Decarboxylative radical addition of N-Boc-amino acids to acrylonitrile via photoinduced electron transfer using 1,4-dicyanonaphthalene

Article abstract of DOI:10.1007/s11164-012-0657-z

Decarboxylative radical addition of N-(t-butoxycarbonyl)amino acids to acrylonitrile was achieved by excitation of 1,4-dicyanonaphthalene. The photochemical decarboxylation was highly dependent on the dicyanoarenes used as electron acceptors and on addition of a base. The photoreaction proceeded smoothly to yield the decarboxylative adduct even in the presence of only a catalytic amount of 1,4-dicyanonaphthalene.

Full text of DOI:10.1007/s11164-012-0657-z

Res Chem Intermed (2013) 39:397–402
DOI 10.1007/s11164-012-0657-z
Decarboxylative radical addition of N-Boc-amino acids
to acrylonitrile via photoinduced electron transfer using
1,4-dicyanonaphthalene
•
Yasuharu Yoshimi Shota Hayashi
•
Keisuke Nishikawa Yoshiki Okita
•
•
•
Kousuke Maeda Toshio Morita Tatsuya Itou
•
Received: 2 November 2011 / Accepted: 2 December 2011 / Published online: 3 July 2012
Ó Springer Science+Business Media B.V. 2012
Abstract Decarboxylative radical addition of N-(t-butoxycarbonyl)amino acids to
acrylonitrile was achieved by excitation of 1,4-dicyanonaphthalene. The photo-
chemical decarboxylation was highly dependent on the dicyanoarenes used as
electron acceptors and on addition of a base. The photoreaction proceeded smoothly
to yield the decarboxylative adduct even in the presence of only a catalytic amount
of 1,4-dicyanonaphthalene.
Keywords Decarboxylative radical addition Á N-Boc-amino acids Á Acrylonitrile Á
1,4-Dicyanonaphthalene Á Photoinduced electron transfer
Introduction
Decarboxylative radical addition of carboxylic acids to alkenes is one of the most
important types of C–C bond formation in organic synthesis, because carboxylic acids
occur widely in nature and are readily available commercially. This transformation is
usually performed via Barton decarboxylation; however, this requires esterification
of carboxylic acids to thiohydroxamic esters as precursors, and use of excess alkene
[1–4]. A photochemical method involving intramolecular photoinduced electron
This paper is dedicated to Professor Kazuhiko Mizuno of Osaka Prefecture University on the occasion of
his retirement.
Y. Yoshimi (&) Á S. Hayashi Á K. Nishikawa Á Y. Okita Á K. Maeda Á T. Morita
Department of Applied Chemistry and Biotechnology, Graduate School of Engineering,
University of Fukui, 3-9-1 Bunkyo, Fukui 910-8507, Japan
e-mail: yyasuharu@chem.wisc.edu; yyoshimi@u-fukui.ac.jp
T. Itou
Department of Applied Chemistry, College of Life Sciences, Ritsumeikan University,
1-1-1 Noji-Higashi, Kusatsu 525-8577, Japan
123

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Y. Yoshimi et al.
Phen *
1,4-DCB
ν
h
Phen; phenanthrene
1,4-DCB; 1,4-dicyanobenzene
Phen
1,4-DCB
Phen
O
O
O
H+
X
X
H+
CO2
X
X
R
R
O
R
O
R
OH
R
R
R
Scheme 1 Decarboxylative radical addition of carboxylic acids to alkenes via PET
transfer (PET) of 3-(N-phthalimido)adamantane-1-carboxylic acids, which yields
decarboxylative radical adducts with alkenes, can also be used [5].
We recently reported the decarboxylative radical addition of a variety of N-(t-
butoxycarbonyl)amino acids (N-Boc-amino acids) to electron-deficient alkenes, for
example acrylonitrile, ethyl acrylate, acrylic acid, and phenyl vinyl sulfone, in a
redox-photosensitized reaction [6–8] (Scheme 1). Single-electron transfer (SET)
from the carboxylate ion to the photogenerated radical cation of phenanthrene
(Phen) proceeds to form an alkyl radical via decarboxylation of a carboxyl radical
[9–14]. The alkyl radicals generated react with alkenes to produce adduct radicals.
SET from the radical anion of 1,4-dicyanobenzene (1,4-DCB) and protonation lead
to formation of the adduct in high yield, even in the presence of only one equivalent
of alkene. Furthermore, this photodecarboxylation is applicable to intramolecular
radical addition to alkenes, inducing cyclizations to macrocyclic lactones [9]. This
discovery led us to investigate a more simple photochemical method that involves
use of dicyanoarenes. Although the excited states of dicyanoarenes have been
shown to decarboxylate carboxylate ions with generation of alkyl radicals [11, 15],
decarboxylative radical addition to alkenes has not yet been investigated. In this
study, we investigated decarboxylative radical addition of carboxylic acids, for
example N-Boc-amino acids, to acrylonitrile 2 by use of dicyanoarenes.
Results and discussion
Initially, photodecarboxylative addition of N-Boc-valine 1a to 2 in a variety of
dicyanoarenes was examined, as shown in Table 1. Excitation of an aqueous
acetonitrile solution (CH3CN–H2O 9:1) containing 1,4-dicyanonaphthalene (DCN,
20 mM), 1a (20 mM), and 2 (20 mM) with a 400-W high-pressure mercury lamp
through a Pyrex filter (k [ 300 nm) under an argon atmosphere for 6 h at room
temperature afforded the adduct 3a in 80 % yield (entry 1 in Table 1). By
comparison, using only DCN produced 3a via decarboxylation in a yield similar to
that obtained from our photoreaction using Phen and 1,4-DCB [9]; however,
prolonged irradiation or a more powerful light source was required. It is noteworthy
that a catalytic amount of DCN (10, 5 mM) resulted in a similar product yield of 3a
by prolonged irradiation (entries 2 and 3). Use of 1,4-DCB, 1,3-DCB, and 1,2-DCB
instead of DCN did not afford 3a (entries 4–6). With 1,4-DCB, the substituted
123

Decarboxylative radical addition
399
Table 1 Decarboxylative radical addition of 1 to 2 using dicyanoarene
R
ν
R
h
R
dicyanoarene
OH
+
CN
BocHN
BocHN
BocHN
CN
+
CH
3CN/H2O=9:1
O
CN
1a;R= CH(CH3)2 (20mM)
N-Boc-valine
4a
2 (20mM)
3a-b
Ph(20mM)
1b;R = CH2
N-Boc-phenylalanine
Entry
1
Dicyanoarene
Irradiation time (h)
Yield of 3 (%)a
1
2
3
4
5
6
7c
8c
9c
a
1a
1a
1a
1a
1a
1a
1a
1a
1b
DCN (20 mM)
DCN (10 mM)
DCN (5 mM)
6
18
36
18
18
18
3
80
72
75
0 (8)b
1,4-DCB (20 mM)
1,3-DCB (20 mM)
1,2-DCB (20 mM)
DCN (20 mM)
DCN (5 mM)
0
0
92
12
3
91
DCN (20 mM)
61
Isolated yield
b
The value in parentheses is the yield of 4a
c
Addition of 1 equiv NaOH
cyanobenzene 4a was obtained in a low yield (8 %, entry 4). As previously reported
by us [11], these results could be attributed to the lower absorption of these
dicyanobenzenes at 313 nm than that of DCN, and to reaction of the generated alkyl
radical with the radical anion of 1,4-DCB to produce 4a. Addition of one equivalent
of NaOH to this solution accelerated the photoreaction, and an improved yield of 3a
was obtained, even for a shorter irradiation time (entry 7), because decarboxylation
of a carboxylate ion is more efficient than that of the corresponding carboxylic acid
[9–11, 13, 14]. The photoreaction using a catalytic amount of DCN in the presence
of one equivalent of NaOH also led to a high yield of 3a (entry 8). Thus, DCN was
proved to serve as a photocatalyst in the decarboxylative radical addition of
carboxylic acids to alkenes. The decarboxylative adduct 3b in the photoreaction of
N-Boc-phenylalanine 1b to 2 was obtained under the same conditions (entry 9);
however, this resulted in a lower yield of 3b and the formation of by-products.
Further study of this photoreaction is now in progress and will be reported
elsewhere.
The fluorescence of DCN in the aqueous acetonitrile solution was efficiently
quenched by the sodium salt of 1a, as shown in Fig. 1, and the rate constant for
fluorescence quenching (kq) was calculated as 3.95 9 109 M-1 -1
from the Stern–
s
Volmer plot I0/I = 1 ? kqs[Q], where I0 is the fluorescence intensity of DCN at
385 nm without the sodium salt of 1a, I is the observed fluorescence intensity of
DCN at 385 nm with the sodium salt of 1a, s, = 10.1 ns [16], is the fluorescence
lifetime of DCN, and [Q] is the concentration of the sodium salt of 1a. This
indicates that PET from the carboxylate ion of 1a to the excited state of DCN
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Y. Yoshimi et al.
500
400
300
200
100
0
sodium salt of 1a = 0 M
0.83 x 10-3
M
1.67 x 10-3 M
2.50 x 10-3 M
3.33 x 10-3 M
4.17 x 10-3 M
5.00 x 10-3 M
350
400
450
500
Wavelength [nm]
Fig. 1 Fluorescence quenching of DCN by the sodium salt of 1a in aqueous acetonitrile (CH3CN–H2O
9:1, kEX = 280 nm)
occurred smoothly. The Rehm–Weller equation [17] confirms that the PET is an
exothermic process, as indicated by the negative DG value (-97.4 kJ mol-1
;
DG = 96.49 [E(DÁ?/D) - E(A/AÁ-)] - Es) which was calculated using the reduc-
tion potential (E(A/AÁ-); -1.28 V vs. SCE in acetonitrile) [15], the excited singlet
energy (Es; 333 kJ mol-1) [15] of DCN, and the oxidation potential of the aliphatic
carboxylate ion (E(DÁ?/D); ?1.16 V vs. SCE in acetonitrile) [18].
On the basis of these results, we propose a mechanism for this photoreaction
(Scheme 2). PET from the carboxylate ion to the excited state of DCN leads to the
formation of the radical anion of DCN and the carboxyl radical 5. The alkyl radical
6 formed by decarboxylation of 5 reacts with 2 to produce the adduct radical 7. SET
from the radical anion of DCN, and protonation, yields the adduct 3. The fact that a
high yield of 3 was obtained, even in the presence of only one equivalent of 2, can
be explained as follows. The large rate constants for decarboxylation of the aliphatic
ν
h
*
DCN
DCN
DCN; 1,4-dicyanonaphthalene
DCN
O
O
O
H+
2
CN
H+
CO
2
CN
CN
R
R
O
R
R
O
R
R
R
OH
5
3
6
7
1
Scheme 2 Plausible mechanism for photochemical decarboxylation using DCN
123

Decarboxylative radical addition
401
carboxyl radical 5 [19] and for addition of the electron-rich alkyl radical 6 to the
electron-deficient alkene 2 [4, 20] lead to the selective formation of 7. SET from the
radical anion of DCN to 7 occurs smoothly because 7 is highly electron-deficient
and because of the relatively long lifetime of the radical anion of DCN [21–23].
Conclusion
In conclusion, we found that DCN can work as a photochemical catalyst in
decarboxylative radical addition of N-Boc-amino acids to acrylonitrile. The highest
yield of 3 was achieved by addition of one equivalent of NaOH. This is a simple
method, because DCN is the only photosensitizer used in the photoreaction. Further
investigation of the applications of this photoreaction is currently in progress.
Experimental
General
An IR spectrum was recorded on a Jasco FT/IR-620 spectrometer. 1H and 13C NMR
spectra were recorded on a Jeol JNM-AL500 (500 and 125 MHz) spectrometer
using solutions in CDCl3 containing tetramethylsilane as internal standard.
Chemical shifts (d) are expressed in ppm. A high-resolution mass spectrum
(HRMS) was obtained by use of a Jeol JMS-700T spectrometer. A Riko UV-400HA
400-W high-pressure mercury arc lamp was used as the light source. Dicyanoarenes
were recrystallized from hexane and EtOAc. Column chromatography was
conducted on a silica gel column (Wakogel C-200).
General procedure for photoreaction of N-Boc-valine 1a to acrylonitrile 2
An aqueous CH3CN solution (CH3CN 54 ml, H2O 6 ml) of 1a (1.2 mmol, 20 mM)
and DCN (1.2 mmol, 20 mM) in four Pyrex vessels (18 9 180 mm) was purged
with argon for 10 min, and to this was added 2 (1.2 mmol, 20 mM) under an argon
atmosphere. The mixture was irradiated with the 400-W high-pressure mercury
lamp for 6 h. The solvent was subsequently evaporated to yield the crude product.
The adduct 3 was isolated by column chromatography on silica gel using hexane
and EtOAc as eluents. A similar photoreaction of 1b with 2 was performed under
the same conditions.
3a: white solid; m.p. 76 °C; IR (KBr, cm-1) m 3383, 2964, 2249, 1680, 1512; 1H
NMR (500 MHz, CDCl3) d 4.34 (brd, 0.75H, NH), 4.03 (brs, 0.10H, NH), 3.48–3.43
(m, 1H), 2.46–2.34 (m, 2H), 1.91 (m, 1H), 1.71 (m, 1H), 1.62 (m, 1H), 1.44 (s, 9H),
0.94–0.90 (m, 6H); 13C NMR (125 MHz, CDCl3) d 155.9, 119.8, 79.6, 55.2, 32.3,
29.2, 28.3, 19.1, 17.8, 14.6; HRMS (FAB) calcd for C12H23N2O2: 227.1761, found:
227.1738 [M ? H]?.
3b: white solid; m.p. 100 °C; IR (KBr, cm-1) m 3373, 2977, 2242, 1687, 1504; 1H
NMR (500 MHz, CDCl3) d 7.39–7.15 (m, 5H), 4.44 (brs, 1H, NH), 3.88–3.82
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Y. Yoshimi et al.
(m, 1H), 2.84–2.70 (m, 2H), 2.44–2.31 (m, 2H), 1.91 (m, 1H), 1.69 (m, 1H), 1.40
(s, 9H); 13C NMR (125 MHz, CDCl3) d 155.4, 137.0, 129.2, 128.6, 126.8, 119.5,
79.7, 51.1, 41.3, 30.5, 28.9, 14.1; HRMS (FAB) calcd for C16H23N2O2: 275.1760,
found: 275.1712 [M ? H]?.
Acknowledgments This work was supported by a Sasakawa Scientific Research Grant, Japan.
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