Selective photochemical monoalkylation of active methylene compounds by alkenes. A green pathway for carbon-carbon bond formation

Article abstract of DOI:10.1016/j.jphotochem.2010.06.020

A novel photochemical method for selective α-monoalkylation of active methylene compounds has been developed. Aryl substituted alkenes and an aliphatic diene can be used as alkyl sources for these reactions, which proceed via polycyanoarene sensitized, photoinduced electron transfer pathways that are promoted using very mild conditions (ambient temperature, without noble metals and halogens, and with weak bases such as alkali metal carbonate). The reactions that comprise the new synthetic methods developed in this effort are both safe and environmentally friendly. Especially noteworthy is the fact that photochemical alkylation reactions of β-ketoesters (e.g., acetoacetic and malonic esters) can be used in the place of conventional strong base promoted processes.

Full text of DOI:10.1016/j.jphotochem.2010.06.020

Journal of Photochemistry and Photobiology A: Chemistry 214 (2010) 161–170
Contents lists available at ScienceDirect
Journal of Photochemistry and Photobiology A:
Chemistry
journal homepage: www.elsevier.com/locate/jphotochem
Selective photochemical monoalkylation of active methylene compounds by
alkenes. A green pathway for carbon–carbon bond formation
Maki Ohashi, Keisuke Nakatani, Hajime Maeda1, Kazuhiko Mizuno∗
Department of Applied Chemistry, Graduate School of Engineering, Osaka Prefecture University, 1-1 Gakuen-cho, Naka-ku, Sakai, Osaka 599-8531, Japan
a r t i c l e i n f o
a b s t r a c t
Article history:
A novel photochemical method for selective ␣-monoalkylation of active methylene compounds has been
developed. Aryl substituted alkenes and an aliphatic diene can be used as alkyl sources for these reac-
tions, which proceed via polycyanoarene sensitized, photoinduced electron transfer pathways that are
promoted using very mild conditions (ambient temperature, without noble metals and halogens, and
with weak bases such as alkali metal carbonate). The reactions that comprise the new synthetic methods
developed in this effort are both safe and environmentally friendly. Especially noteworthy is the fact that
photochemical alkylation reactions of ␤-ketoesters (e.g., acetoacetic and malonic esters) can be used in
the place of conventional strong base promoted processes.
Received 17 March 2010
Received in revised form 22 May 2010
Accepted 16 June 2010
Available online 23 June 2010
Keywords:
Photochemistry
Alkylation
© 2010 Elsevier B.V. All rights reserved.
C–C coupling
Electron transfer
Nucleophilic addition
1. Introduction
oligomerize (Scheme 1c) [8–10]. Highly efficient dimerization of
␤-dicarbonyl compounds via one-electron oxidation by cerium(IV)
Processes that directly transform carbon–hydrogen bonds into
carbon–carbon bonds are important synthetic methods [1–5].
However, from an ecological viewpoint [6,7], most of these reac-
tions are problematic owing to the fact that they rely on the use
of noble metal catalysts. Among various substrates explored for
these processes, active methylene compounds (1) including eno-
lizable ␤-dicarbonyl compounds are perhaps the most prominent
owing to the relatively high acidities of their methylene groups
[8–17]. Treatment of these substances with strong bases, such as
sodium hydride, results in formation of the corresponding anions,
which undergo C–C bond forming reactions with alkyl halides
via nucleophilic substitution (Scheme 1a) [18–21]. The use of ␤-
ketoesters in this fashion compriseswell-knownsynthetic methods
to obtain methyl ketones (acetoacetic ester synthesis) [11–13] and
carboxylic acids (malonic ester synthesis) [14–17].
ammonium nitrate (CAN) has been reported (Scheme 2) [22].
Methods have been explored to circumvent problems inherent
in base promoted alkylation reactions of ␤-dicarbonyl compounds
that are associated with the severe control of reaction condi-
tions [18] and indirect synthetic routes [23–27]. Recently, we have
explored a photochemical approach, aimed at solving the problems
seen with these reactions [28,29]. This effort led to the develop-
ment of a novel and facile method for direct ␣-monoalkylation
of propanedinitrile (1a, malononitrile) that occurs in the absence
of noble metal catalysts via photochemical polar addition (PPA)
[30–33] and photo-NOCAS (photochemical nucleophile–olefin
combination, aromatic substitution) [34–38] mechanistic path-
ways. The photoreaction proceeds efficiently under mild and
environmentally friendly conditions [28,29]. In further investiga-
tions in this area we have observed that the photochemical process
can be generally applied to ␣-monoalkylation reactions of a host of
active methylene compounds (1) (Schemes 3–5). The results of this
recent effort are described below.
The alkylation reactions, however, do not always afford the
desired products in high yields owing to the intervention of
side reactions. For example, over alkylation easily occurs to give
undesirable symmetrically disubstituted products (Scheme 1b)
[18]. Also, the anions of active methylene compounds tend to
2. Experimental
2.1. General
∗
Corresponding author. Tel.: +81 72 254 9289; fax: +81 72 254 9289.
E-mail address: mizuno@chem.osakafu-u.ac.jp (K. Mizuno).
Present address: Division of Material Sciences, Graduate School of Natural Sci-
Melting points were taken on YANACO MP-500 apparatus and
uncorrected. NMR spectra were recorded on Varian Mercury 300
spectrometer (300 and 75 MHz for 1H and 13C, respectively) using
tetramethylsilane as an internal standard. MS (EI+) were measured
1
ence and Technology, Kanazawa University, Kakuma-machi, Kanazawa, Ishikawa
920-1192, Japan.
1010-6030/$ – see front matter © 2010 Elsevier B.V. All rights reserved.
doi:10.1016/j.jphotochem.2010.06.020

162
M. Ohashi et al. / Journal of Photochemistry and Photobiology A: Chemistry 214 (2010) 161–170
Scheme 1. Conventional monoalkylation reactions of active methylene compounds (1). EWG represents electron-withdrawing group.
2.3. Typical procedure for PPA reactions (Table 1, entry 1)
To a Pyrex glass tube (1 cmØ) was added an acetonitrile
(4 mL)–water (1 mL) solution containing 1a (165 mg, 2.5 mmol), 2a
(13.5 mg, 75 ␮mol), 9-CP (5.1 mg, 25 ␮mol), and Li2CO3 (92.4 mg,
1.25 mmol). Argon gas was then bubbled through the solution for
5 min before it is sealed with a rubber septum and irradiated for
20 h using a 300-W high-pressure mercury lamp. The reaction mix-
ture was then neutralized by addition of aqueous HCl and extracted
with ether. The organic extracts were concentrated in vacuo giving
Scheme 2. Dimerization of acetylacetone via CAN oxidation.
a residue, which was subjected to 1H NMR analysis using CH2Br2 as
an internal standard to determine the yields of 3aa as 91%. Purifi-
by Shimadzu QP-5050 mass spectrometer with Shimadzu GC-17A
gas chromatograph. HRMS (EI+ and FAB+) were measured by JEOL
JMS-700 mass spectrometer. IR spectra were obtained from JASCO
FT/IR-230 spectrophotometer. Elemental analyses were carried out
on YANACO MT-6 or J-SCIENCE LAB JM-10 elemental analyzer.
X-ray crystallographic analyses were performed on Rigaku RAXIS-
RAPID diffractometer. Chiral gas–liquid chromatographic analyses
(chiral GC) were performed on Shimadzu GC-2014 gas chromato-
graph with SPELCO GAMMA DEX 225 column, and recorded on
Shimadzu C-R8A data processor. Preparative HPLCs were per-
formed by the use of JASCO Megapak GEL 201C column (GPC), JASCO
PU-986 pump, and Shodex RI-72 detector. Photoreactions were
conducted under irradiation of Eikohsha EHB-W-300 high-pressure
mercury lamp (300 W) through a Pyrex filter.
cation by silica gel chromatography (ethyl acetate after toluene)
followed by HPLC (GPC column, chloroform) gave pure 3aa as a
colourless solid.
2.4. Typical procedure for oxidative photodimerization reactions
(Table 3, entry 1)
To a Pyrex glass tube (1 cmØ) was added an acetonitrile
(4 mL)–water (1 mL) solution containing 1a (165 mg, 2.5 mmol), 4
(8.3 mg, 75 ␮mol), Li2CO3 (92.4 mg, 1.25 mmol), and 9-CP (5.1 mg,
25 ␮mol). Argon gas was bubbled through the solution for 5 min
before it is sealed with a rubber septum and irradiated for 20 h
using a 300-W high-pressure mercury lamp. The reaction mixture
was then neutralized by addition of aqueous HCl and extracted with
toluene–ether. The organic extracts were concentrated in vacuo
giving a residue (52% yield, determined by 1H NMR analysis using
CH2Br2 as an internal standard), which was subjected to column
chromatography on silica gel (ethyl acetate after toluene) to give a
crude product mixture. Further purification by HPLC (GPC column,
chloroform) gave 7a as a colourless solid.
2.2. Materials
Acetonitrile was distilled over CaH2 and then P2O5 before use.
Water was deionized by ion-exchange resin. Benzene was dis-
tilled over CaH2 and then over Na wire. 9-Cyanophenanthrene
(9-CP) and di-l-menthyl naphthalene-1,4-dicarboxylate (6) were
prepared by cyanation of 9-bromophenanthrene and esterification
of naphthalene-1,4-dicarboxylic acid, respectively. The other mate-
rials were purchased and used without further purification.
2.5. Typical procedure for three-component coupling reactions
(Table 4, entry 1)
To a Pyrex glass tube (1 cmØ) was added an acetonitrile
(4 mL)–water (1 mL) solution containing 1a (165 mg, 2.5 mmol),
4 (10.7 ␮L, 75 ␮mol), p-DCB (3.2 mg, 25 ␮mol), Phen (4.5 mg,
25 ␮mol), and Na2CO3 (132 mg, 1.25 mmol). Argon gas was bub-
bled through the solution for 5 min before it is sealed with a rubber
septum and irradiated for 20 h using a 300-W high-pressure mer-
cury lamp. The reaction mixture was then neutralized by addition
of aqueous HCl and extracted with toluene–ether. The organic
extracts were concentrated in vacuo giving a residue that contained
Scheme 3. Photochemical monoalkylation of 1 using PPA reaction.
Scheme 4. Photochemical monoalkylation of 1 using oxidative photodimerization reaction.

M. Ohashi et al. / Journal of Photochemistry and Photobiology A: Chemistry 214 (2010) 161–170
163
127.0 (2C), 127.9, 129.5 (2C), 142.2 ppm; MS (EI+) m/z = 184 (27,
M+), 118 (11), 105 (100, Ph(Me)CH+); HRMS (EI+) calcd for C12H12N2
184.1000, found 184.0974; IR (NaCl) ꢀ = 2255 (C N) cm−1
.
2-{2-[4-(1,1-Dimethylethyl)phenyl]ethyl}propanedinitrile
(3ah) [28]: pale yellow oil; 1H NMR (CDCl3, 300 MHz) ı = 1.36
(s, 9H), 2.34 (dt, J = 7.3, 7.3 Hz, 2H), 2.90 (t, J = 7.3 Hz, 2H), 3.56 (t,
J = 7.3 Hz, 1H), 7.12 (AAꢀXXꢀ, J = 8.5 Hz, 2H), 7.36 (AAꢀXXꢀ, J = 8.5 Hz,
2H) ppm; 13C NMR (CDCl3, 75 MHz) ı = 22.0, 31.8 (3C), 32.1, 33.0,
35.0, 112.7 (2C, –CN), 126.2 (2C), 128.3 (2C), 134.2, 150.5 ppm;
MS (EI+) m/z = 226 (10, M+), 211 (100, M+−Me); HRMS (EI+)
calcd for C15H18N2 226.1470, found 226.1448; IR (NaCl) ꢀ = 2218
(C N) cm−1
.
Dimethyl 2-(2,2-diphenylethyl)malonate (3ba): pale yellow
oil; 1H NMR (CDCl3, 300 MHz) ı = 2.67 (dd, J = 8.1, 7.4 Hz, 2H,
–CH2–), 3.28 (t, J = 7.4 Hz, 1H, –CH(CO2Me)2), 3.94 (t, J = 8.1 Hz,
1H, –CHPh2), 7.15–7.31 (m, 10H, aromatic) ppm; 13C NMR (CDCl3,
75 MHz) ı = 34.7, 48.9, 50.2, 52.8 (2C, –CO2Me), 126.5 (2C), 127.8
(4C), 128.6 (4C), 143.0 (2C), 169.5 (2C, C O) ppm; MS (EI+)
m/z = 312 (2, M+), 180 (100), 167 (23, Ph2CH+); IR (NaCl) ꢀ = 1736
Scheme 5. Photochemical monoalkylation of 1 using photo-NOCAS reaction.
87% and 25% yield of p-5a (based on the amount of p-DCB used) and
7a (based on the amount of 4 used), respectively, as determined by
1H NMR using CH2Br2 as an internal standard. Column chromatog-
raphy on silica gel (ethyl acetate after toluene) gave a crude product
mixture, which was purified by HPLC (GPC column, chloroform) to
yield pure p-5a and 7a as colourless oils.
(C O) cm−1
.
Dimethyl 2-(2-phenylethyl)malonate (3bf) [42]: colourless
oil; 1H NMR (300 MHz, CDCl3) ı = 2.23 (td, J = 7.7, 7.5 Hz, 2H,
–CH2–), 2.65 (t, J = 7.7 Hz, 2H, –CH2Ph), 3.38 (t, J = 7.5 Hz, 1H,
–CH(CO2Me)2), 3.73 (s, 6H, –CO2Me), 7.14–7.23 (m, 3H, aro-
matic), 7.23–7.32 (m, 2H, aromatic) ppm; 13C NMR (75 MHz,
CDCl3) ı = 30.9 (2◦), 33.8 (–CHPh2), 51.3 (–CH(CO2Me)2), 53.0 (2C,
–CO2Me), 126.4, 128.6 (2C), 128.7 (2C), 140.6 (ipso), 169.8 (2C,
2.6. Spectral data of photoproducts
2-(2,2-Diphenylethyl)propanedinitrile (3aa) [28,39]: colour-
less blocks, mp 92–94 ◦C, 1H NMR (CDCl3, 300 MHz) ı = 2.76 (dd,
J = 8.1, 8.1 Hz, 2H), 3.44 (t, J = 8.1 Hz, 1H), 4.22 (t, J = 8.1 Hz, 1H),
7.22–7.43 (m, 10H) ppm; 13C NMR (CDCl3, 75 MHz) ı = 21.8, 37.0,
48.4, 112.5 (2C, CN), 127.7 (4C), 127.8 (2C), 129.4 (4C), 140.7 (2C,
ipso) ppm; MS (EI+) m/z = 246 (18, M+), 168 (15), 167 (100, Ph2CH+),
165 (10); HRMS (EI+) calcd for C17H14N2 246.1157, found 246.1165;
C
O) ppm.
Dimethyl 2-(2-phenylpropyl)malonate (3bg) [43]: pale yel-
low oil; 1H NMR (300 MHz, CDCl3) ı = 1.28 (dd, J = 7.0, 0.4 Hz,
3H, –CHMePh), 2.10–2.30 (m, 2H, –CH2–), 2.64–2.78 (m, 1H,
–CHMePh), 3.21 (dd, J = 8.9, 6.2 Hz, 1H, –CH(CO2Me)2), 3.63 (s,
3H, –CO2Me), 3.74 (s, 3H, –CO2Me), 7.13–7.23 (m, 3H, aromatic),
7.25–7.33 (m, 2H, aromatic) ppm; 13C NMR (75 MHz, CDCl3) ı = 23.0
(–CHMePh), 37.5 (–CH2–), 38.4 (–CHMePh), 50.5 (–CH(CO2Me)2),
52.8 (2C, –CO2Me), 126.6, 127.2 (2C), 128.7 (2C), 145.3 (ipso),
169.77 (–CO2Me), 169.85 (–CO2Me) ppm; MS (EI+) m/z = 250 (3,
M+), 132 (91, CH2(CO2Me)2•+), 118 (100, PhCHMe = CH2•+), 105
(51, PhC+HMe); IR (NaCl) ꢀ = 702, 1154, 1237, 1436, 1739 (C O),
IR (NaCl) 703, 1451, 1496, 2255 (m, C N), 2900, 3029 cm−1
.
2-(1-Methyl-2,2-diphenylethyl)propanedinitrile (3ab) [28]:
pale yellow oil; 1H NMR (CDCl3, 300 MHz) ı = 1.30 (d, J = 6.7 Hz,
3H), 2.97–3.04 (m, 1H), 3.64 (d, J = 3.4 Hz, 1H), 3.80 (d, J = 11.8 Hz,
1H), 7.21–7.37 (m, 10H) ppm; 13C NMR (CDCl3, 75 MHz) ı = 16.1,
28.5, 40.4, 56.4, 111.0 (–CN), 113.0 (–CN), 127.5 (2C + 1C), 127.8
(2C), 128.1, 129.2 (2C), 129.8 (2C), 140.7, 140.8 ppm; MS (EI+)
m/z = 260 (4, M+), 167 (100, Ph2CH+); HRMS (EI+) calcd for C18H16N2
2956 cm−1
.
Ethyl 2-(2,2-diphenylethyl)-3-oxobutyrate (3ca): colourless
oil; 1H NMR (CDCl3, 300 MHz) ı = 1.26 (t, J = 7.1 Hz, 3H, –OCH2Me),
2.15 (s, 3H, –Ac), 2.55–2.71 (m, 2H, –CH2–), 3.36 (dd, J = 7.1,
7.1 Hz, 1H, –CH(Ac)CO2Et), 3.94 (dd, J = 8.1, 8.1 Hz, 1H, –CHPh2),
4.17 (q, J = 7.1 Hz, 2H, –OCH2Me), 7.15–7.38 (m, 10H) ppm; 13C
NMR (75 MHz, CDCl3): ı = 14.7 (–OCH2Me), 29.8 (–C( O)Me), 34.1
(–CH2–), 49.2 (–CHPh2), 58.2 (–CH(Ac)CO2Et), 61.9 (–OCH2Me),
126.7, 126.8, 128.0 (2C), 128.1 (2C), 128.7 (2C), 128.8 (2C), 143.56
(ipso), 143.62 (ipso), 169.6 (–CO2Et), 202.7 (–C( O)Me) ppm; MS
(EI+) m/z = 292 (1), 265 (1, M+−OEt), 180 (100, Ph2C CH2•+), 167
(16, Ph2CH+), 165 (38); IR (NaCl) ꢀ = 702, 1718 (C O), 1736 (C O),
260.1313, found 260.1290; IR (NaCl) ꢀ = 2253 (C N) cm−1
.
2-(1-Ethyl-2,2-diphenylethyl)propanedinitrile (3ac): MS
(EI+) m/z = 274 (3, M+), 167 (100, Ph2CH+), 165 (18), 152 (12).
2-[2,2-Bis(4-methoxyphenyl)ethyl]propanedinitrile
(3ae)
[28]: pale yellow oil; 1H NMR (CDCl3, 300 MHz) ı = 2.67 (dd, J = 8.3,
8.0 Hz, 2H), 3.44 (t, J = 8.0 Hz, 1H), 3.77 (s, 6H), 4.11 (d, J = 8.3 Hz,
1H), 6.86 (AAꢀXXꢀ, J = 8.8 Hz, 4H), 7.13 (AAꢀXXꢀ, J = 8.8 Hz, 4H) ppm;
13C NMR (CDCl3, 75 MHz) ı = 21.8, 37.4, 46.9, 55.7 (2C), 112.7 (2C,
–CN), 114.8 (4C), 128.6 (4C), 133.2 (2C), 158.9 (2C) ppm; MS (EI+)
m/z = 306 (17, M+), 240 (1, M+−CH2(CN)2), 228 (18), 227 (100,
(MeOC6H4)2CH+); HRMS (EI+) calcd for C19H18N2O2 306.1368,
found 306.1378; IR (NaCl) ꢀ = 579, 833, 1033, 1179, 1249 (C–O–C),
2981 (C N) cm−1
.
Ethyl 2-cyano-4,4-diphenylbutyrate (3da): pale yellow oil;
1H NMR (CDCl3, 300 MHz) ı = 1.28 (t, J = 7.1 Hz, 3H, –OCH2Me),
2.53–2.62 (m, 1H, –CH2–), 2.72–2.81 (m, 1H, –CH2–), 3.29
(dd, J = 10.0, 5.5 Hz, 1H, –CH(CN)CO2Et), 4.19 (q, 2H, J = 7.1 Hz,
–OCH2Me), 4.19–4.25 (m, 1H, –CHPh2), 7.18–7.35 (m, 10H, aro-
matic) ppm; 13C NMR (CDCl3, 75 MHz) ı = 14.1, 35.4, 36.3, 48.4, 62.9
(–OCH2Me), 116.1, 126.7, 127.0, 127.3 (2C), 127.6 (2C), 128.5 (2C),
128.8 (2C), 141.2, 142.3, 165.5 (C O) ppm; MS (EI+) m/z = 293 (6,
M+), 180 (100, Ph2C CH2•+), 167 (29, Ph2CH+); IR (NaCl) ꢀ = 2249
1509, 1609, 2255 (m, C N), 2838, 2905 cm−1
.
2-(2-Phenylethyl)propanedinitrile (3af) [28,40,41]: pale yel-
low powder, mp 42–43 ◦C; 1H NMR (CDCl3, 300 MHz) ı = 2.35 (dt,
J = 7.3, 7.3 Hz, 2H), 2.94 (t, J = 7.3 Hz, 2H), 3.57 (t, J = 7.3 Hz, 1H),
7.18–7.38 (m, 5H) ppm; 13C NMR (CDCl3, 75 MHz) ı = 22.1, 32.7,
33.0, 112.6 (2C, –CN), 127.5, 128.6 (2C), 129.3 (2C), 137.4 ppm;
MS (EI+) m/z = 170 (36, M+), 91 (100, PhCH2+); IR (NaCl) ꢀ = 2257
(C N) cm−1
.
(C N) cm−1
.
2-(2-Phenylpropyl)propanedinitrile (3ag) [28]: colourless oil;
1H NMR (CDCl3, 300 MHz) ı = 1.38 (d, J = 6.9 Hz, 3H), 2.15–2.42 (m,
2H), 3.00–3.05 (m, 1H), 3.20–3.33 (m, 1H), 7.19–7.39 (m, 10H) ppm;
13C NMR (CDCl3, 75 MHz) ı = 21.6, 22.4, 38.0, 39.4, 112.5 (2C, –CN),
Ethyl 2-cyano-3-methyl-4,4-diphenylbutyrate (3db): mixture
(86:14) of diastereomers, pale yellow oil; 1H NMR (300 MHz,
CDCl3) ı = 1.03 (d, J = 6.6 Hz, 3H, –CHMe–, major isomer), 1.12
(d, J = 6.7 Hz, 3H, –CHMe–, minor isomer), 1.31 (t, J = 7.1 Hz, 3H,

164
M. Ohashi et al. / Journal of Photochemistry and Photobiology A: Chemistry 214 (2010) 161–170
–CH2Me), 3.10–3.24 (m, 1H, –CHMe–), 3.49 (d, J = 3.0 Hz, 1H,
–CH(CN)CO2Et, major isomer), 3.54 (d, J = 3 Hz, 1H, –CH(CN)CO2Et,
minor isomer), 3.83 (d, J = 12.1 Hz, 1H, –CHPh2, major isomer), 4.08
(d, J = 12 Hz, 1H, –CHPh2, minor isomer), 4.26 (q, J = 7.1 Hz, 2H,
–CO2CH2Me), 7.12–7.42 (m, 10H) ppm; MS (EI+) m/z = 307 (0.4, M+),
194 (65, Ph2C CHMe•+), 167 (100, Ph2CH+). HRMS (FAB+) calcd for
C20H22NO2 ([M+H]+) 308.1651, found 308.1616.
CDCl3) ı = 1.25 (s, 6H, –Me), 1.38 (s, 6H, –Me), 3.38 (s, 1H,
–CH(CO2Me)2), 3.70 (s, 6H, –CO2Me), 5.56 (d, J = 16.0 Hz, 1H, olefin),
5.69 (d, J = 16.0 Hz, 1H, olefin), 7.39 (dd, J = 7.8, 7.7 Hz, 1H, 5-
position), 7.47 (ddd, J = 7.7, 1.4, 1.4 Hz, 1H), 7.56 (ddd, J = 7.8,
1.4, 1.4 Hz, 1H), 7.61 (dd, J = 1.4, 1.4 Hz, 1H, 2-position) ppm;
13C NMR (75 MHz, CDCl3) ı = 26.3 (2C, –Me), 29.2 (2C, –Me),
38.6 (4◦), 40.8 (4◦), 52.4 (2C, –CO2Me), 61.3 (–CH(CO2Me)2),
112.3 (4◦), 119.4 (–CN), 129.0, 129.6, 130.2, 131.0, 134.2,
136.5, 150.7 (ipso), 168.2 (2C, –CO2Me) ppm; MS (EI+) m/z = 343
(8, M+), 212 (47, M+−CH(CO2Me)2), 196 (43), 173 (47), 170
(100, NC–C6H4–CMe2CH CH+), 141 (44); HRMS (EI+) calcd for
C20H25NO4 343.1784, found 343.1781; IR (NaCl) ꢀ = 1145, 1243,
2-(2,2-Diphenylethyl)-2-methylpropanedinitrile (3ha): pale
yellow powder, mp 96–97 ◦C; 1H NMR (CDCl3, 300 MHz) ı = 1.67
(s, 3H, –Me), 2.64 (d, J = 7.5 Hz, 2H, –CH2–), 4.28 (t, J = 7.5 Hz, 1H,
–CHPh2), 7.16–7.29 (m, 10H, aromatic) ppm; 13C NMR (CDCl3,
75 MHz) ı = 26.7 (–Me), 31.2 (–CMe(CN)2), 44.3 (–CH2–), 48.9
(–CHPh2), 115.5 (2C, –CN), 127.4, 127.7, 128.9, 141.7 ppm; MS
(EI+) m/z = 260 (14, M+), 167 (100, Ph2CH+); IR (NaCl) ꢀ = 2248
1735 (C O), 2228 (C N), 2964 cm−1
.
Ethyl 2-acetyl-6-(4-cyanophenyl)-3,3,6-trimethylhept-4-en
oate (p-5c): 1H NMR (300 MHz, CDCl3) ı = 1.21 (s, 3H, –Me), 1.22
(s, 3H, –Me), 1.26 (t, J = 7.3 Hz, 3H, –CO2CH2Me), 1.39 (s, 6H, –Me),
2.19 (s, 3H, –Ac), 3.43 (s, 1H, –CH(Ac)CO2Et), 4.15 (q, J = 7.3 Hz, 2H,
–CO2CH2Me), 5.55 (d, J = 16.1 Hz, 1H, olefin), 5.71 (d, J = 16.1 Hz,
1H, olefin), 7.43 (AAꢀXXꢀ, J = 8.2 Hz, 2H, aromatic), 7.58 (AAꢀXXꢀ,
J = 8.2 Hz, 2H, aromatic) ppm; 13C NMR (75 MHz, CDCl3) ı = 14.7
(–CO2CH2Me), 26.4 (–Me), 26.6 (–Me), 29.0 (–Me), 29.1 (–Me),
31.8, 39.0, 41.2, 61.3 (–CO2CH2Me), 68.7 (–CH(Ac)CO2Et), 109.9
(4◦), 119.2 (–CN), 127.2 (2C), 132.0 (2C), 132.0 (olefin), 134.4
(olefin), 136.2 (olefin), 154.7 (ipso), 168.6 (2C, –CO2Et), 202.2
(–C( O)Me) ppm; MS (EI+) m/z = 341 (0.5, M+), 196 (14), 170 (20,
NC–C6H4–CMe2CH CH+), 129 (16, +CH(Ac)CO2Et), 116 (11), 43
(100, Ac+); IR (NaCl) ꢀ = 1145, 1365, 1717 (C O), 2227 (C N),
(C N) cm−1
.
2-[trans-4-(4-Cyanophenyl)-1,1,4-trimethylpent-2-
enyl]propanedinitrile (p-5a) [29]: colourless oil, 1H NMR
(CDCl3, 300 MHz) ı = 1.39 (s, 6H), 1.44 (s, 6H), 3.56 (s, 1H), 5.50 (d,
J = 15.9 Hz, 1H), 5.87 (d, J = 15.9 Hz, 1H), 7.42 (AAꢀXXꢀ, J = 8.7 Hz, 2H),
7.60 (AAꢀXXꢀ, J = 8.7 Hz, 2H) ppm; 13C NMR (CDCl3, 75 MHz) ı = 25.6
(2C), 28.9 (2C), 36.1, 40.6, 41.6, 110.3, 111.9 (2C), 119.1, 127.2 (2C),
129.6, 132.3 (2C), 141.4, 153.3 ppm; MS (EI+) m/z = 277 (4, M+), 212
(18, M+−CH(CN)2), 182 (14), 170 (100, M+−CMe2CH(CN)2), 156
(18); HRMS (EI+) calcd for C18H19N3 277.1579, found 277.1572; IR
(NaCl) 840, 2228 (C N), 2252 (w, C N), 2972 cm−1
.
2-[trans-4-(2-Cyanophenyl)-1,1,4-trimethylpent-2-
enyl]propanedinitrile (o-5a) [29]: pale brown oil; 1H NMR
(CDCl3, 300 MHz) ı = 1.40 (s, 6H), 1.58 (s, 6H), 3.66 (s, 1H), 5.49 (d,
J = 15.9 Hz, 1H), 5.94 (d, J = 15.9 Hz, 1H), 7.32 (ddd, J = 7, 7, 2 Hz, 1H),
7.50–7.60 (m, 2H), 7.66 (dd, J = 7, 2 Hz, 1H) ppm; 13C NMR (CDCl3,
75 MHz) ı = 25.1 (2C), 29.1 (2C), 35.8, 40.4, 41.6, 111.98, 112.01
(2C), 120.0, 126.8, 127.1, 131.3, 133.0, 135.7, 140.1, 150.9 ppm; MS
(EI+) m/z = 277 (2, M+), 262 (10), 212 (58, M+−CH(CN)2), 197 (20,
M+−MeCH(CN)2), 182 (19), 170 (100, M+−CMe2CH(CN)2); HRMS
(EI+) calcd for C18H19N3 277.1579, found 277.1573; IR (NaCl) 766,
2969 cm−1
.
Ethyl 2-cyano-6-(4-cyanophenyl)-3,3,6-trimethylhept-4-en
oate (p-5d): pale yellow oil; 1H NMR (CDCl3, 300 MHz)
ı = 1.26–1.33 (m, 3H, –OCH2Me), 1.29 (s, 3H, –Me), 1.30 (s, 3H,
–Me), 1.41 (s, 6H, –Me), 3.39 (s, 1H, –CH(CN)CO2Et), 4.15–4.29 (m,
2H, –OCH2Me), 5.55 (d, J = 16.0 Hz, 1H, olefin), 5.69 (d, J = 16.0 Hz,
1H, olefin), 7.44 (AAꢀXXꢀ, J = 8.8 Hz, 2H, aromatic), 7.59 (AAꢀXXꢀ,
J = 8.8 Hz, 2H, aromatic) ppm; 13C NMR (CDCl3, 75 MHz) ı = 14.6
(–OCH2Me), 26.0 (–Me), 26.3 (–Me), 29.0 (2C, –Me), 39.8 (4◦), 41.3
(4◦), 49.7 (–CH(CN)CO2Et), 62.9 (–OCH2Me), 110.0 (4◦), 115.9 (4◦),
119.2 (4◦), 127.2 (2C), 131.9 (olefin), 132.2 (2C), 138.5 (olefin),
154.0 (ipso), 164.8 (C O) ppm; MS (EI+) m/z = 324 (7, M+), 212 (17,
M+−CH(CN)CO2Et), 196 (16), 170 (100, M+−CMe2CH(CN)CO2Et),
156 (20), 116 (16); HRMS (EI+) calcd for C20H24N2O2 324.1838,
found 324.1812; IR (NaCl) ꢀ = 1251, 1741 (C O), 2227 (C N),
1467, 2221 (C N), 2252 (w, C N), 2972 cm−1
.
Dimethyl 2-[trans-4-(4-cyanophenyl)-1,1,4-trimethylpent-
2-enyl]-malonate (p-5b): colourless oil; 1H NMR (300 MHz, CDCl3)
ı = 1.25 (s, 6H, –Me), 1.38 (s, 6H, –Me), 3.39 (s, 1H, –CH(CO2Me)2),
3.69 (s, 6H, –CO2Me), 5.57 (d, J = 15.9 Hz, 1H, olefin), 5.70 (d,
J = 15.9 Hz, 1H, olefin), 7.43 (AAꢀXXꢀ, J = 8.2 Hz, 2H, aromatic), 7.58
(AAꢀXXꢀ, J = 8.2 Hz, 2H, aromatic) ppm; 13C NMR (75 MHz, CDCl3)
ı = 26.3 (2C, –Me), 29.1 (2C, –Me), 38.6 (4◦), 41.2 (4◦), 52.4 (2C,
–CO2Me), 61.3 (–CH(CO2Me)2), 109.8 (4◦), 119.2 (–CN), 127.2
(2C), 132.0 (2C), 134.1 (olefin), 136.4 (olefin), 154.8 (ipso), 168.2
(2C, –CO2Me) ppm; MS (EI+) m/z = 343 (5, M+), 264 (24), 212
(40, M+−CH(CO2Me)2), 211 (34, M+−CH2(CO2Me)2), 196 (69), 173
(49), 170 (100, NC–C6H4–CMe2CH CH+); HRMS (EI+) calcd for
2972 cm−1
.
trans,trans-2,11-Dicyano-3,3,6,6,7,7,10,10-
octamethyldodeca-4,8-dienedinitrile (7a) [28,29]: colourless
blocks, mp 111–112 ◦C, 1H NMR (CDCl3, 300 MHz) ı = 1.00 (s,
12H), 1.36 (s, 12H), 3.61 (s, 2H), 5.36 (d, J = 15.8 Hz, 2H), 5.80 (d,
J = 15.8 Hz, 2H) ppm; 13C NMR (CDCl3, 75 MHz) ı = 23.4 (4C), 25.9
(4C), 35.9 (2C), 40.8 (2C), 41.5 (2C), 112.3 (4C), 129.8 (2C), 140.1
(2C) ppm; MS (EI+) m/z = 175 (39, M+/2), 110 (100, M+/2–CH(CN)2),
109 (35, M+/2–CH2(CN)2), 95 (30, M+/2–MeCH(CN)2); HRMS (CI+)
calcd for C22H31N4 ([M+H]+) 351.2549, found 351.2555; IR (NaCl)
C
20H25NO4 343.1784, found 343.1783; IR (NaCl) ꢀ = 1146, 1245,
1735 (C O), 1756 (C O), 2227 (C N), 2966 cm−1
.
Dimethyl 2-[trans-4-(2-cyanophenyl)-1,1,4-trimethylpent-
2-enyl]-malonate (o-5b): colourless oil; 1H NMR (300 MHz, CDCl3)
ı = 1.27 (s, 6H, –Me), 1.53 (s, 6H, –Me), 3.38 (s, 1H, –CH(CO2Me)2),
3.66 (s, 6H, –CO2Me), 5.58 (d, J = 16.1 Hz, 1H, olefin), 5.74 (d,
J = 16.1 Hz, 1H, olefin), 7.25–7.32 (m, 1H, aromatic), 7.45–7.55
(m, 2H, aromatic), 7.61–7.67 (m, 2H, aromatic) ppm; 13C NMR
(75 MHz, CDCl3) ı = 25.8 (2C, –Me), 29.2 (2C, –Me), 38.8 (4◦),
41.2 (4◦), 52.3 (2C, –CO2Me), 61.2 (–CH(CO2Me)2), 112.1 (4◦),
119.9 (4◦), 126.5, 127.0, 132.6, 135.5, 135.8 (olefin), 136.2 (olefin),
152.4 (ipso), 168.3 (2C, –CO2Me) ppm; MS (EI+) m/z = 343 (12, M+),
328 (60), 284 (44), 212 (100, M+−CH(CO2Me)2), 196 (80), 170
(63, NC–C6H4–CMe2CH CH+); HRMS (EI+) calcd for C20H25NO4
343.1784, found 343.1785; IR (NaCl) ꢀ = 1146, 1244, 1437, 1735
800, 1019, 1093, 1261, 2238 (w, C N), 2252 (w, C N), 2968 cm−1
;
Anal. calcd for C22H30N4: C, 75.39; H, 8.63; N, 15.98. Found: C,
75.15; H, 8.47; N, 15.86.
Dimethyl trans,trans-2,11-Bis(methoxycarbonyl)-3,3,6,6,7,
7,10,10-octamethyldodeca-4,8-dienedioate (7b): pale brown
oil; 1H NMR (300 MHz, CDCl3) ı = 0.89 (s, 12H), 1.23 (s, 12H), 3.36
(s, 2H, –CH(CO2Me)2), 3.68 (s, 12H, –CO2Me), 5.45 (d, J = 16.1 Hz,
2H, olefin), 5.49 (d, J = 16.1 Hz, 2H, olefin) ppm; 13C NMR (75 MHz,
CDCl3) ı = 23.5 (4C, 1◦), 26.3 (4C, 1◦), 38.9 (2C, 4◦), 40.9 (2C, 4◦), 52.4
(4C, –CO2Me), 61.4 (2C, –CH(CO2Me)2), 133.8 (2C, olefin), 135.8
(2C, olefin), 168.4 (4C, C O) ppm; MS (EI+) m/z = 241 (41, M+/2),
209 (10, M+/2−MeOH), 183 (17), 177 (26), 149 (13), 121 (28),
110 (19, M+/2−CH(CO2Me)2), 109 (100, M+/2−CH2(CO2Me)2),
101 (10), 95 (12, M+/2−MeCH(CO2Me)2); HRMS (EI+) calcd for
(C O), 1757 (C O), 2221 (C N), 2968 cm−1
.
Dimethyl 2-[trans-4-(3-cyanophenyl)-1,1,4-trimethylpent-
2-enyl]-malonate (m-5b): pale yellow oil; 1H NMR (300 MHz,

M. Ohashi et al. / Journal of Photochemistry and Photobiology A: Chemistry 214 (2010) 161–170
165
Scheme 6. Active methylene compounds (1a–1h).
C13H21O4 (M+/2) 241.1440, found 241.1435; IR (NaCl) ꢀ = 1142
(C–O), 1243, 1736 (C O), 1758 (C O), 2967 cm−1
.
Scheme 7. Alkenes (2a–2k and 4).
Diethyl trans,trans-2,11-diacetyl-3,3,6,6,7,7,10,10-octamet-
hyldodeca-4,8-dienedioate (7c): light yellow oil; 1H NMR (CDCl3,
300 MHz) ı = 0.91 (s, 12H), 1.19 (s, 6H), 1.20 (s, 6H), 1.26 (t,
J = 7.1 Hz, 6H, –CO2CH2Me), 2.19 (d, J = 0.3 Hz, 6H, –Ac), 3.41br (s,
2H, –CH(Ac)CO2Et), 4.15 (q, J = 7.1 Hz, 4H, –CO2CH2Me), 5.46 (d,
J = 17 Hz, olefin), 5.52 (d, J = 17 Hz, olefin) ppm; 13C NMR (CDCl3,
75 MHz) ı = 14.7 (2C, –CO2CH2Me), 23.4 (2C), 23.6 (2C), 26.5
(4C), 32.0 (2C), 39.3 (2C), 41.0 (2C), 61.3 (2C), 68.9 (2C), 133.9
(2C, olefin), 135.6 (2C, olefin), 168.8 (2C, –CO2Et), 202.9 (2C,
–C( O)Me) ppm; MS (EI+) m/z = 239 (42, M+/2), 121 (47), 110
(67, M+/2−CH(Ac)CO2Et), 109 (100, M+/2−CH2(Ac)CO2Et), 95 (77,
M+/2−MeCH(Ac)CO2Et), 67 (99); HRMS (EI+) calcd for C14H23O3
(M+/2) 239.1647, found 239.1649; IR (NaCl) ꢀ = 1142, 1366, 1718
(2C, –O–CMe2–O–), 132.6 (2C, olefin), 136.6 (2C, olefin), 164.6
(4C, C O) ppm; MS (EI+) m/z = 110 (100, (Me2C CH–)2•+), 109 (4),
95; HRMS (FAB+) neither M+ nor M+/2 was observed; IR (NaCl)
ꢀ = 1277, 1752, 2972 cm−1
.
2.7. Crystallographic data of photoproducts
CCDC-702041 and -702042 contains the supplementary crys-
tallographic data for 7a and 3aa, respectively. These data can be
obtained free of charge from The Cambridge Crystallographic Data
Centre via http://www.ccdc.cam.ac.uk/data request/cif.
(C O), 1734 (C O), 2973 cm−1
.
3. Results and discussion
Diethyl trans,trans-2,11-dicyano-3,3,6,6,7,7,10,10-octamet-
hyldodeca-4,8-dienedioate (7d): mixture (1:1) of dl- and meso-
isomers, brown oil; 1H NMR (CDCl3, 300 MHz) ı = 0.95 (s, 12H), 1.27
(s, 6H), 1.28 (s, 6H), 1.31 (dd, J = 7.1, 7.1 Hz, 6H, –OCH2Me), 3.367 (s,
2H, –CH(CN)CO2Et, one of the isomers), 3.373 (s, 2H, –CH(CN)CO2Et,
the other isomer), 4.20 (dq, J = 10.9, 7.1 Hz, 2H, –OCH2Me, one of
the isomers), 4.23 (dq, J = 10.9, 7.1 Hz, 2H, –OCH2Me, the other
isomer), 5.37 (d, J = 16.1 Hz, 2H, olefin), 5.64 (d, J = 16.1 Hz, 2H,
olefin) ppm; 13C NMR (CDCl3, 75 MHz) ı = 14.6 (2C, –OCH2Me),
23.41 (2C, 1◦, isomer A), 23.46 (2C, 1◦, isomers A and B), 23.50
(2C, 1◦, isomer B), 26.2 (2C, 1◦), 26.4 (2C, 1◦), 39.9 (2C, 4◦), 41.2
(2C, 4◦), 49.6 (2C, –CH(CN)CO2Et), 62.7 (2C, –OCH2Me), 116.1 (2C,
–CN), 131.7 (2C, olefin), 137.7 (2C, olefin), 165.0 (2C, C O) ppm;
MS (EI+) m/z = 222 (45, M+), 176 (12, M+−EtOH), 148 (11), 110
(29, M+−C•H(CN)CO2Et), 109 (100, M+−CH2(CN)CO2Et), 95 (13,
M+−MeCH(CN)CO2Et); HRMS (EI+) calcd for C13H20O2N (M+/2)
222.1494, found 222.1472; IR (NaCl) ꢀ = 1037, 1189 (C–O), 1250
3.1. Monoalkylation of active methylene compounds using
photochemical polar addition (PPA) and oxidative
photodimerization reactions
3.1.1. PPA reactions
In the earlier effort, we observed that photoirradiation of an
aqueous acetonitrile solution containing malononitrile (1a), 1,1-
diphenylethene (2a), lithium carbonate and a catalytic amount of
9-cyanophenanthrene (9-CP) leads to selective high yielding (91%)
formation of the anti-Markovnikov PPA product, ␣-monoalkylated
propanedinitrile 3aa (Schemes 3 and 6–8, and Table 1, entry 1) [28].
Importantly, an ␣,␣-dialkylated product is not generated in this
process. Most of 9-CP and excess 1a remain in the product mixture
and can be recovered. We believe that this reaction might serve
as a useful, safe, and environmentally friendly alkylation method-
ology that can be carried out under mild conditions (ambient
temperatures and weak bases) without the need to employ noble
(C–O), 1370, 1467, 1742 (C O), 2247 (w, C N), 2973 cm−1
.
trans,trans-3,12-Diacetyl-4,4,7,7,8,8,11,11-
octamethyltetradeca-5,9-diene-2,13-dione
(7e):
colourless
oil; 1H NMR (CDCl3, 300 MHz) ı = 0.92 (s, 12H), 1.16 (s, 12H), 2.18
(d, J = 0.4 Hz, 12H, –Ac), 3.72br (s, 2H, –CHAc2), 5.45 (d, J = 16.2 Hz,
2H, olefin), 5.52 (d, J = 16.2 Hz, 2H, olefin) ppm; 13C NMR (C6D6,
75 MHz) ı = 23.2 (4C), 26.2 (4C), 31.8 (4C, –C( O)Me), 39.4 (2C,
4◦), 40.7 (2C, 4◦), 75.9 (2C, –CHAc2), 134.0 (2C, olefin), 135.0 (2C,
olefin), 202.0 (4C, C O) ppm; MS (EI+) m/z = 209 (69, M+/2), 149 (46,
M+/2−AcOH), 110 (24, M+/2−Ac2CH), 109 (100, M+/2−Ac2CH2),
85 (27); HRMS (EI+) calcd for C13H21O2 (M+/2) 209.1541, found
209.1527; IR (NaCl) ꢀ = 665, 986, 1143, 1355, 1696 (C O), 1719,
2967 cm−1
.
2,9-Bis(4,4-dimethyl-3,5-dioxacyclohexa-2,6-dionyl)-
2,5,5,6,6,9-hexamethyldeca-3,7-diene (7f): white powder,
mp 133–135 ◦C; 1H NMR (CDCl3, 300 MHz) ı = 0.93 (s, 12H), 1.31 (s,
12H), 1.69 (s, 6H, –O–CMe2–O–), 1.72 (s, 6H, –O–CMe2–O–), 3.25
(s, 2H, 3◦), 5.41 (d, J = 16.1 Hz, 2H), 5.54 (d, J = 16.1 Hz, 2H) ppm; 13
C
NMR (CDCl3, 75 MHz) ı = 23.4 (4C), 27.3 (4C), 28.4 (2C, 4◦), 29.6
(2C, 4◦), 41.2 (2C, –O–CMe2–O–), 41.3 (2C, –O–CMe2–O–), 105.0
Scheme 8. Photosensitizers.

166
M. Ohashi et al. / Journal of Photochemistry and Photobiology A: Chemistry 214 (2010) 161–170
32 and 33) and the active “methyl” compound nitromethane (1g)
does not participate in this process (entry 34). While introduction
of the second alkyl group into the active “methine” compound,
2-methylpropanedinitrile (1h) is accomplished in 22% yield using
2a as the alkene, reaction of 1h with the more highly substituted
alkene 2b does not take place (entries 35 and 36).
Scheme 9. Enantiodifferentiating monoalkylation of 1a using PPA reaction.
3.1.2. Enantioselective carbon–carbon bond formation via PPA
The development of photosensitized (catalytic) stereoselec-
tive reactions that proceed via electron transfer pathways is a
challenging research topic [27,50–59]. A comprehensive study on
enantiodifferentiating PPA reactions of alcohols with 1,1-diphenyl-
1-alkenes has been carried out by Inoue and co-workers [53–55],
but knowledge is lacking on the use of carbon nucleophiles in these
processes.
Our current studies have uncovered the first enantiodifferen-
tiating PPA reaction of a carbon nucleophile. Specifically, a slight
enantiomeric excess (ee) of 0.7% was observed in the product 3ab of
the PPA reaction of 1a with 2b photosensitized by the bis-l-menthyl
ester of 1,4-naphthalenedicarboxylic acid 6 [53] (Scheme 9, and
Table 2, entry 2). A small increase of ee and a severe decrease of
yield take places when a solvent system with lower polarity is
employed (entry 3). This result suggests that lower solvent polarity
causes an enhancement in the face selective complexation between
the excited chiral photosensitizer 6 and the prochiral alkene
2b.
metals or alkyl halide required in conventional alkylation reactions
[8–21].
We have found that the efficiency of this reaction strongly
depends on the base used. Specifically, lower yields of 3aa are
observed when heavier alkali metal carbonates are used (entries
2–5). In addition, strong bases, such as sodium hydroxide and
potassium tert-butoxide, are not effective in promoting the reac-
tion (entries 6 and 7). In the absence of a base, the photoreaction
does not take place in aqueous acetonitrile (entry 8), but it does pro-
ceed in dry dimethyl sulfoxide (DMSO) in the presence of molecular
sieves (MS) 4A. We propose that DMSO acts as the “base” in this case
(entry 8) [44–46]. While the use of 9-CP results in the highest yield
of 3aa (entry 1), other photosensitizers, including phenanthrene
(Phen) which participates as a redox photosensitizer [47], can be
used for the reaction (entries 10 and 11).
The results of studies exploring the scope of alkenes that can
be employed in the reaction showed that alkyl substituents on the
vinylic positions of 1,1-diphenylethene lead to lower yields of the
products 3ab–3ad (entries 12–14). The dimethoxy derivative of
1,1-diphenylethene (2e), styrene (2f) and its alkylated derivatives
2g and 2h also participate in reactions that form the correspond-
ing photoproducts 3ae–3ah (entries 15–18). On the other hand,
reactions utilizing halogen-containing styrene derivatives (e.g., 2i
and 2j) afford polymeric mixtures and none of the desired adducts
(entries 19 and 20). Finally, alkyne 2k does not react under the
conditions employed (entry 21).
The photoinduced monoalkylation reaction takes place with a
variety of active methylene compounds, but in each case a dif-
ferent base-dependence is observed. In general, active methylene
compounds with weaker acidities require stronger bases. For exam-
ple, 2,2-diphenylethylation of dimethyl malonate (1b) proceeds
efficiently in the presence of stronger bases (entries 22–24), as
exemplified by the formation of 3ba in quantitative yield when
potassium tert-butoxide is used (entry 24). Other alkenes (2b,
2f–2h) also react with 1b (entries 25–28). Ethyl acetoacetate (1c)
and ethyl cyanoacetate (1d), which react in a manner similar to
1a and 1b (entries 29–31), can be applied in mild photochemical
␤-ketoester (e.g., acetoacetic [11–13] and malonic [14–17] ester)
synthetic procedures. However, adducts are not formed in reac-
tions of acetylacetone (1e) and Meldrum’s acid (1f) [48,49] (entries
3.1.3. Oxidative photodimerization reactions
Nucleophile-incorporated dimers are produced when 2,5-
dimethyl-2,4-hexadiene (4) is employed in the PPA reactions
[32,33]. For example, photoirradiation of an aqueous acetonitrile
solution, containing malononitrile (1a) and 4 along with lithium
carbonate and a catalytic amount of 9-CP, leads to formation of the
oxidative dimer 7a in a 52% yield (Scheme 4, and Table 3, entry 1)
[28]. The strength of the base used in this process affects the yield
of 7a. Accordingly, reactions with heavier alkali metal carbonates
result in slightly lower yields of 7a (entries 2–4). The reaction does
not proceed in the absence of base (entry 5) unless dry DMSO is
used as a solvent (entry 6) [44–46]. Lastly, photosensitizers other
than 9-CP can be used to promote the reaction albeit with lower
yields (entries 7–11).
Other active methylene compounds undergo monoalkylation
as well. Stronger bases, such as potassium tert-butoxide, promote
alkylation of 1b with diene 4 (entries 12–14) and similar reactions
take place with 1c–1f to form 7c–7f (entries 15–17, 19, and 20).
Instead of the acetylacetone (1e)–sodium hydroxide pair (entry 17),
magnesium acetylacetonate serves as a participant in this reaction
in the absence of base (entry 18).
Scheme 10. Plausible mechanism for the formation of 3 and 7.

M. Ohashi et al. / Journal of Photochemistry and Photobiology A: Chemistry 214 (2010) 161–170
167
Table 1
Photochemical polar addition of 1 into 2.a.
Entry
Active methylene compound
1a
Alkene
Sensitizer(s)
9-CP
Base
Product
Yieldb/%
1c
2c
2a
Li2CO3
Na2CO3
K2CO3
Rb2CO3
Cs2CO3
NaOH
3aa
91
66
68
23
15
13
Trace
0
31
27
44
52
19
0
3c
4c
5c
6
7d
KO-tBu
None
8
9e
10c
11c
12c
13
14
15c
16c
17c
18c
19
20
21
9,10-DCA
p-DCB, Phen
9-CP
Li2CO3
Li2CO3
2b
2c
2d
2e
2f
2g
2h
2i
3ab
3ac
3ad
3ae
3af
3ag
3ah
3ai
46
40
33
38
0
2j
2k
3aj
3ak
0
0
22
23
1b
2a
9-CP
Li2CO3
Cs2CO3
KO-tBu
KO-tBu
3ba
0
38
100
12
78
77
72
24d
25d
26d
27d
28d
2b
2f
2g
2h
3bb
3bf
3bg
3bh
29
1c
2a
9-CP
9-CP
NaOH
3ca
51
30
31
1d
2a
2b
Na2CO3
3da
3db
63
13
32d
33d
34d
1e
1f
2a
2a
2a
9-CP
9-CP
9-CP
9-CP
KO-tBu
KO-tBu
KO-tBu
Na2CO3
3ea
3fa
3ga
0
Complex
0
1g
1h
35
36
2a
2b
3ha
3hb
22
0
a
Conditions: 300-W high-pressure mercury lamp, Pyrex filter, active methylene compound (2.5 mmol), alkene (75 ␮mol), sensitizer(s) (25 ␮mol), base (1.25 mmol), in
MeCN (4 mL)–H2O (1 mL), under Ar, rt, 20 h.
b
Determined by 1H NMR based on the amount of 2 used.
Ref. [28].
In dry MeCN (5 mL).
In dry DMSO (5 mL) with MS4A (250 mg).
c
d
e
3.1.4. Plausible mechanisms
only a minor pathway since the concentration of the anion of 1a
is quite low (∼2 × 10−5 M) when a weak carbonate base is used,
which can be estimated from solubility of lithium carbonate and
pKa values of 1a and the carbonate [29].
When mono-olefins 2 are used as substrates, back electron
transfer (BET) from Sens•− to A• followed by protonation gives the
anti-Markovnikov adduct 3. On the other hand, allylic radical A•,
produced from the diene substrate, dimerizes to form 7.
In redox-photosensitized processes [47], Phen acts as an elec-
tron mediator between the alkene and the photosensitizer since
the Phen cation radical arising by SET to the excited state sen-
sitizer serves as the electron acceptor from the alkene and
diene.
The mechanism that we have proposed earlier (Scheme 10) [28]
appears to be applicable to PPA and oxidative photodimerization
reactions of the active methylene compounds. In this pathway,
photoinduced electron transfer (PET) from alkene 2 or diene 4 to
the singlet excited state of the electron-acceptor photosensitizer
(1Sens*) affords cation radicals 2•+ or 4•+, which react with the
anion of active methylene compound 1 to form benzylic or allylic
radical intermediates A•. Single electron transfer (SET) from the
anion of 1 to 1Sens* also occurs competitively, but it represents
Table 2
Enantiodifferentiating PPA of 1a into 2b.a.
Entry
Sensitizer
Solvents
Yieldb/%
eec/%
3.2. Tandem monoalkylation of active methylene compounds
using three-component coupling reactions
1d
2
3
9-CP
6
MeCN/H2O = 4/1
MeCN/H2O = 4/1
PhH/MeCN = 3/1
38
25
0.8
–
0.7
4.2
3.2.1. Three-component coupling reactions
a
Conditions: 300-W high-pressure mercury lamp, Pyrex filter, 1a (2.5 mmol), 2b
(75 ␮mol), sensitizer (25 ␮mol), Na2CO3 (1.25 mmol), solvents (5 mL in total), under
Ar, rt, 20 h.
Active methylene compounds also participate in photo-NOCAS
type, three-component coupling reactions [29]. For example, pho-
toirradiation of an aqueous acetonitrile solution containing 1a,
4, p-dicyanobenzene (p-DCB, terephthalonitrile), lithium carbon-
ate, and Phen, gives rise to generation of the ␣-monoalkylated
b
Determined by 1H NMR based on the amount of 2b used.
Determined by chiral GC.
Ref. [28].
c
d

168
M. Ohashi et al. / Journal of Photochemistry and Photobiology A: Chemistry 214 (2010) 161–170
Table 3
Oxidative photodimerization of 4 with 1.a.
Entry
Active methylene compound
1a
Sensitizer(s)
9-CP
Base
Product
Yieldb/%
1c
2
3
Li2CO3
Na2CO3
K2CO3
Cs2CO3
None
7a
52
50
46
46
0
31
43
47
37
25
22
4
5
6d
7
9,10-DCA
Na2CO3
8
9
10
11
m-DCB, Phen
o-DCB, Phen
p-DCB, Phen
TCNB, Phen
12
1b
9-CP
Na2CO3
NaOH
KO-tBu
7b
0
0
57
13
14e
15
1c
9-CP
9-CP
9-CP
NaOH
7c
41
41
16e
1d
KO-tBu
7d
17
18
1e
NaOH
None
7e
7e
45
11
Mg(acac)2
19e
1f
9-CP
9-CP
KO-tBu
KO-tBu
7f
(18)f
20e
1g
7g
Complex
a
Conditions: 300-W high-pressure mercury lamp, Pyrex filter, active methylene compound (2.5 mmol), 4 (75 ␮mol), sensitizer(s) (25 ␮mol), base (1.25 mmol), in MeCN
(4 mL)–H2O (1 mL), under Ar, rt, 20 h.
b
Determined by 1H NMR based on the amount of 4 used.
Ref. [28].
c
d
In dry DMSO (5 mL) with MS4A (250 mg).
e
In dry MeCN (5 mL).
f
Isolated yield (1H NMR spectrum of the crude mixture was too complex to determine the yield).
para-cyanophenyl product p-5a in high yield (84%) together with
the dimer 7a (23%) (Scheme 5, and Table 4, entry 1) [29]. Much
higher yields are obtained when heavier alkali metal carbonates
are used in this process (entries 2 and 3). A similar reaction with
o-dicyanobenzene (o-DCB, phthalonitrile) affords o-5a in modest
yield (entry 5), but the meta analogue m-DCB (isophthalonitrile)
does not undergo this NOCAS type reaction to produce m-5a (entry
7). It should be noted that these reactions occur in the absence of
the mediator Phen, but the yield of o-5a is lower in this case (entries
4, 6, and 8).
m-5a when potassium tert-butoxide is used as the base (entries
9–11). The use of strong bases also enhances the yields of tandem
alkylation reactions of 1c–1e (entries 12–14).
Overall, this noble metal-free photoreaction serves as
a
novel methodology for substitution reactions at aryl–cyano cen-
ters, which have precedence but are still challenging tasks
[34–38,60–63].
3.2.2. Plausible mechanism
The mechanistic route followed in the three-component cou-
pling reaction begins with photoinduced SET to afford 4•+ and
DCB•− (Scheme 11) [29,47]. The radical cation 4•+ is trapped by
the anion of 1 to form an allylic radical intermediate A•, which
When the active methylene compound 1b is employed as the
substrate not only are adducts o- and p-5a formed from reactions of
the corresponding dicyanobenzenes, but m-DCB also reacts to form
Table 4
Three-component photoreaction of 1, 4, and dicyanobenzenes (DCBs).a.
Entry
Active methylene compound
Dicyanobenzene
Sensitizer
Phen
Base
Products (yieldsb/%)
1c
2c
3c
4
1a
p-DCB
Li2CO3
Na2CO3
K2CO3
p-5a (84)
(87)
(96)
(87)
o-5a (52)
(38)
7a (23)
(25)
(25)
(26)
(37)
(45)
(47)
(46)
None
Phen
None
Phen
None
Na2CO3
5c
6
o-DCB
7c
8
m-DCB
m-5a (0)
(0)
9d
10d
11d
1b
p-DCB
o-DCB
m-DCB
Phen
KO-tBu
p-5b (76)
o-5b (47)
m-5b (13)
7b (35)
(38)
(30)
12
1c
1d
1e
p-DCB
p-DCB
p-DCB
Phen
Phen
Phen
NaOH
KO-tBu
NaOH
p-5c (97)
p-5d (73)
p-5e (76)
7c (32)
7d (31)
7e (22)
13d
14
a
Conditions: 300-W high-pressure mercury lamp, Pyrex filter, active methylene compound (2.5 mmol), 4 (75 ␮mol), dicyanobenzene (25 ␮mol), sensitizer (25 ␮mol), base
(1.25 mmol), in MeCN (4 mL)–H2O (1 mL), under Ar, rt, 20 h.
b
Determined by 1H NMR based on the amount of dicyanobenzene (for 5) and 4 (for 7) used.
Ref. [29].
In dry MeCN (5 mL).
c
d

M. Ohashi et al. / Journal of Photochemistry and Photobiology A: Chemistry 214 (2010) 161–170
169
Scheme 11. Plausible mechanism for the formation of 5 and 7.
couples with DCB•− within a solvent cage to give B−. Stabilization
[13] A.P. Krapcho, Synthesis (1982) 893–914.
of the negative charge in B− by an ortho- or para-disposed cyano
group is crucial in order for the radical coupling process to pro-
ceed smoothly. Elimination of cyanide ion from the ipso-position
of B− then regenerates the aromatic ring and affords the three-
component coupling product 5. When A• diffuses out of the solvent
cage, it undergoes dimerization to produce 7.
[14] A.C. Cope, H.L. Holmes, H.O. House, Org. React. 9 (1957) 107–331.
[15] J.E. McMurry, J.H. Musser, J. Org. Chem. 40 (1975) 2556–2557.
[16] L.-F. Tiete, G.V. Kiedrowski, Tetrahedron Lett. 22 (1981) 219–222.
[17] B.M. Trost, W.P. Conway, P.F. Strege, T.J. Dietsche, J. Am. Chem. Soc. 96 (1974)
7165–7167.
[18] E. Díez-Barra, A. de la Hoz, A. Moreno, P. Sánchez-Verdú, Synthesis (1989)
391–393 (cited therein).
[19] W.R.H. Hurtley, J. Chem. Soc. (1929) 1870–1873.
[20] R.O. Hutchins, B.E. Maryanoff, Org. Synth. 53 (1973) 21–25.
[21] H. Mukae, H. Maeda, K. Mizuno, Angew. Chem. Int. Ed. 45 (2006) 6558–6560;
H. Mukae, H. Maeda, K. Mizuno, Angew. Chem. 118 (2006) 6708–6710.
[22] L.Y. Cho, J.R. Romero, Tetrahedron Lett. 36 (1995) 8757–8760.
[23] A.V. Bogatskii, D.B. Furman, L.N. Colonditskaya, Zh. Org. Khim. 2 (1966) 59–62;
A.V. Bogatskii, D.B. Furman, L.N. Colonditskaya, Chem. Abstr. 64 (1966) 14125.
[24] A.M. Cardarelli, M. Fagnoni, M. Mella, A. Albini, J. Org. Chem. 66 (2001)
7320–7327.
[25] K. Mizuno, M. Ikeda, Y. Otsuji, Chem. Lett. (1988) 1507–1510.
[26] T. Hayamizu, M. Ikeda, H. Maeda, K. Mizuno, Org. Lett. 3 (2001) 1277–1280.
[27] T. Hayamizu, H. Maeda, K. Mizuno, J Org. Chem. 69 (2004) 4997–5004.
[28] M. Ohashi, K. Nakatani, H. Maeda, K. Mizuno, Org. Lett. 10 (2008) 2741–2743.
[29] M. Ohashi, K. Nakatani, H. Maeda, K. Mizuno, J. Org. Chem. 73 (2008) 8348–8351.
[30] R.A. Neunteufel, D.R. Arnold, J. Am. Chem. Soc. 95 (1973) 4080–4081.
[31] M. Yasuda, K. Mizuno, Photochemical polar addition, in: H.S. Nalwa (Ed.),
Handbook of Photochemistry and Photobiology, vol. 2, American Scientific
Publishers, 2003 (Chapter 8).
4. Conclusion
This study has led to the development of two novel photochemi-
cal reactions, which result in ␣-monoalkylation of active methylene
compounds. The first involves the introduction of electron-rich
alkenes via a photochemical polar addition (PPA) pathway and
the second corresponds to tandem introduction of a diene and
cyanoarene groups via a photo-NOCAS mechanism. We believe
that these reactions will find utility as safe and environmentally
friendly synthetic methods, since they proceed under mild con-
ditions (ambient temperature, without noble metals and alkyl
halides, and in the presence of weak bases such as alkali metal
carbonate). Of particular interest are photoinduced reactions of
␤-ketoesters, which can serve as replacements of conventional.
acetoacetic and malonic ester synthetic protocols.
[32] K. Mizuno, C. Pac, H. Sakurai, J. Am. Chem. Soc. 96 (1974) 2993–2994.
[33] M. Ohashi, H. Maeda, K. Mizuno, Chem. Lett. 35 (2006) 482–483.
[34] D. Mangion, D.R. Arnold, Acc. Chem. Res. 35 (2002) 297–304.
[35] D. Mangion, D.R. Arnold, in: W.M. Horspool, F. Lenci (Eds.), CRC Handbook of
Organic Photochemistry and Photobiology, 2nd ed., CRC Press, 2004 (Chapter
40).
[36] K. Mizuno, Y. Otsuji, Top. Curr. Chem. 169 (1994) 301–346.
[37] A.N. Frolov, Russ. J. Org. Chem. 34 (1998) 139–161;
A.N. Frolov, Zh. Org. Khim. 34 (1998) 167–189.
[38] Z.-F. Lu, Y.-M. Shen, J.-J. Yue, H.-W. Hu, J.-H. Xu, J. Org. Chem. 73 (2008)
8010–8015.
Acknowledgements
We thank Dr. Akihiro Nomoto at Osaka Prefecture University for
X-ray crystallographic analysis.
[39] H. Tomioka, M. Kanda, Chem. Lett. (1990) 2223–2226.
[40] J.K. Williams, E.L. Martin, W.A. Sheppard, J. Org. Chem. 31 (1966) 919–922.
[41] Z.-L. Wu, Z.-Y. Li, Tetrahedron: Asymm. 14 (2003) 2133–2142.
[42] D.P. Curran, M.H. Chen, E. Spletzer, C.M. Seong, C.T. Chang, J. Am. Chem. Soc.
111 (1989) 8871–8878.
This work was partially supported by Grant-in-Aids for Scientific
Research on Priority Areas (429) (16033252), Scientific Research (B)
(Nos. 15350026 and 20044027), JSPS Fellows (No. 20-4975), and the
Cooperation for Innovative Technology and Advanced Research in
Evolutional Area (CITY AREA) program from the Ministry of Educa-
tion, Culture, Sports, Science and Technology (MEXT) of Japan.
[43] G. Swoboda, A. Eitel, J. Swoboda, F. Wessely, Monatsh. Chem. 95 (1964)
1355–1375.
[44] T. Watahiki, S. Ohba, T. Oriyama, Org. Lett. 5 (2003) 2679–2681.
[45] T. Kakinuma, R. Chiba, T. Oriyama, Chem. Lett. 37 (2008) 1204–1205.
[46] R. Chiba, T. Oriyama, Chem. Lett. 37 (2008) 1218–1219.
[47] T. Majima, C. Pac, A. Nakasone, H. Sakurai, J. Am. Chem. Soc. 103 (1981)
4499–4508.
References
[48] A.N. Meldrum, J. Chem. Soc. 93 (1908) 598–601 (with misidentified structure).
[49] D. Davidon, S.A. Bernhard, J. Am. Chem. Soc. 70 (1948) 3426–3428 (with cor-
rected structure).
[50] V. Ramamurthy, K. Schanze (Eds.), Molecular and Supramolecular Photochem-
istry, Marcel Dekker, New York, 1999.
[1] C.-J. Li, Acc. Chem. Res. 42 (2009) 335–344.
[2] V. Ritleng, C. Sirlin, M. Pfeffer, Chem. Rev. 102 (2002) 1731–1770.
[3] G. Dyker, Angew. Chem. Int. Ed. 38 (1999) 1698–1712;
G. Dyker, Angew. Chem. 111 (1999) 1808–1822.
[4] B.A. Arndtsen, R.G. Bergman, T.A. Mobley, T.H. Peterson, Acc. Chem. Res. 28
(1995) 154–162.
[51] Y. Inoue, Chem. Rev. 92 (1992) 741–770.
[52] Y. Inoue, Nature 436 (2005) 1099–1100.
[53] S. Asaoka, T. Kitazawa, T. Wada, Y. Inoue, J. Am. Chem. Soc. 121 (1999)
8486–8498.
[5] T. Naota, H. Takaya, S.-I. Murahashi, Chem. Rev. 98 (1998) 2599–2660.
[6] P.T. Anastas, J.C. Warner, Green Chemistry: Theory and Practice, Oxford Uni-
versity Press, New York, 1998.
[54] Y. Nishiyama, M. Kaneda, S. Asaoka, R. Saito, T. Mori, T. Wada, Y. Inoue, J. Phys.
Chem. A 111 (2007) 13432–13440.
[7] R. Noyori, Chem. Commun. (2005) 1807–1811.
[8] F. Freeman, Chem. Rev. 69 (1969) 591–624.
[55] G. Fukuhara, T. Mori, Y. Inoue, J. Org. Chem. 74 (2009) 6714–6727.
[56] A. Bauer, F. Westkämper, S. Grimme, T. Bach, Nature 436 (2005) 1139–1140.
[57] T. Hayamizu, H. Maeda, M. Ikeda, K. Mizuno, Tetrahedron Lett. 42 (2001)
2361–2364.
[9] A.J. Fatiadi, Synthesis (1978) 165–204.
[10] A.J. Fatiadi, Synthesis (1978) 241–282.
[11] R. Adams, R.M. Kamm, Org. Synth. 4 (1925) 11–12.
[12] A.P. Krapcho, Synthesis (1982) 805–822.

170
M. Ohashi et al. / Journal of Photochemistry and Photobiology A: Chemistry 214 (2010) 161–170
[58] K. Mizuno, T. Hayamizu, H. Maeda, Pure Appl. Chem. 75 (2003) 1049–
1054.
[59] T. Hayamizu, H. Maeda, K. Mizuno, J. Org. Chem. 69 (2004) 4997–5004.
[60] M. Tobisu, N. Chatani, Chem. Soc. Rev. 37 (2008) 300–307.
[61] M. Tobisu, Y. Kita, N. Chatani, J. Am. Chem. Soc. 128 (2006) 8152–8153.
[62] Y. Nakao, S. Oda, T. Hiyama, J. Am. Chem. Soc. 126 (2004) 13904–13905.
[63] M. Zhang, Z.-F. Lu, Y. Liu, G. Grampp, H.-W. Hu, J.-H. Xu, Tetrahedron 62 (2006)
5663–5674.