Organic Letters
Letter
a
are limited to transition metal catalysis, requiring a higher
temperature (110−135 °C), an argon atmosphere, and often
long reaction times. Therefore, there is a strong interest in
designing an inexpensive, transition-metal-free system which
may operate under milder reaction conditions, possibly under
an aerobic atmosphere without generating hazardous waste.
Herein, we communicate a completely transition-metal-free
synthesis of vinyl nitriles which can tolerate both primary and
secondary alcohols as starting substrates and operates under
very mild reaction conditions. The reaction utilizes an ortho-
quinone, pyrenedione (PD), which functions under visible-
light-induced conditions and an aerobic atmosphere. The
dehydrogenating ability of PD relies on its ability to behave as
a two-electron shuttle from alcohol to O2. The overall
dehydrogenative coupling reaction operates in a single-pot
manner, at a mild reaction temperature of 60 °C. Use of such
an inexpensive catalyst under very mild recation conditions
demonstrates that the simple organic molecule such as PD
overcomes the current limitation of the transition metal, high
temperature, and elongated reaction time toward α-olefination
of nitriles.
Table 1. Screening of Optimal Reaction Conditions
entry catalyst loading
base
solvent
yield (%)
1
2
3
4
5
6
7
8
−
KOtBu (30 mol %)
KOtBu (15 mol %)
KOtBu (15 mol %)
KOtBu (20 mol %)
KOtBu (30 mol %)
KOH (30 mol %)
NaOH (30 mol %)
NaOtBu (30 mol %)
NEt3 (30 mol %)
Na2CO3 (30 mol %)
KOtBu (30 mol %)
KOtBu (30 mol %)
KOtBu (30 mol %)
−
Toluene
Toluene
Toluene
Toluene
Toluene
Toluene
Toluene
Toluene
Toluene
Toluene
DMSO
n.r.
10
33
64
80
5
10
53
n.r.
n.r.
n.r.
28
n.r.
n.r.
7
1 mol %
3 mol %
3 mol %
3 mol %
3 mol %
3 mol %
3 mol %
3 mol %
3 mol %
3 mol %
3 mol %
3 mol %
3 mol %
3 mol %
9
10
11
12
13
14
15
CH3CN
DMF
Toluene
Toluene
b
KOtBu (30 mol %)
a
Facile and reversible 2e−/2H+ redox processes between o-
benzoquinone and catechol are well-known.19 We have also
shown recently that predominantly ligand-based 2e−/2H+
redox involving the azo/hydrazo couple is very efficient in
conducting N-alkylation of amines, C3-alkylation of indoles,
and a few dehydrogenative coupling reactions.20−24 We
surmise that an extended and delocalized π-cloud may further
facilitate easy reduction of a dione to its monoreduced
semiquinonato form. This fact prompts us to choose PD as the
experimented molecule, where the pyrene core will likely allow
the added electron to delocalize, conferring extra stability to
the monoreduced form. Notably, a few quinone molecules
showed promise in dehydrogenation reactions mostly operated
under thermal conditions.25−28 Gratifyingly, a combination of
PD and a catalytic amount of base KOtBu, under photo-
induced conditions can provide convenient access to the target
vinyl nitriles at a fairly mild reaction temperature of 60 °C. The
use of benzyl alcohol and benzyl cyanide as the model
substrates resulted in an 80% yield of the desired 2,3-
diphenylacrylonitrile.
A series of optimization studies revealed that the best yield
can be obtained at only 3 mol % loading of PD, while a lower
loading of the catalyst decreases the yield considerably (Table
1, entry 2). The reaction offers optimum yields of products at 3
mol % loading of PD, 30 mol % loading of the base KOtBu,
and stirring the reaction mixture at 60 °C for 6 h under blue
LED (Table 1, entry 5).
While scanning the effect of bases (Table 1, entries 5−10), it
was observed that NaOH, KOH, NEt3, and Na2CO3 were
inefficient in performing the reaction. Although KOtBu proved
to be the most efficient base, affording product in 80% yield,
NaOtBu can also provide a moderate amount of product (entry
8). Optimization of the reaction medium proved toluene to be
very effective, whereas polar acetonitrile offered a poor yield
(Table 1, entry 12). In other polar solvents such as DMF and
DMSO (Table 1, entries 11, 13), the reaction does not
proceed. Appropriate control reactions disclose that the
reaction fails in the absence of PD, KOtBu, and visible light,
justifying the essential role of each component (Table 1,
entries 1, 14, 15). Although to fix the light source and to
quantify photochemical efficiency a blue LED strip (456 nm)
was used, the reaction can be easily carried out by exposing it
Reaction conditions: PD (x mol %), benzyl alcohol (1.2 mmol),
benzyl cyanide (1 mmol), base (y mol %), toluene (2 mL), 60 °C (oil
bath), 6 h under blue light (GC-MS yield). Reaction performed in
b
dark.
to any visible light source, such as a CFL lamp in the
laboratory or even sunlight.
With the optimized reaction conditions in hand, we
surveyed the generality of the reaction by investigating its
substrate scope (Table 2). When a variety of substituted benzyl
alcohols were chosen along with benzyl nitrile, the
corresponding vinyl nitriles (4a−4i) were obtained in very
good to excellent yields. Interestingly, p-substituted benzyl
alcohols with electron-donating −Et, −iPr (4f−4g) and
electron-withdrawing fluoro (4j) assembled the respective
vinyl nitriles in good yields (61−78%). Similarly, o- and p-
halide substitutions in benzyl alcohols were well tolerated
under the reaction conditions to furnish the product (4j−4n)
in moderate to very good yields (64−74%). Furthermore,
heterocyclic alcohols, such as furfuryl methanol and 2-pyridine
methanol, reacted with benzyl cyanide resulting in the product
4o−4p in 63−72% yield.
Encouragingly, the aliphatic alcohols also offered moderate
yields of the respective vinylated products. For example,
neopentyl alcohol was converted to the nitrile product (4q) in
59% yield. It is noteworthy that the oxidation of aliphatic
alcohols is often challenging, since these are considered as
unactivated alcohols due to the higher C−H bond strength.
Similarly, hexanol was converted to the respective vinylated
product (4r) in synthetically useful 38% yield. Notably,
dehydrogenative coupling of benzyl alcohol with 4-chloro-
phenyl acetonitrile and heteroaromatic 2-thiophene acetoni-
trile also afforded the corresponding vinyl nitriles in moderate
to good yields (4s−4t).
Finally, the dehydrogenative couplings of the more
challenging aliphatic nitriles were also performed which
resulted in 40−43% yields of products (4u−4v), albeit under
a slightly higher loading of base.
Next, we attempted to further expand the scope of the
reaction by considering secondary alcohols (Table 3) as
olefinating substrates. To our delight, a large array of secondary
alcohols responded very well and furnished the desired
2020
Org. Lett. 2021, 23, 2019−2023