldehyde then trapped with phenyl magnesium bro-
mide, providing 9a, b (Table 2). Considering this analysis equa-
tes to a two-step reaction process, it demonstrates that the
yields of aryl aldehydes obtained above, 8a–b (Table 1, en-
tries 1, 2) are on the conservative side. This evaluation was ex-
tended to other difficult-to-handle aldehydes, affording the
corresponding diaryl carbinols 9c–f (Table 2, entries 3–6) in ac-
ceptable overall yields ranging from 50–82% yield for this two-
step process.
Scheme 3. Competition experiment using diol 10; (isolated yield);
[
BRMS=yield based on recovered starting material].
Experimental Section
Synthesis of NMO·TPB (7): NMO (5.00 g, 42.7 mmol) was dissolved
in a 1:1 mixture of ethanol (50 mL) and toluene (50 mL). Sodium
tetraphenylborate (7.30 mg, 21.3 mmol) was added, and the reac-
tion cooled in an ice/sodium chloride bath for 5 min before the ad-
dition of acetylacetone (7.85 mL, 76.4 mmol) drop-wise over 5 min.
The reaction was stirred for an additional 10 min, then filtered
cold, and the solid washed with toluene (20 mL). The resulting
white solid was air dried for 20 min, providing NMO·TPB (7) (8.95 g,
7
6%). The crude salt was dissolved in acetone/water (250 mL, 3:2)
then the solution was concentrated under reduced pressure below
08C (~160 Torr, ~100 mL removed) until crystallisation was initiat-
The fact that the NMO·TPB (7)/TPAP (3) reagent combination
was much less reactive towards aliphatic saturated primary
and secondary alcohol oxidation, but totally consumed aryl
and allylic alcohols, a competition experiment was undertaken
with bi-functional diol 10. Pleasingly, oxidation was highly se-
lective for the benzylic position (i.e., 11), with only slight oxida-
tion at the primary position (i.e., 12 and 13; Scheme 3). In
comparison, applying standard Ley–Griffith conditions to 10
yielded less of 11 (i.e., 60% yield BRSM), and more of 13 (25%
yield BRSM). The yield of compound 12 remained unchanged.
In terms of understanding the selectivity created by
NMO·TPB (7), as opposed to NMO (5), it is possible that
NMO·TPB (7) offers a substantial hydrophobic environment
due to the large TPB anion, and/or provides electronic stabili-
3
ed. The solution was then cooled in an ice bath for 1 h. The result-
ing white solid was filtered, washed with water (40 mL), air dried
for 10 min then dried under high vacuum for 1 h providing a white
crystalline product (7.85 g, 67%).
Representative NMO·TPB (7)/TPAP (3) oxidation protocol: Alco-
hol (1 mmol) was dissolved in HPLC grade acetonitrile (2.0 mL), fol-
lowed by addition of NMO·TPB (7; 416 mg, 0.75 mmol). After stir-
ring for 10 min at room temperature, TPAP (3; 17.6 mg, 5 mol%)
was added. The reaction was stirred at room temperature for 12–
1
6 h before quenching with water (8.0 mL). The solution was then
extracted with a mixture of pentane and diethyl ether (3:1, 3ꢁ
10 mL). The organic phases were combined, dried (Na SO ), and
4
4
the solvent removed by atmospheric distillation affording crude al-
Chem. Eur. J. 2015, 21, 1 – 6
3
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