Aerobic C-H Functionalization Using Pyrenedione as the Photocatalyst

Article abstract of DOI:10.1055/s-0040-1707135

We disclose a visible-light-promoted aerobic alkylation of activated C(sp ³)-H bonds using pyrenedione (PYD) as the photocatalyst. Direct C-H bond alkylation of tetrahydrofuran with alkylidenemalononitriles is accomplished in over 90% yield in the presence of 5 mol% of PYD and 18 W blue LED light under ambient conditions. The substrate scope is extended to ethers, thioethers, and allylic C-H bonds in reactions with various electrophilic Michael acceptors. The catalytic turnover process is facilitated by oxygen. Our work represents the first example of using PYD as a photocatalyst to promote C(sp ³)-H alkylation, revealing the unique character of PYD as a novel organophotocatalyst.

Full text of DOI:10.1055/s-0040-1707135

SYNTHESIS
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© Georg Thieme Verlag Stuttgart · New York
2020, 52, A–I
feature
A
en
Y. Zhang et al.
Feature
Synthesis
Aerobic C–H Functionalization Using Pyrenedione as the
Photocatalyst
Yuannian Zhanga
a) hyperoxidation
Xin Yanga
Jie Wu*b
Dejiang Huang*a
O2
O
O
O
O
blue
light
H
PYD
OOH
a Department of Food Science and Technology, National
University of Singapore, Singapore, 117543, Singapore
fsthdj@nus.edu.sg
b) alkylation
O
CN
CN
b Department of Chemistry, National University of Singa-
pore, Singapore, 117543, Singapore
PYD
R
C
CN
CN
20 examples
44–94% yield
blue
light
H
C
chmjie@nus.edu.sg
C
PYD
R
Received: 27.03.2020
Accepted after revision: 05.05.2020
Published online: 02.06.2020
Eosin Y,9,10 acridinium salts11,12 and rhodamine deriva-
tives,13 which have been extensively applied in a wide vari-
ety of reactions mediated by visible light. Due to their low
cost, high absorption coefficients in the visible light region,
and long excited state lifetime, they might represent good
alternatives to transition-metal photocatalysts.
DOI: 10.1055/s-0040-1707135; Art ID: ss-2020-z0165-fa
Abstract We disclose a visible-light-promoted aerobic alkylation of ac-
tivated C(sp3)–H bonds using pyrenedione (PYD) as the photocatalyst.
Direct C–H bond alkylation of tetrahydrofuran with alkylidenemalono-
nitriles is accomplished in over 90% yield in the presence of 5 mol% of
PYD and 18 W blue LED light under ambient conditions. The substrate
scope is extended to ethers, thioethers, and allylic C–H bonds in reac-
tions with various electrophilic Michael acceptors. The catalytic turn-
over process is facilitated by oxygen. Our work represents the first ex-
ample of using PYD as a photocatalyst to promote C(sp3)–H alkylation,
revealing the unique character of PYD as a novel organophotocatalyst.
As a distinct class of photosensitizer, quinones occur
naturally and are well known stoichiometric oxidants. Their
potent hydrogen-abstracting and electron-accepting ability
makes them potentially excellent photocatalysts for the ac-
tivation of C–H bonds.14 For example, Fukuzumi et al. dis-
covered the photoredox catalytic conversion of benzene
into phenol with DDQ under visible light irradiation.15 Se-
lective fluorination of inactivated C–H bonds using anthra-
quinone (AQN) as the photocatalyst was reported by
Wong’s group.16 Recently, Arends disclosed an aerobic pho-
tocatalytic oxidation of alcohols with water-soluble sodium
AQN sulfonate under visible light irradiation.17 However,
there are still several limitations that exist with quinone
photocatalysts. Specifically, activation of AQN normally re-
quires irradiation with UV light due to its poor absorption
in the visible light region. The regeneration of DDQ in cata-
lytic cycles is problematic and thus requires a high catalyst
loading. Furthermore, the reaction scope applying AQN is
limited. Therefore, the development of robust quinone cata-
lysts with high catalytic performance, absorbing visible
light as well as activating substrates efficiently, is in high
demand.
Key words organophotocatalysts, pyrenedione, alkylation, tetra-
hydrofuran, visible light
Introduction
Direct functionalization of C(sp3)–H bonds using un-
functionalized inert precursors has attracted intense inter-
est in modern synthetic organic chemistry, thus greatly
simplifying synthetic routes.1–3 The development of visible-
light photocatalysts over the past decade has enabled many
novel methods for C(sp3)–H activation under mild condi-
tions that were previously impossible by other approach-
es.4,5 Currently, the most widely used visible-light photo-
catalysts are based on Ir and Ru transition-metal complex-
es, which combine excellent visible-light-harvesting
properties with rich redox chemistry due to metal-to-
ligand charge transfer excited states.6–8 However, their scar-
city, high cost and low recyclability has impeded the wide
application of transition-metal photocatalysts, especially
on large scale.
Pyrenediones (PYDs) are a class of aromatic quinones
with a pyrene backbone. Two isomers, namely 1,6-pyrene-
dione (1,6-PYD) and 1,8-pyrenedione (1,8-PYD), can be eas-
ily obtained on a large scale by the direct oxidation of
pyrene with K2Cr2O7.18 PYD exhibits strong absorption in
the visible light region.19 Moreover, PYD displays excellent
excited state oxidizing ability that is ideal for C–H activa-
tion.19 We have previously demonstrated that the generation
From an economic point of view, ideal photocatalysts
should be effective and robust, free of metal, and easily re-
cyclable. Examples of such metal-free photocatalysts are
© 2020. Thieme. All rights reserved. Synthesis 2020, 52, A–I
Georg Thieme Verlag KG, Rüdigerstraße 14, 70469 Stuttgart, Germany

B
Y. Zhang et al.
Feature
Synthesis
of H2O2 can be realized via a photocatalytic reaction be-
tween PYD and isopropanol, and its capability of in situ ox-
idizing organic compounds in a mild way.19 We herein dis-
close the photooxidation of a series of C–H partners, includ-
ing ethers and allylic compounds, by using 1,6-PYD as a
photocatalyst under visible light irradiation. The aerobic al-
kylation of these C–H partners with electron-deficient
alkenes has also been developed.
Results and Discussion
Design Strategy
Based on our preliminary findings, hydroperoxides
were generated from various -oxy and -allylic C–H sub-
strates with 1,6-PYD as the photocatalyst in the presence of
visible light irradiation and an ambient atmosphere. Be-
Biographical Sketches
Yuannian Zhang has just
completed her Ph.D. studies
(March 2020) at Professor Dejian
Huang’s lab at the National Uni-
versity of Singapore. Her
research is based on organo-
photocatalysis and the develop-
ment of fluorescent probes in
food analysis.
Xin Yang is a fourth year Ph.D.
student at Professor Dejian
Huang’s lab at the National Uni-
versity of Singapore. His re-
search involves the chemistry of
flavonoids.
Jie Wu obtained his Ph.D.
(organic chemistry) from Bos-
ton University and his research
interests include continuous
flow synthesis, photochemical
synthesis.
synthesis,
and
automated
Dejian Huang obtained his
Ph.D. (inorganic chemistry)
from Indiana University and his
research interests include catal-
ysis and the chemistry of bio-
active natural products.
© 2020. Thieme. All rights reserved. Synthesis 2020, 52, A–I

C
Y. Zhang et al.
Feature
Synthesis
cause of the high excited state oxidation potential of PYD
(E*red = + 2.28 V vs SCE, MeCN), we proposed that
ether/alkene radical cations were generated via visible-light
induced single-electron transfer (SET), followed by a
smooth deprotonation to form a transient -oxy/allylic rad-
ical species. Triplet oxygen (3O2) could subsequently react
with the -oxy/allylic radical to accomplish the hydroper-
oxidation (Table 1, entries 1–4). Considering the ease of ac-
cessing -oxy/allylic radicals upon irradiation in the pres-
ence of 1,6-PYD (Scheme 1, a), we envisioned that such rad-
icals would participate in C–C bond formation with Michael
acceptors, thereby furnishing direct alkylation of ether/
allylic C(sp3)–H bonds (Scheme 1, b).
PYD using tetrahydrofuran (THF) as the C–H donor and sol-
vent in the presence of an electron-deficient alkene and an
alkylidenemalononitrile (AMN) 1a, under air and an 18 W
blue LED light (Table 2). In order to enhance the reaction ef-
ficiency, heating was applied using a water bath at 50 °C.
Remarkably, 5 mol% of 1,6-PYD was able to catalyze this
transformation to afford a 94% isolated yield of alkylation
product 2a in 24 hours (entry 3). An excellent yield (92%)
was also obtained with 5 mol% of 1,8-PYD (entry 4). How-
ever, only a 28% yield was obtained in the absence of air,
demonstrating the requirement of oxygen for the catalytic
reaction (entry 6). This lower yield in the absence of oxygen
might be attributed to the residual oxygen in the reaction
system. To confirm that light and photocatalysts are indis-
pensable components of this reaction, control experiments
were conducted in the absence of either light or 1,6-PYD,
with no product being formed under these conditions (en-
tries 8 and 9). The performance of 1,6-PYD was also exam-
ined in acetone with 20 equivalents of THF, leading to, how-
ever, a relatively lower product yield of 50% (entry 2).
Therefore, the C–H partner was applied as both the solvent
and the reactant in subsequent experiments.
Table 1 1,6-PYD-Photocatalyzed Hydroperoxidation of -Oxy/Allylic
C(sp3)–H Bondsa
Entry
1
Substrate
Product
TON
110
O
O
OOH
OOH
O
O
2
90
O
O
O
O
Scope of C–H Substrates and Michael Acceptors
OOH
OOH
3
4
80
We then evaluated the scope of the C–H partners for
this convenient alkylation reaction using a catalytic amount
of 1,6-PYD and alkylidene 1a under visible-light irradiation.
160
a Reaction conditions: the ether or alkene (1 mL) was irradiated with 18 W
blue LED light in the presence of 1,6-PYD (2.32 mg, 0.01 mmol) under an
aerobic atmosphere. TON values were calculated based on analysis of the
1H NMR spectra of the crude product mixtures using 1,3,5-trimethoxy-
benzene as an internal standard.
Table 2 Optimization of the Reaction Conditionsa
O
CN
1,6-PYD
CN
a) hyperoxidation
O
+
CN
24 h, blue light
CN
O2
O
O
O
1a
2a
blue
light
H
PYD
OOH
Entry
Temp (°C)
PYD (mol%)
Atmosphere
Yield (%)b
b) alkylation
1
30
50
50
50
50
50
50
50
50
5
5
5
5
5
5
2
0
5
air
62
50
94
92
84
28
70
0
CN
CN
2c
3
air
O
R
O
H
air
air
O2
O
CN
CN
blue
light
PYD
4d
5
R
Scheme 1 Photocatalytic C–H functionalization by peroxidation or
alkylation
6
argon
air
7
8
air
Reaction Optimization
9e
air
0
To examine the feasibility of 1,6-PYD as a photocatalyst,
a model reaction, the alkylation of C–H bonds via radical
addition to an electron-deficient olefin, was selected. This
convenient transformation represents an atom- and step-
economical method for the formation of carbon–carbon
bonds. We initially attempted the reaction mediated by 1,6-
a Reaction conditions: 1a (0.2 mmol), 1,6-PYD, THF as the solvent (2 mL), 18
W blue LED strip.
b Yields were determined from the 1H NMR spectra of the crude product
mixture using 1,3,5-trimethoxybenzene as an internal standard.
c Reaction performed with THF (20 equiv) in acetone (2 mL).
d 1,8-PYD was used as the photocatalyst.
e Reaction performed without light.
© 2020. Thieme. All rights reserved. Synthesis 2020, 52, A–I

D
Y. Zhang et al.
Feature
Synthesis
To our delight, a wide range of C–H bonds was readily ac-
commodated. As depicted in Scheme 2, the use of ethers in-
cluding 1,4-dioxane, tetrahydropyran, 1,3-dioxolane, 2-
methyl-1,3-dioxolane and 3,3-dimethyloxetane gave the
corresponding alkylation products 2b–f in moderate to
good yields ranging from 44–75%. A thioether, tetrahydro-
thiophene, reacted smoothly to afford product 2g in 66%
yield. Moreover, functionalized allylic substrates, including
2,3-dimethylbut-2-ene and cyclohexene, produced the cou-
pling products 2h and 2i in moderate yields. Benzaldehyde
was also well tolerated and afforded direct alkylation prod-
uct 2j in 58% yield.
giving products 3i and 3j in good yields. However, other
Michael acceptors, including unsaturated aldehydes, ke-
tones and amides, were unreactive.
O
CN
CN
CN
CN
1,6-PYD (5 mol%), air
50 °C, 24 h, blue LED
+
R
O
R
yield (dr)
O
O
O
O
CN
CN
CN
CN
CN
CN
CN
CN
Cl
Br
C
CN
CN
CN
CN
1,6-PYD (5 mol%), air
50 °C, 24 h, blue LED
2a, 94% (1:1)
3a, 85% (1:1)
3b, 88% (1:1)
3c, 90% (1:1)
C
H
+
1a
yield (dr)
O
O
O
O
CN
CN
CN
CN
CN
CN
CN
O
CN
F3C
O2N
O2N
HO
O
O
O
O
O
O
O
CN
CN
CN
CN
CN
CN
CN
3e, 40%
3e', 40%
3d, 88% (1:1)
3f, 92% (1:1)
CN
CN
CN
2c, 70%
2b, 62% (1:1)
O
O
O
O
2e, 44% (1:1)
2a, 94% (1:1)
2d, 75%
CN
CN
CN
COOEt
CN
COOMe
CN
COOMe
O
S
O
CN
CN
CN
CN
CN
CN
CN
CN
3g, 93% (1:1)
3h, 50% (0.6:1) 3i, 78% (0.4:0.4:0.4:1)
3j, 61% (0.9:1)
CN
CN
Scheme 3 Reaction scope of the electron-deficient alkenes. Reagents
and conditions: alkene (0.2 mmol), 1,6-PYD (0.01 mmol, 5 mol%), THF
as the solvent (2 mL), 18 W blue LED strip, 50 °C, 24 h. Yields are of iso-
lated products. Diastereomeric ratios are based on analysis of the 1H
NMR spectrum of the crude reaction mixtures.
2f, 52% (1:1)
2g, 66% (1:1)
2h, 65%
2i, 60% (0.6:1)
2j, 58%
Scheme 2 Reaction scope of the C–H partners. Reagents and condi-
tions: 1a (0.2 mmol), 1,6-PYD (0.01 mmol, 5 mol%), C–H partner as sol-
vent (2 mL), 18 W blue LED strip, 50 °C, 24 h. Yields are of isolated
products. Diastereomeric ratios are based on analysis of the 1H NMR
spectrum of the crude reaction mixtures.
Mechanistic Studies
The proposed mechanism is depicted in Scheme 4. Upon
excitation by visible light, 1,6-PYD undergoes two sequen-
tial hydrogen atom abstractions from THF to deliver 1,6-PYDH2
II and a THF -oxy radical, which adds to the alkene to gen-
erate radical intermediate III. Triplet oxygen plays an essen-
tial role in the turnover step for regenerating 1,6-PYD, in
which hydrogen peroxide was produced, resulting in the
formation of 2a by donating a hydrogen atom. We also
questioned whether a hydrogen from the 1,6-PYDH2 inter-
mediate could be transferred directly to radical intermedi-
ate III.20 However, as previously outlined, only a 28% yield of
2a was generated in the absence of air (see Table 2), thus
eliminating this possibility.
Further examination of the generality of this alkylation
was evaluated with various AMN derivatives, demonstrat-
ing an extremely broad substrate scope (Scheme 3). A vari-
ety of electron-deficient and electron-rich aromatic rings
on the Michael acceptors, even with functional groups such
as phenols and aryl halides, participated in this coupling re-
action smoothly, affording moderate to excellent yields
(50–94%) of the expected products 3a–h in 24 hours. Re-
placement of the nitrile groups on the malononitrile moi-
ety with an ester, either one or two, was also applicable,
© 2020. Thieme. All rights reserved. Synthesis 2020, 52, A–I

E
Y. Zhang et al.
Feature
Synthesis
O
H2O2
O2
O
O
O
HO
CN
CN
O
O
H
2a
OH
II
HOO
H2O2
O
CN
CN
O
HO
HO
O
CN
O
H
CN
O
O
III
Scheme 4 Proposed photocatalytic mechanism for the alkylation
Several control experiments were conducted to gain in-
sights into the reaction mechanism. Firstly, no alkylation
product was obtained in the presence of radical scavengers
such TEMPO, suggesting that a radical process was involved
in the reaction. Secondly, the addition of the singlet oxygen
quencher NaN3 still afforded 2a with 60% yield, which
therefore excluded an energy-transfer pathway (see
Scheme S1, Supporting Information). Furthermore, a light
on/off experiment indicated that a radical chain reaction
was unlikely (Figure 1, a). The magnitude of the kinetic iso-
tope effect (KIE) given by kH/kD was 2.3, suggesting that hy-
drogen abstraction might be involved in the rate-limiting
step (Figure 1, b, Scheme S2). A deuterium labelling study
was also conducted to support the proposed catalytic
mechanism (Scheme S3).
Conclusions
In conclusion, we have disclosed 1,6-PYD as an organo-
photocatalyst for the visible-light-promoted aerobic alkyl-
ation of electron-deficient alkenes. Direct C(sp3)–H bond
functionalization of ethers, thioethers, and allylic com-
pounds with a wide variety of Michael acceptors has been
accomplished with good to excellent yields of the products
being obtained. The turnover process was facilitated by ox-
ygen. This mild and metal-free protocol reveals a promising
use of 1,6-PYD as a novel organophotocatalyst for C–H func-
tionalization under an aerobic environment.
Figure 1 (a) Time profile of the transformation with light on/off over
time. Reagents and conditions: 2a (0.2 mmol), 1,6-PYD (0.01 mmol, 5
mol%), THF as the solvent (2 mL), 18 W blue LED strip, 50 °C. Yields
were determined by analysis of the 1H NMR spectra of the crude reac-
tion mixtures. (b) Kinetic isotope effect experiments.
Bruker AVIII400 (400 MHZ) or Bruker AMX500 (500 MHz) spectrome-
ters. Chemical shifts were calibrated using residual undeuterated sol-
vent as an internal reference for 1H NMR (CHCl3: 7.26 ppm) and CDCl3
for 13C NMR (at 77.0 ppm). Multiplicities are indicated as follows: s
(singlet), d (doublet), t (triplet), q (quartet), m (multiplet), dd (doublet
of doublets), br s (broad singlet). High-resolution mass spectrometry
For general procedures on the PYD-catalyzed formation of hydroper-
oxides, see the supporting information. Chemicals and solvents were
purchased from commercial suppliers and used as received without
1
further purification. H NMR and 13C NMR spectra were recorded on
© 2020. Thieme. All rights reserved. Synthesis 2020, 52, A–I

F
Y. Zhang et al.
Feature
Synthesis
was performed using a Bruker microTOF-Q II 1026 mass spectrome-
ter. The blue LED strips (2 meters, 18 W) were purchased from InLEDs
Pte Ltd (Singapore). The NMR data for compounds 2a, 2b, 2c, 2e, 2f,
2g, 2h, 2i, 2j and 3h were in accordance with those reported in the
literature.20
HRMS-ESI: m/z [M – H]– calcd for C13H11N2O2: 227.0826; found:
227.0819.
2-[(2-Methyl-1,3-dioxolan-2-yl)(phenyl)methyl]malononitrile
(2d)
Yield: 36.4 mg (75%); colorless oil.
PYD-Catalyzed Alkylation; General Procedure
1H NMR (500 MHz, CDCl3):  = 7.59–7.47 (m, 2 H), 7.41 (dd, J = 5.0, 2.0
Hz, 3 H), 4.41 (d, J = 5.9 Hz, 1 H), 4.24–4.16 (m, 1 H), 4.18–4.09 (m, 2
H), 4.09–4.01 (m, 1 H), 3.50 (d, J = 5.8 Hz, 1 H), 1.14 (s, 3 H).
13C NMR (126 MHz, CDCl3):  = 133.80, 129.55, 129.22, 129.11,
112.73, 112.33, 109.23, 65.27, 63.88, 53.99, 24.39, 22.65.
Electron-deficient alkene 1 (0.2 mmol, 1.0 equiv) and 1,6-PYD (2.32
mg, 0.01 mmol, 5 mol%) were added to a 10 mL Pyrex tube equipped
with a magnetic stir bar. The corresponding C–H partner as the reac-
tant and solvent (2 mL) was added. Next, the reaction mixture was
placed under a blue LED (2 meter strips, 18 W) and irradiated at 50 °C
(water bath) for 24 h. The solvent was removed on a rotary evaporator
under reduced pressure and the residue was subjected to column
chromatography over silica gel by elution with hexane to hexane/eth-
yl acetate (10:1 to 2:1) to give the corresponding product.
HRMS-ESI: m/z [M – H]– calcd for C14H13N2O2: 241.0983; found:
241.0981.
2-[Phenyl(tetrahydro-2H-pyran-2-yl)methyl]malononitrile (2e)
Yield: 21.1 mg (44%); colorless oil; dr = 1:1.
2-[Phenyl(tetrahydrofuran-2-yl)methyl]malononitrile (2a)
1H NMR (500 MHz, CDCl3):  (mixture of two diastereomers) = 7.43–
7.31 (m, 10 H), 4.63 (d, J = 4.3 Hz, 1 H), 4.38 (d, J = 11.1 Hz, 1 H), 4.13–
4.04 (m, 2 H), 3.91–3.85 (m, 1 H), 3.76 (td, J = 10.7, 1.8 Hz, 1 H), 3.60–
3.49 (m, 1 H) 3.48 (td, J = 11.6, 2.9 Hz, 1 H), 3.20 (dd, J = 10.9, 3.6 Hz, 1
H), 3.09 (dd, J = 10.3, 4.3 Hz, 1 H), 1.85–1.73 (m, 2 H), 1.59–1.34 (m, 8
H), 1.20–1.05 (m, 1 H), 1.04–0.92 (m, 1 H).
13C NMR (126 MHz, CDCl3):  (mixture of two diastereomers) =
134.49, 134.09, 129.39, 129.27, 129.18, 128.82, 128.78, 128.60,
112.55, 112.45, 112.34, 111.95, 76.44, 76.14, 69.22, 68.98, 52.18,
51.64, 29.60, 29.08, 26.46, 26.15, 25.59, 25.58, 22.99, 22.90.
Yield: 42.4 mg (94%); colorless oil; dr = 1:1.
Compound 2a′
1H NMR (400 MHz, CDCl3):  = 7.45–7.35 (m, 8 H), 7.34–7.29 (m, 2 H),
4.54 (d, J = 4.1 Hz, 1 H), 4.46 (td, J = 7.1, 3.2 Hz, 1 H), 4.44–4.36 (m, 1
H), 4.39 (d, J = 10.7 Hz, 1 H), 4.00–3.92 (m, 1 H), 3.92–3.83 (m, 1 H),
3.75 (td, J = 6.4, 1.5 Hz, 2 H), 3.28 (dd, J = 10.6, 3.2 Hz, 1 H), 3.04 (dd,
J = 10.3, 4.2 Hz, 1 H), 2.03–1.92 (m, 1 H), 1.98–1.87 (m, 3 H), 1.86–1.73
(m, 1 H), 1.50–1.34 (m, 3 H).
13C NMR (101 MHz, CDCl3):  (mixture of two diastereomers) =
134.45, 133.97, 129.29, 129.26, 129.24, 128.99, 128.96, 128.52,
112.32, 112.30, 112.26, 111.70, 78.06, 77.49, 68.85, 68.74, 50.67,
52.05, 30.37, 28.90, 27.36, 27.01, 25.80, 25.80.
HRMS-ESI: m/z [M – H]– calcd for C14H13N2O: 225.1033; found:
225.1034.
HRMS-ESI: m/z [M – H]– calcd for C15H15N2O: 239.1190; found:
239.1197.
2-[(3,3-Dimethyloxetan-2-yl)(phenyl)methyl]malononitrile (2f)
Yield: 25.0 mg (52%); colorless oil; dr = 1:1.
1H NMR (500 MHz, CDCl3):  (mixture of two diastereomers) = 7.47–
7.34 (m, 10 H), 4.99 (d, J = 11.0 Hz, 1 H), 4.97 (d, J = 8.4 Hz, 1 H), 4.40
(d, J = 5.6 Hz, 1 H), 4.33 (d, J = 5.5 Hz, 1 H), 4.31 (d, J = 3.6 Hz, 1 H), 4.15
(d, J = 5.6 Hz, 1 H), 3.98 (d, J = 5.5 Hz, 1 H), 3.94 (d, J = 6.4 Hz, 1 H), 3.58
(dd, J = 11.2, 3.7 Hz, 1 H), 3.54 (dd, J = 8.6, 6.5 Hz, 1 H), 1.39 (s, 3 H),
1.28 (s, 3 H), 1.13 (s, 3 H), 0.97 (s, 3 H).
2-[(1,4-Dioxan-2-yl)(phenyl)methyl]malononitrile (2b)
Yield: 30.1 mg (62%); colorless oil; dr = 1:1.
1H NMR (400 MHz, CDCl3):  (mixture of two diastereomers) = 7.43
(d, J = 6.7 Hz, 3 H), 7.39–7.37 (m, 5 H), 7.34–7.31 (m, 2 H). 4.56 (d, J =
4.2 Hz, 1 H), 4.37 (d, J = 11.0 Hz, 1 H), 4.20–4.13 (m, 1 H), 4.10 (m, 1
H), 3.94–3.80 (m, 2 H), 3.88–3.80 (m, 2 H), 3.75 (dd, J = 11.8, 2.6 Hz, 1
H), 3.68 (dd, J = 11.8, 2.7 Hz, 1 H), 3.63–3.54 (m, 2 H), 3.51 (dd, J =
11.7, 2.5 Hz, 1 H), 3.44 (td, J = 11.7, 3.0 Hz, 1 H), 3.28 (dd, J = 11.0, 3.5
Hz, 1 H), 3.20 (dd, J = 11.7, 9.7 Hz, 1 H), 3.11 (dd, J = 10.8, 4.2 Hz, 1 H),
2.96 (dd, J = 11.6, 10.1 Hz, 1 H).
13C NMR (101 MHz, CDCl3):  (mixture of two diastereomers) =
133.37, 132.54, 129.74, 129.57, 129.24, 129.18, 129.01, 128.36,
111.98, 111.96, 111.84, 111.48, 73.80, 73.75, 69.30, 68.92, 67.71,
67.18, 66.22, 66.21, 48.46, 48.37, 26.15, 26.06.
13C
NMR
(126
MHz,
CDCl3):

(mixture
of
two
diastereomers) = 133.56, 132.37, 129.49, 129.32, 129.29, 129.27,
128.93, 128.63, 111.93, 111.34, 111.06, 111.03, 87.93, 87.13, 81.28,
80.77, 48.82, 47.48, 39.03, 38.40, 26.85, 26.70, 26.65, 25.97, 21.32,
21.22.
HRMS-ESI: m/z [M – H]– calcd for C15H15N2O: 239.1190; found:
239.1185.
2-[Phenyl(tetrahydrothiophen-2-yl)methyl]malononitrile (2g)
Yield: 31.9 mg (66%); colorless oil; dr = 1:1.
HRMS-ESI: m/z [M – H]– calcd for C14H13N2O2: 241.0983; found:
241.0980.
1H NMR (500 MHz, CDCl3):  (mixture of two diastereomers) = 7.54–
7.33 (m, 10 H), 4.60 (d, J = 4.3 Hz, 1 H), 4.22 (d, J = 6.1 Hz, 1 H), 4.15–
4.00 (m, 1 H), 4.02–3.87 (m, 1 H), 3.30 (dd, J = 9.2, 6.1 Hz, 1 H), 3.07–
2.93 (m, 3 H), 2.87–2.73 (m, 2 H), 2.37 (dt, J = 11.7, 5.6 Hz, 1 H), 2.09–
1.84 (m, 5 H), 1.74–1.58 (m, 2 H).
2-[(1,3-Dioxolan-2-yl)(phenyl)methyl]malononitrile (2c)
Yield: 31.9 mg (70%); colorless oil.
1H NMR (500 MHz, CDCl3):  = 7.52–7.37 (m, 5 H), 5.25 (d, J = 3.1 Hz, 1
H), 4.31 (d, J = 6.6 Hz, 1 H), 4.15–4.04 (m, 2 H), 4.07–3.86 (m, 2 H),
3.52 (dd, J = 6.6, 3.1 Hz, 1 H).
13C NMR (126 MHz, CDCl3):  (mixture of two diastereomers) =
136.18, 135.60, 129.31, 129.27, 129.25, 129.10, 128.31, 128.31,
112.00, 111.59, 111.50, 111.39, 53.87, 51.94, 50.26, 49.93, 35.71,
35.49, 33.13, 32.42, 31.10, 29.64, 29.61, 28.65.
13C NMR (126 MHz, CDCl3):  = 133.12, 129.26, 129.16, 128.91,
111.99, 111.76, 102.86, 65.87, 65.00, 49.24, 24.23.
© 2020. Thieme. All rights reserved. Synthesis 2020, 52, A–I

G
Y. Zhang et al.
Feature
Synthesis
HRMS-ESI: m/z [M – H]– calcd for C14H13N2S: 241.0805; found:
241.0798.
2-[(4-Bromophenyl)(tetrahydrofuran-2-yl)methyl]malononitrile
(3b)
Yield: 53.3 mg (88%); colorless oil; dr = 1:1.
2-(3,4-Dimethyl-1-phenylpent-3-en-1-yl)malononitrile (2h)
1H NMR (500 MHz, CDCl3):  (mixture of two diastereomers) = 7.58
(d, J = 8.4 Hz, 2 H), 7.54 (d, J = 8.3 Hz, 2 H), 7.29 (d, J = 8.5 Hz, 2 H), 7.23
(d, J = 8.4 Hz, 2 H), 4.57 (d, J = 4.1 Hz, 1 H), 4.45 (td, J = 7.4, 3.2 Hz, 1 H),
4.40–4.33 (m, 1 H), 4.36 (d, J = 10.6 Hz, 1 H), 3.97 (dt, J = 8.5, 6.5 Hz, 1
H), 3.89 (dt, J = 8.3, 6.7 Hz, 1 H), 3.77 (t, J = 6.8 Hz, 2 H), 3.29 (dd, J =
10.6, 3.2 Hz, 1 H), 3.04 (dd, J = 10.2, 4.1 Hz, 1 H), 2.07–1.84 (m, 4 H),
1.88–1.74 (m, 1 H), 1.55–1.40 (m, 2 H), 1.40–1.34 (m, 1 H).
13C NMR (126 MHz, CDCl3):  (mixture of two diastereomers) = 33.32,
132.93, 132.44, 132.15, 130.88, 130.09, 123.47, 123.23, 112.09,
112.02, 112.00, 111.43, 77.69, 77.22, 68.81, 68.75, 51.40, 49.98, 30.29,
28.85, 27.12, 26.89, 25.75, 25.74.
Yield: 30.9 mg (65%); colorless oil.
1H NMR (500 MHz, CDCl3):  = 7.59–7.30 (m, 5 H), 3.96 (d, J = 5.1 Hz, 1
H), 3.34 (ddd, J = 8.8, 6.8, 5.1 Hz, 1 H), 2.94 (dd, J = 14.0, 8.7 Hz, 1 H),
2.50 (dd, J = 14.0, 6.8 Hz, 1 H), 1.70 (s, 3 H), 1.66 (s, 3 H), 1.62 (s, 3 H).
13C NMR (101 MHz, CDCl3):  = 137.14, 130.03, 128.98, 128.77,
127.92, 122.56, 112.43, 111.91, 45.39, 37.26, 28.50, 20.97, 20.64,
18.30.
HRMS-ESI: m/z [M – H]– calcd for C16H17N2: 237.1397; found:
237.1400.
HRMS-ESI: m/z [M – H]– calcd for C14H12BrN2O: 303.0138; found:
303.0140.
2-[Cyclohex-2-en-1-yl(phenyl)methyl]malononitrile (2i)
Yield: 28.3 mg (60%); colorless oil; dr = 0.6:1.
1H NMR (500 MHz, CDCl3):  (mixture of two diastereomers) = 7.59–
7.33 (m, 10 H), 6.04–5.92 (m, 1 H), 5.85–5.68 (m, 2 H), 5.59–4.87 (m, 1
H), 4.26 (d, J = 5.0 Hz, 1 H), 4.19 (d, J = 4.7 Hz, 1 H), 3.06 (dd, J = 10.6,
4.9 Hz, 1 H), 3.00–2.85 (m, 2 H), 2.85–2.76 (m, 1 H), 2.09–1.95 (m, 5
H), 1.88–1.78 (m, 1 H), 1.76–1.49 (m, 4 H), 1.42–1.31 (m, 1 H), 1.31–
1.18 (m, 1 H).
13C NMR (101 MHz, CDCl3):  (mixture of two diastereomers) =
136.40, 136.31, 132.45, 130.16, 129.17, 128.89, 128.87, 128.52,
128.25, 126.34, 125.49, 112.15, 111.93, 111.79, 111.66, 51.34, 51.25,
37.06, 35.96, 27.71, 27.54, 27.46, 25.76, 25.11, 24.78, 21.18, 19.22.
2-[(Tetrahydrofuran-2-yl)(m-tolyl)methyl]malononitrile (3c)
Yield: 43.3 mg (90%); colorless oil; dr = 1:1.
1H NMR (500 MHz, CDCl3):  (mixture of two diastereomers) = 7.37–
7.25 (m, 2 H), 7.25–7.17 (m, 4 H), 7.13 (d, J = 7.2 Hz, 2 H), 4.55 (d, J =
4.1 Hz, 1 H), 4.48 (td, J = 7.2, 3.3 Hz, 1 H), 4.46–4.36 (m, 1 H), 4.40 (d,
J = 10.6 Hz, 1 H), 3.98 (dt, J = 8.5, 6.4 Hz, 1 H), 3.89 (dt, J = 8.5, 6.8 Hz, 1
H), 3.77 (t, J = 6.6 Hz, 2 H), 3.26 (dd, J = 10.6, 3.3 Hz, 1 H), 3.02 (dd, J =
10.3, 4.2 Hz, 1 H), 2.41 (s, 3 H), 2.39 (s, 3 H), 2.03–1.89 (m, 4 H), 1.86–
1.78 (m, 1 H), 1.54–1.39 (m, 3 H).
13C NMR (126 MHz, CDCl3):  (mixture of two diastereomers) =
138.94, 138.57, 134.38, 133.86, 129.95, 129.92, 129.64, 129.11,
129.05, 128.77, 126.09, 125.40, 112.36, 112.34, 112.33, 111.76, 78.08,
77.50, 68.80, 68.65, 51.83, 50.53, 30.29, 28.89, 27.29, 26.96, 25.80,
25.72, 21.41, 21.41.
HRMS-ESI: m/z [M + H]+ calcd for C16H17N2: 237.1386; found:
237.1382.
2-(2-Oxo-1,2-diphenylethyl)malononitrile (2j)
Yield: 30.2 mg (58%); colorless oil.
HRMS-ESI: m/z [M – H]– calcd for C15H15N2O: 239.1190; found:
239.1194.
1H NMR (500 MHz, CDCl3):  = 7.90 (d, J = 9.8 Hz, 2 H), 7.55 (t, J = 7.5
Hz, 1 H), 7.46–7.33 (m, 7 H), 5.10 (d, J = 8.5 Hz, 1 H), 4.54 (d, J = 8.4 Hz,
1 H).
2-{(Tetrahydrofuran-2-yl)[4-(trifluoromethyl)phenyl]methyl}-
malononitrile (3d)
13C NMR (126 MHz, CDCl3):  = 193.05, 134.33, 133.78, 131.99,
129.97, 129.79, 129.18, 128.87, 128.55, 112.10, 111.54, 54.64, 26.76.
HRMS-ESI: m/z [M + Na]+ calcd for C17H12N2NaO: 283.0842; found:
283.0852.
Yield: 51.7 mg (88%); colorless oil; dr = 1:1.
1H NMR (500 MHz, CDCl3):  (mixture of two diastereomers) = 7.70
(d, J = 8.1 Hz, 2 H), 7.66 (d, J = 8.1 Hz, 2 H), 7.53 (d, J = 8.1 Hz, 2 H), 7.47
(d, J = 8.1 Hz, 2 H), 4.59 (d, J = 4.2 Hz, 1 H), 4.46 (td, J = 7.5, 3.3 Hz, 1 H),
4.43–4.35 (m, 1 H), 4.40 (d, J = 10.4 Hz, 1 H), 4.01–3.92 (m, 1 H), 3.88
(dt, J = 8.5, 6.7 Hz, 1 H), 3.76 (t, J = 6.8 Hz, 2 H), 3.37 (dd, J = 10.6, 3.3
Hz, 1 H), 3.11 (dd, J = 10.2, 4.1 Hz, 1 H), 2.00–1.89 (m, 4 H), 1.88–1.79
(m, 1 H), 1.51–1.40 (m, 2 H), 1.33 (ddt, J = 12.4, 8.7, 7.6 Hz, 1 H).
13C NMR (126 MHz, CDCl3):  (mixture of two diastereomers) =
138.28, 138.02, 131.50 (q, J = 33.6 Hz), 131.23 (q, J = 33.4 Hz), 129.77,
129.05, 126.25 (q, J = 3.9 Hz), 125.92 (q, J = 3.6 Hz), 123.73 (q, J = 272.4
Hz), 123.68 (q, J = 272.1 Hz), 111.95, 111.86, 111.32, 77.65, 68.83,
68.82, 51.71, 50.25, 30.34, 28.91, 27.04, 26.89, 25.78, 25.75.
2-[(4-Chlorophenyl)(tetrahydrofuran-2-yl)methyl]malononitrile
(3a)
Yield: 44.2 mg (85%); colorless oil; dr = 1:1.
1H NMR (500 MHz, CDCl3):  (mixture of two diastereomers) = 7.43
(d, J = 8.5 Hz, 2 H), 7.39 (d, J = 8.5 Hz, 2 H), 7.35 (d, J = 8.5 Hz, 2 H), 7.30
(d, J = 8.7 Hz, 2 H), 4.57 (d, J = 4.1 Hz, 1 H), 4.46 (td, J = 7.4, 3.2 Hz, 1 H),
4.37 (d, J = 10.4 Hz, 1 H), 4.39–4.34 (m, 1 H), 3.97 (dt, J = 8.4, 6.5 Hz, 1
H), 3.89 (dt, J = 8.4, 6.7 Hz, 1 H), 3.77 (t, J = 6.9 Hz, 2 H), 3.30 (dd, J =
10.6, 3.2 Hz, 1 H), 3.05 (dd, J = 10.3, 4.1 Hz, 1 H), 2.07–1.89 (m, 4 H),
1.87–1.81 (m, 1 H), 1.55–1.43 (m, 2 H), 1.41–1.32 (m, 1 H).
HRMS-ESI: m/z [M – H]– calcd for C15H12F3N2O: 293.0907; found:
13C NMR (126 MHz, CDCl3):  (mixture of two diastereomers) =
135.26, 135.00, 132.82, 132.42, 130.58, 129.80, 129.47, 129.18,
112.11, 112.03, 112.03, 111.45, 77.26, 68.80, 68.74, 51.31, 49.89,
30.27, 28.84, 27.19, 26.96, 25.73, 25.73.
293.0912.
2-[(4-Nitrophenyl)(tetrahydrofuran-2-yl)methyl]malononitrile
(3e)
HRMS-ESI: m/z [M – H]– calcd for C14H12ClN2O: 259.0644; found:
Yield: 43.3 mg (80%); colorless oil; dr = 1:1.
259.0642.
© 2020. Thieme. All rights reserved. Synthesis 2020, 52, A–I

H
Y. Zhang et al.
Feature
Synthesis
Compound 3e
1H NMR (400 MHz, CDCl3):  (mixture of two diastereomers) = 7.56–
7.49 (m, 2 H), 7.47–7.31 (m, 8 H), 4.80 (s, 1 H), 4.67 (t, J = 7.3 Hz, 1 H),
4.28 (s, 1 H), 4.19 (t, J = 7.4 Hz, 1 H), 4.01–3.92 (m, 1 H), 3.92–3.83 (m,
1 H), 3.78–3.64 (m, 2 H), 1.99–1.70 (m, 5 H), 1.69 (s, 3 H), 1.58 (s, 3 H),
1.55–1.44 (m, 1 H), 1.37–1.27 (m, 1 H), 1.23–1.13 (m, 1 H).
1H NMR (500 MHz, CDCl3):  = 8.26 (d, J = 8.8 Hz, 2 H), 7.55 (d, J = 8.7
Hz, 2 H), 4.47 (td, J = 7.7, 3.3 Hz, 1 H), 4.41 (d, J = 10.5 Hz, 1 H), 3.77 (t,
J = 6.9 Hz, 2 H), 3.44 (dd, J = 10.5, 3.3 Hz, 1 H), 2.12–1.99 (m, 1 H),
1.94–1.79 (m, 1 H), 1.56–1.42 (m, 1 H), 1.34–1.25 (m, 1 H).
13C
NMR
(101
MHz,
CDCl3):

(mixture
of
two
13C NMR (126 MHz, CDCl3):  = 148.33, 141.20, 130.43, 124.08,
diastereomers) = 138.18, 136.69, 128.94, 128.68, 128.61, 128.44,
127.67, 126.63, 112.15, 112.14, 111.99, 82.56, 80.84, 69.46, 68.98,
48.25, 47.98, 34.37, 33.12, 27.26, 27.17, 26.28, 25.79, 19.44, 16.46.
HRMS-ESI: m/z [M + Na]+ calcd for C15H16N2NaO: 263.1155; found:
111,61, 111.56, 77.14, 68.88, 50.18, 28.98, 26.81, 26.75.
Compound 3e′
1H NMR (500 MHz, CDCl3):  = 8.30 (d, J = 8.7 Hz, 2 H), 7.60 (d, J = 8.7
Hz, 2 H), 4.62 (d, J = 4.2 Hz, 1 H), 4.40 (dt, J = 10.2, 6.8 Hz, 1 H), 3.97
(dt, J = 8.7, 6.6 Hz, 1 H), 3.89 (dt, J = 8.6, 6.7 Hz, 1 H), 3.18 (dd, J = 10.1,
4.2 Hz, 1 H), 2.08–1.91 (m, 3 H), 1.48–1.36 (m, 1 H).
263.1563.
Ethyl 2-Cyano-3-phenyl-3-(tetrahydrofuran-2-yl)propanoate (3i)
13C NMR (126 MHz, CDCl3):  = 148.48, 131.30, 129.70, 124.43,
Yield: 42.6 mg (78%); colorless oil; dr = 0.4:0.4:0.4:1.
1H NMR (500 MHz, CDCl3):  (mixture of four diastereomers) = 7.39–
7.27 (m, 20 H), 4.68-4.55 (m, 2 H), 4.56–4.46 (m, 2 H), 4.39 (m, 1 H),
4.31 (d, J = 5.2 Hz, 1 H), 4.28–4.17 (m, 4 H), 4.10–4.03 (m, 4 H), 4.01–
3.91 (m, 3 H), 3.89–3.80 (m, 4 H), 3.76–3.68 (m, 3 H), 3.43 (dd, J =
10.5, 3.2 Hz, 1 H), 3.39 (dd, J = 9.1, 5.4 Hz, 1 H), 3.31 (dd, J = 10.8, 3.3
Hz, 1 H), 3.24 (dd, J = 10.6, 5.2 Hz, 1 H), 1.95–1.82 (m, 12 H), 1.45–1.39
(m, 4 H), 1.29 (t, J = 7.1 Hz, 3 H), 1.21 (t, J = 7.1 Hz, 3 H), 1.08 (t, J = 7.1
Hz, 3 H). 0.97 (t, J = 7.1 Hz, 3 H).
111.74, 111.09, 77.51, 68.90, 51.65, 30.37, 26.90, 25.82.
HRMS-ESI: m/z [M – H]– calcd for C14H12N3O3: 270.0884; found:
270.0880.
2-[(4-Hydroxyphenyl)(tetrahydrofuran-2-yl)methyl]malononi-
trile (3f)
Yield: 44.5 mg (92%); colorless oil; dr = 1:1.
1H NMR (500 MHz, CDCl3):  (mixture of two diastereomers) = 7.21
(d, J = 8.6 Hz, 2 H), 7.15 (d, J = 8.6 Hz, 2 H), 6.84 (d, J = 8.5 Hz, 2 H), 6.81
(d, J = 8.6 Hz, 2 H), 4.52 (d, J = 4.1 Hz, 1 H), 4.41 (td, J = 7.1, 3.2 Hz, 1 H),
4.38–4.29 (m, 1 H), 4.35 (d, J = 10.7 Hz, 1 H), 4.00–3.90 (m, 1 H), 3.90–
3.80 (m, 1 H), 3.73 (td, J = 6.5, 1.7 Hz, 2 H), 3.21 (dd, J = 10.5, 3.2 Hz, 1
H), 2.97 (dd, J = 10.3, 4.1 Hz, 1 H), 1.96–1.83 (m, 5 H), 1.49–1.38 (m, 3
H).
13C NMR (126 MHz, CDCl3):  (mixture of two diastereomers) =
156.83, 156.59, 130.45, 129.68, 125.91, 125.32, 116.11, 115.87,
112.47, 112.43, 112.39, 111.82, 78.15, 77.60, 68.67, 67.66, 51.23,
49.90, 30.27, 28.86, 27.58, 27.18, 25.74, 25.69.
13C NMR (126 MHz, CDCl3):  (mixture of four diastereomers) =
165.67, 165.67, 165.59, 165.59, 136.19, 136.19, 135.56, 135.56,
129.69, 129.57, 129.25, 129.15, 129.01, 128.95, 128.77, 128.77,
128.62, 128.62, 128.27, 128.26, 128.21, 128.18, 128.15, 128.12, 79.23,
79.19, 79.00, 78.44, 68.62, 68.46, 68.42, 68.20, 62.83, 62.66, 62.43,
62.39, 51.18, 50.81, 50.21, 49.93, 42.99, 41.98, 41,47, 41.11, 30.36,
30.30, 29.45, 28.91, 25.82, 25.79, 25.74, 25.66, 13.88, 13.84, 13.79.
13.56.
HRMS-ESI: m/z [M + Na]+ calcd for C16H19NNaO3: 296.1257; found:
296.1255.
HRMS-ESI: m/z [M – H]– calcd for C14H13N2O2: 241.0983; found:
241.0975.
Dimethyl 2-[Phenyl(tetrahydrofuran-2-yl)methyl]malonate (3j)
Yield: 34.0 mg (61%); colorless oil; dr = 0.9:1.
1H NMR (500 MHz, CDCl3):  (mixture of two diastereomers) = 7.36–
7.09 (m, 10 H), 4.37–4.10 (m, 2 H), 4.22 (d, J = 11.7 Hz, 1 H), 3.92 (d, J =
10.1 Hz, 1 H), 3.80 (s, 3 H), 3.76 (s, 3 H), 3.84–3.70 (m, 2 H), 3.71–3.60
(m, 2 H), 3.54 (dd, J = 11.7, 2.9 Hz, 1 H), 3.47 (t, J = 10.1 Hz, 1 H), 3.40
(s, 3 H), 3.39 (s, 3 H), 2.01–1.77 (m, 4 H), 1.75–1.61 (m, 2 H), 1.57–
1.49 (m, 1 H), 1.47–1.37 (m, 1 H).
13C NMR (126 MHz, CDCl3):  (mixture of two diastereomers) =
168.89, 168.87, 168.33, 168.26, 138.55, 137.29, 129.84, 128.65,
128.39, 127.87, 127.23, 127.06, 81.86, 78.87, 68.53, 68.01, 56.33,
54.69, 52.61, 52.47, 52.15, 52.09, 51.46, 49.23, 30.25, 28.75, 25.69,
25.25.
2-[Naphthalen-2-yl(tetrahydrofuran-2-yl)methyl]malononitrile
(3g)
Yield: 51.3 mg (93%); colorless oil; dr = 1:1.
1H NMR (500 MHz, CDCl3):  (mixture of two diastereomers) = 8.11
(d, J = 8.6 Hz, 1 H), 8.03 (d, J = 8.6 Hz, 1 H), 8.00–7.86 (m, 4 H), 7.74 (d,
J = 7.3 Hz, 1 H), 7.67–7.46 (m, 7 H), 4.73–4.48 (m, 3 H), 4.41 (dd, J =
10.8, 3.4 Hz, 1 H), 4.20–4.11 (m, 2 H), 4.09 (dt, J = 8.6, 6.6 Hz, 1 H),
3.95 (dt, J = 8.6, 6.9 Hz, 1 H), 3.84–3.72 (m, 3 H), 2.04–1.85 (m, 4 H),
1.80–1.73 (m, 1 H), 1.46–1.36 (m, 1 H), 1.33–1.25 (m, 1 H).
13C NMR (126 MHz, CDCl3):  (mixture of two diastereomers) = 34.07,
133.87, 132.43, 131.81, 131.03, 130.02, 129.51, 129.41, 129.40,
129.37, 129.35, 127.10, 127.08, 126.18, 125.97, 125.36, 125.21,
125.10, 121.96, 121.80, 112.58, 112.31, 112.16, 112.14, 79.37, 77.67,
68.81, 68.71, 60.34, 44.18, 30.22, 28.84, 27.19, 26.92, 25.95, 25.75.
HRMS-ESI: m/z [M + Na]+ calcd for C16H20NaO5: 315.1203; found:
315.1198.
HRMS-ESI: m/z [M – H]– calcd for C18H15N2O: 275.1190; found:
275.1185.
Funding Information
Funding was provided by the National University of Singapore, the
Ministry of Education (MOE) of Singapore (MOE2014-T2-1-134,
MOE2017-T2-2-081) and the Natural Science Foundation of Jiangsu
2-[1-Phenyl-1-(tetrahydrofuran-2-yl)ethyl]malononitrile (3h)
Yield: 24.1 mg (50%); colorless oil; dr = 0.6:1.
Province, P. R. of China (BK20141219).
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© 2020. Thieme. All rights reserved. Synthesis 2020, 52, A–I

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Synthesis
Supporting Information
(10) Fan, X.; Xiao, P.; Jiao, Z.; Yang, T.; Dai, X.; Xu, W.; Tan, J. D.; Cui,
G.; Su, H.; Fang, W.; Wu, J. Angew. Chem. Int. Ed. 2019, 58, 12580.
(11) Capaldo, L.; Riccardi, R.; Ravelli, D.; Fagnoni, M. ACS Catal. 2018,
8, 304.
Supporting information for this article is available online at
https://doi.org/10.1055/s-0040-1707135.
S
u
p
p
orti
n
gInformati
o
n
S
u
p
p
orit
n
gInformati
o
n
(12) Wu, F. J.; Wang, L. F.; Chen, J. A.; Nicewicz, D. A.; Huang, Y.
Angew. Chem. Int. Ed. 2018, 57, 2174.
(13) Yu, Q.; Zhang, Y. T.; Wan, J. P. Green Chem. 2019, 21, 3436.
(14) Lerch, S.; Unkel, L. N.; Wienefeld, P.; Brasholz, M. Synlett 2014,
25, 2673.
(15) Ohkubo, K.; Fujimoto, A.; Fukuzumi, S. J. Am. Chem. Soc. 2013,
135, 5368.
(16) Kee, C. W.; Chin, K. F.; Wong, M. W.; Tan, C. H. Chem. Commun.
2014, 50, 8211.
(17) Zhang, W. Y.; Gacs, J.; Arends, I.; Hollmann, F. ChemCatChem
2017, 9, 3821.
(18) Yasutake, M.; Fujihara, T.; Nagasawa, A.; Moriya, K.; Hirose, T.
Eur. J. Org. Chem. 2008, 4120.
(19) Zhang, Y.; Yang, X.; Tang, H.; Liang, D.; Wu, J.; Huang, D. Green
Chem. 2020, 22, 22.
(20) Fan, X.-Z.; Rong, J.-W.; Wu, H.-L.; Zhou, Q.; Deng, H.-P.; Tan, J. D.;
Xue, C.-W.; Wu, L.-Z.; Tao, H.-R.; Wu, J. Angew. Chem. Int. Ed.
2018, 57, 8514.
References
(1) Choi, G. J.; Zhu, Q.; Miller, D. C.; Gu, C. J.; Knowles, R. R. Nature
2016, 539, 268.
(2) He, J.; Wasa, M.; Chan, K. S. L.; Shao, Q.; Yu, J.-Q. Chem. Rev.
2017, 117, 8754.
(3) Gandeepan, P.; Müller, T.; Zell, D.; Cera, G.; Warratz, S.;
Ackermann, L. Chem. Rev. 2019, 119, 2192.
(4) Marzo, L.; Pagire, S. K.; Reiser, O.; Konig, B. Angew. Chem. Int. Ed.
2018, 57, 10034.
(5) Xuan, J.; Xiao, W. J. Angew. Chem. Int. Ed. 2012, 51, 6828.
(6) Huo, H. H.; Shen, X. D.; Wang, C. Y.; Zhang, L. L.; Rose, P.; Chen,
L. A.; Harms, K.; Marsch, M.; Hilt, G.; Meggers, E. Nature 2014,
515, 100.
(7) Schultz, D. M.; Yoon, T. P. Science 2014, 343, 1239176.
(8) Twilton, J.; Le, C.; Zhang, P.; Shaw, M. H.; Evans, R. W.;
MacMillan, D. W. C. Nat. Rev. Chem. 2017, 1, 1.
(9) Srivastava, V.; Singh, P. P. RSC Adv. 2017, 7, 31377.
© 2020. Thieme. All rights reserved. Synthesis 2020, 52, A–I