N-Acryloyl amino acid esters and peptides as radical acceptors in photoinduced decarboxylative radical reaction

Article abstract of DOI:10.1016/j.jphotochem.2015.11.001

The photoinduced electron transfer (PET) promoted decarboxylative radical additions of carboxylic acids using N-acryloyl amino acid esters and peptides as radical acceptors smoothly afforded the corresponding modified amino acids and peptides under mild reaction conditions. The radical additions of α-amino acids led to the formation of γ- and α-dipeptide, and peptides underwent peptide coupling via decarboxylation.

Full text of DOI:10.1016/j.jphotochem.2015.11.001

Journal of Photochemistry and Photobiology A: Chemistry 317 (2016) 50–55
Contents lists available at ScienceDirect
Journal of Photochemistry and Photobiology A:
Chemistry
journal homepage: www.elsevier.com/locate/jphotochem
N-Acryloyl amino acid esters and peptides as radical acceptors in
photoinduced decarboxylative radical reaction
*
Kazuyuki Osaka, Mai Sugie, Mugen Yamawaki, Toshio Morita, Yasuharu Yoshimi
Department of Applied Chemistry and Biotechnology, Graduate School of Engineering, University of Fukui, 3-9-1 Bunkyo, Fukui 910-8507, Japan
A R T I C L E I N F O
A B S T R A C T
Article history:
The photoinduced electron transfer (PET) promoted decarboxylative radical additions of carboxylic acids
using N-acryloyl amino acid esters and peptides as radical acceptors smoothly afforded the
corresponding modified amino acids and peptides under mild reaction conditions. The radical additions
Received 8 September 2015
Accepted 2 November 2015
Available online 14 November 2015
of
a
-amino acids led to the formation of
g- and
a
-dipeptide, and peptides underwent peptide coupling
via decarboxylation.
This paper is dedicated to Prof. Yoshihisa
Inoue of Osaka University on his retire-
ment.
ã 2015 Elsevier B.V. All rights reserved.
Keywords:
Photoinduced decarboxylative radical
reaction
N-Acryloyl peptides
1. Introduction
of this early effort demonstrated that this photochemical process is
an efficient method for forming new CÀÀC bonds from aliphatic
carboxylic acids under mild reaction conditions.
The modifications of amino acids and peptides are one of the
current attractive challenges in organic synthesis [1,2], because
they play an important role not only in biochemistry [3–5], but also
in nanomaterials such as nanotubes [6,7]. Although diverse
methods have been used for the modification of amino acids
This finding encouraged us to investigate the intermolecular
radical addition of carboxylic acids to N-acryloyl amino acid esters
and peptides as radical acceptors in PET promoted decarboxylative
radical reactions, because the N-alkylcarbonyl amino acids and
peptides obtained by the photoreaction are potential pharmaceu-
tical agonists and inhibitors [18,19]. The results of this effort that
led to the development of a new method for the modification of
amino acids and peptides using N-acryloyl amino acid esters and
peptides are described below.
and peptides,
a radical method is interesting for directly
introducing functional group into amino acids and peptides [8],
because it is often difficult to use ionic reactions to form new CÀÀC
bonds in amino acids and peptides.
Recently, we reported a decarboxylative radical reaction of
aliphatic carboxylic acids that is promoted by the radical cation of
phenanthrene (Phen) via photoinduced electron transfer (PET)
between Phen and 1,4-dicyanobenzene (1,4-DCB) (Scheme 1) [9–
17]. The alkyl radicals, produced by a single electron transfer from
carboxylates to the Phen radical cation followed by the decarbox-
ylation of the intermediate carboxy radicals, reacted with a variety
of reagents such as electron-deficient alkenes, oxime ethers, and
thiols, to produce addition [11,13–17], reduction [9,12], and
substitution [10] products in high yields. Particularly, an efficient
intermolecular radical addition was achieved by this methodology,
even with only 1 equiv of electron-deficient alkenes in the
presence of catalytic amounts of Phen and 1,4-DCB [16]. The results
2. Experimental
2.1. General
All the reagents and solvents were used as received without
further purification. The 1H NMR spectra were recorded in CDCl3
containing tetramethylsilane as the internal standard using either
a 300 or 500 MHz spectrometer. The 13C NMR spectra were
recorded using either a 75 or 125 MHz spectrometer. The high
resolution mass spectra were obtained using a time-to-flight mass
spectrometer with a Fourier transform ion cyclotron resonance
mass spectrometer with ESI positive mode. The light source was
high-pressure mercury arc lamp. The spectra data of compounds
2 a,b [20,21] and 4 [22] have been reported previously.
* Corresponding author. Fax: +81 776 27 8747.
E-mail address: yyoshimi@u-fukui.ac.jp (Y. Yoshimi).
http://dx.doi.org/10.1016/j.jphotochem.2015.11.001
1010-6030/ã 2015 Elsevier B.V. All rights reserved.

K. Osaka et al. / Journal of Photochemistry and Photobiology A: Chemistry 317 (2016) 50–55
51
*
Phen
h
1,4-DCB
Phen =
Phen
NC
1,4-DCB =
CN
X
Phen
1,4-DCB
R
O
C
O
C
O
C
X
X
+ H
X
R
R
R
O
R
OH
R
O
X = CN, CO2CH3, CO2H, SO2Ph
-CO2
R
Scheme 1. PET promoted decarboxylative radical addition of carboxylic acids to electron-deficient alkenes.
2.2. Synthesis of N-acryloyl amino acid esters 2
2.5. Characterization data
Acryloyl chloride (1.5 equiv) was added to a solution of amino
acid methyl ester hydrochloride (1.0 equiv) and i-Pr2NEt (2.0 equiv)
in CHCl3 at 0 ꢀC. The resulting suspension was stirred at room
temperature for 3 h, and then the mixture was concentrated in
vacuo. The residue was dissolved in EtOAc, and sequentially
washed with 4% NaHCO3, 1 M HCl, and brine. The organic layer was
dried over Na2SO4 and concentrated in vacuo. The crude product
was purified by silica-gel column chromatography using hexane/
EtOAc as the eluent to give the desired N-acryloyl amino acid
methyl esters 2 as colorless liquids (83–90%).
2c. Colorless liquid, IR (KBr, cmÀ1) 3333, 2964, 1732, 1668; 1H
NMR (300 MHz, CDCl3) dH 0.17–0.21 (m, 6H), 1.21 (s, 3 H), 1.38–1.49
(m, 1H), 2.98 (s, 3H), 3.79–3.83 (m, 1H), 4.60 (s, 1H), 4.99 (s, 1H),
5.99–6.02 (br, 1H); 13C NMR (75 MHz, CDCl3) dC 17.1, 17.2, 17.3, 30.5,
51.2, 57.0, 119.4, 139.1, 167.9, 171.8; HRMS (FAB) calcd for (M + H)+
C10H18NO3: 200.1287, found 200.1291.
2d. White solid, mp 170 ꢀC; IR (KBr, cmÀ1) 3284, 3079, 2966,
1739, 1647, 1622; 1H NMR (300 MHz, CDCl3) dH 0.86–1.01 (m, 12H),
2.02–2.20 (m, 2H), 3.73 (s, 3H), 4.46–4.50 (m, 1H), 4.72–4.77 (m,
1H), 5.59 (dd, J = 9.4, 2.5 Hz, 1H), 6.19–6.39 (m, 2H), 7.55–7.58 (br,
1H), 7.81 (br, 1H); 13C NMR (75 MHz, CDCl3) dC 18.0, 18.3, 18.7, 19.0,
30.6, 31.4, 51.8, 57.5, 58.4, 126.5, 130. 8, 165.6, 172.0, 172.5; HRMS
(FAB) calcd for (M + H)+ C14H25N2O4: 285.1805, found 285.1810.
3a (mixture of diastereomers). White solid, mp 110–111 ꢀC; IR
(KBr, cmÀ1) 3341, 2970, 1747, 1679; 1H NMR (300 MHz, CDCl3) dH
0.87–0.98 (m, 12H), 1.44 (s, 9H), 1.52–1.92 (m, 4H), 2.25–2.35
(m, 2H), 3.39–3.64 (m, 1H), 3.72–3.73 (m, 3H), 4.48–4.57 (m, 1H),
6.52–6.62 (br, 1H), 6.99–7.02 (br, 1H); 13C NMR (75 MHz, CDCl3) dC
17.6, 17.7, 17.8, 18.9, 19.0, 28.3, 28.9, 29.0, 30,5, 30.9, 32.4, 33.2, 33.4,
51.9, 54.8, 55.1, 57. 1, 57.4, 79.1, 79.2, 156.4, 156.7,172.5,172.8,173.3;
HRMS (FAB) calcd for (M + H)+ C18H35N2O5: 359.2547, found
359.2545.
2.3. Synthesis of N-BocValValOH 6
EDC hydrochloride (1.2 equiv, 0.53 g) and HOBt (1.4 equiv,
0.49 g) were added to a solution of N-BocValOH (2.3 mmol, 0.50 g),
valine methyl ester hydrochloride (2.3 mmol, 0.69 g), and i-Pr2NEt
(1.2 equiv, 0.48 mL) in DMF (15 mL) at 0 ꢀC. The mixture was stirred
at 0 ꢀC for 2 h and then at room temperature for overnight. Then,
the mixture was concentrated in vacuo. The residue was dissolved
in CH2Cl2, and sequentially washed with 1 M HCl, 4% NaHCO3, and
water. The organic layer was dried over MgSO4 and concentrated in
vacuo. The crude product was purified by silica-gel column
chromatography using hexane/EtOAc as the eluent to give
N-BocValValOMe as a white solid (71%).
A MeOH solution (10 mL) of N-BocValValOMe (5.1 mmol, 1.69 g)
was added to 1 M NaOH (5.1 mL). The solution was stirred at room
temperature for 3 h. The pH of the mixture was decreased to 7 by
adding 1 M H2SO4 and the resulting solution was concentrated in
vacuo. The residue was dissolved in 5% NaHCO3 and washed with
EtOAc. The pH of the aqueous layer decreased to 2–3 with 1 M
H2SO4. The solution was extracted with EtOAc. The organic layer
was dried over MgSO4 and concentrated in vacuo. The crude
product was purified by silica-gel column chromatography using
hexane/EtOAc as the eluent to give the desired N-BocValValOH 6 as
a white solid (77%).
3b. Colorless liquid, IR (KBr, cmÀ1) 3326, 2969, 1742, 1694; 1H
NMR (300 MHz, CDCl3) dH 0.94 (t, J = 7.1 Hz, 6H), 1.44 (s, 9H),
1.77–1.86 (m, 2H), 2.13–2.24 (m, 1H), 2.26–2.31 (m, 2H), 3.12–3.27
(m, 2H), 3.73 (s, 3H), 4.51–4.59 (m, 1H), 4.79 (br, 1H), 6.60 (br, 1H);
13C NMR (75 MHz, CDCl3) dC 14.2, 17.7, 19.0, 26.5, 28.3, 31.0, 33.5,
39.6, 57.2, 61.1, 79.3, 156.4, 172.1, 172.7; HRMS (FAB) calcd for
(M + H)+ C15H298N2O5: 317.2077, found 317.2083.
3c (mixture of diastereomers). White solid, mp 115–116 ꢀC; IR
(KBr, cmÀ1) 3335, 2966, 1740, 1681; 1H NMR (300 MHz, CDCl3) dH
0.91–0.96 (m, 6H), 1.43 (s, 9H), 1.64–1.86 (m, 3H), 2.10–2.34 (m,
6H), 3.73 (m, 3H), 4.46–4.55 (m, 1H), 4.91–5.03 (br, 1H), 5.81 (br,
1H), 6.41 (br, 1H); 13C NMR (75 MHz, CDCl3) dC 17.7, 18.8, 19.0, 19.2,
28.2, 30.6, 30.9, 31.4, 31.5, 31.6, 31.7, 32.5, 32.6, 32.9, 49.9, 52.0, 57.1,
57.3, 79.3, 79.4, 156.5, 156.7, 172.7, 172.8, 172.9, 173.1, 175.5, 175.6;
HRMS (FAB) calcd for (M + H)+ C18H34N3O6: 388.2448, found
388.2473.
2.4. Photoreaction of 1 with 2
An aqueous CH3CN solution (CH3CN 90 mL, H2O 10 mL) of N-Boc
amino acid 1 (5 mM), N-acryloyl amino acid ester 2 (5 mM), Phen
(89.1 mg, 5 mM), and 1,3-DCB (64.0 mg, 5 mM) in Pyrex vessels
(18 mm  180 mm) was purged with Ar for 10 min. The mixture
was irradiated with 100 W high-pressure mercury lamp for 6 h. The
crude product was purified by silica-gel column chromatography
using hexane/EtOAc or CHCl3/acetone as the eluents to give adduct
3. The photoreaction of compound 6 was also performed similarly.
3d (mixture of diastereomers). White solid, mp 94 ꢀC; IR
(KBr, cmÀ1) 3338, 2958, 1745, 1680; 1H NMR (300 MHz, CDCl3) dH
0.92–0.97 (m, 6H), 1.44 (s, 9H), 1.56–1.98 (m, 5H), 2.06–2.17 (m,
3H), 2.24–2.36 (m, 2H), 2.44–2.69 (m, 2H), 3.58–3.90 (m, 4H),
4.48–4.59 (m, 1H); 13C NMR (75 MHz, CDCl3) dC 15.6,17.8, 19.0, 19.1,
28.3, 30.6, 30.7, 31.1, 31.8, 31.9, 33.0, 33.1, 35.5, 35.6, 49.7, 49.8, 52.0,
57.2, 57.4, 79.5, 156.1, 156.3, 172.5, 172.6, 173.0; HRMS (FAB) calcd
for (M + H)+ C18H35N2O5S: 391.2267, found 391.2260.

52
K. Osaka et al. / Journal of Photochemistry and Photobiology A: Chemistry 317 (2016) 50–55
Table 1
Decarboxylative radical addition of 1 to 2a by photoirradiation.a
Entry
1c
1
3
Yield of 3 (%)b
47
2
1a
1a
3a
3a
58
43
39
3d
4
5
6
7
61
26
48
8
9
34
35
10
25

K. Osaka et al. / Journal of Photochemistry and Photobiology A: Chemistry 317 (2016) 50–55
53
Table 1 (Continued)
Entry
1
3
Yield of 3 (%)b
11
23
a
Aqueous acetonitrile solution containing 1 (5 mM), 2a (5 mM), Phen (5 mM), 1,3-DCB (5 mM), and NaOH (5 mM) under an Ar atmosphere was irradiated for 6 h.
Isolated yield.
1 (20 mM), 2 (20 mM), Phen (20 mM), 1,4-DCB (20 mM), and NaOH (20 mM).
1 (5 mM), 2 (5 mM), Phen (3 mM), 1,3-DCB (3 mM), and NaOH (5 mM).
b
c
d
3e (mixture of diastereomers). Colorless liquid, IR (KBr, cmÀ1
)
13C NMR (125 MHz, CDCl3) dC 17.8, 19.0, 25.2, 31.3, 33.0, 52.2, 57.0,
66.7,114.5,114.9,120.8,129.5,129.7,158.8,172.4,172.6; HRMS (FAB)
calcd for (M + H)+ C16H24NO4: 294.1726, found 294.1715.
3301, 2969, 1744, 1683; 1H NMR (300 MHz, CDCl3) dH 0.96–0.98 (m,
6H),1.46 (s, 9H),1.62–2.52 (m, 9H), 3.30–3.34 (m, 2H), 3.75 (m, 3H),
3.88–4.20 (m, 1H), 4.49 (m, 1H); 13C NMR (125 MHz, CDCl3) dC 17.8,
17.9, 18.9, 19.1, 19.2, 23.1, 23.6, 28.5, 30.7, 33.6, 46.2, 46.5, 52.0, 56.0,
57.6, 57.7, 79.4, 79.5, 154.7, 155.5, 155.8, 172.5, 172.7, 172.9, 173.3,
173.8; HRMS (FAB) calcd for (M + H)+ C18H33N2O5: 357.2390, found
357.2373.
4. [22] White solid, mp 135–136 ꢀC; 1H NMR (300 MHz, CDCl3)
dH 0.84–0.93 (m, 6H), 1.40 (s, 9H), 1.93–1.97 (m, 1H), 4.46 (br, 1H),
4.93 (m, 1H), 7.33 (d, J = 8.1 Hz, 2H), 7.62 (d, J = 8.1 Hz, 2H); 13C NMR
(75 MHz, CDCl3) dC 18.2, 19.7, 28.4, 33.5, 60.4, 79.9, 110.8, 118.9,
127.6, 132.2, 147.9, 155.4.
3f. Colorless liquid, IR (KBr, cmÀ1) 3326, 2970, 1743, 1653; 1H
NMR (300 MHz, CDCl3) dH 0.94 (t, J = 7.1 Hz, 6H), 1.26 (s, 6H), 1.43 (s,
9H),1.92–2.16 (m, 3H), 2.27 (t, J = 8.1 Hz, 2H), 3.73 (s, 3H), 4.53–4.57
(m, 1H), 4.73 (br, 1H), 6.36 (br, 1H); 13C NMR (75 MHz, CDCl3) dC
14.0, 18.7, 20.8, 28.2, 31.0, 31.4, 35.9, 51.8, 51.9, 56.8, 60.2, 78.6,
154.5, 172.4, 173.1; HRMS (FAB) calcd for (M + H)+ C17H33N2O5:
345.2390, found 345.2401.
5a. White solid, mp 89–90 ꢀC; IR (KBr, cmÀ1) 3317, 2976, 1744,
1646; 1H NMR (300 MHz, CDCl3) dH 0.88–0.97 (m, 6H), 1.44 (s, 9H),
1.53–1.76 (m, 2H), 1.81–1.92 (m, 1H), 2.21–2.34 (m, 2H), 3.47–3.58
(m, 1H), 3.75 (s, 3H), 3.97–4.13 (m, 2H), 4.42–4.45 (m, 1H), 6.83 (br,
1H); 13C NMR (75 MHz, CDCl3) dC 17.7, 19.1, 28.4, 29.1, 32.6, 33.3,
41.3, 52.2, 55.0, 79.3, 156.7, 170.4, 173.4; HRMS (FAB) calcd for
(M + H)+ C15H29N2O5: 317.2077, found 317.2086.
3g. White solid, mp 53–54 ꢀC; IR (KBr, cmÀ1) 3298, 2924, 1746,
1647; 1H NMR (300 MHz, CDCl3) dH 0.88–0.92 (m, 6H), 1.07–1.30
(m, 5H), 1.50–1.78 (m, 8H), 2.09–2.27 (m, 3H), 3.74 (s, 3H), 4.56–
4.60 (m, 1H), 5.93 (br, 1H); 13C NMR (125 MHz, CDCl3) dC 17.9, 19.0,
26.3, 26.6, 31.4, 33.0, 33.1, 34.3, 37.3, 52.2, 56.8, 172.8, 173.4; HRMS
(FAB) calcd for (M + H)+ C15H28NO3: 270.2070, found 270.2058.
3h. Colorless liquid, IR (KBr, cmÀ1) 3299, 2901, 1746, 1647; 1H
NMR (300 MHz, CDCl3) dH 0.89–0.94 (m, 6H), 1.415–1.49 (m, 7H),
1.59–1.74 (m, 7H), 1.95 (m, 3H), 2.06–2.27 (m, 3H), 3.74 (s, 3H),
4.55–4.59 (m,1H), 5.92–5.95 (br,1H); 13C NMR (125 MHz, CDCl3) dC
17.9,19.0, 28.6, 30.4, 31.4, 32.0, 37.1, 39.8, 41.3, 42.1, 52.2, 56.8,172.9,
173.9; HRMS (FAB) calcd for (M + H)+ C19H32NO3: 322.2383, found
322.2386.
5b (mixture of diastereomers). White solid, mp 59–61 ꢀC; IR
(KBr, cmÀ1) 3285, 2970, 1750, 1650; 1H NMR (300 MHz, CDCl3) dH
0.85–1.02 (m, 12H), 1.12–1.21 (m, 3H), 1.46 (s, 9H), 1.52-2.42 (m,
5H), 3.45-3.53 (m, 1H), 3.72 (m, 3H), 4.39–4.46 (m, 1H), 4.52–4.58
(m, 1H), 6.02–6.09 (br, 1H); 13C NMR (75 MHz, CDCl3) dC 17.6, 17.8,
17.9, 18.0, 18.6, 18.7, 18.8, 19.0, 19.1, 19.2, 28.3, 30.8, 31.2, 31.4, 32.5,
32.9, 33.1, 35.4, 37.6, 38.4, 38.6, 39.5, 51.8, 52.1, 53.7, 54.0, 54.2, 56.8,
56.9, 57.5, 60.3, 78.9, 79.0, 79.5, 156.0, 156.9, 172.6, 172.7, 172.7,
176.0, 176.7, 176.8; HRMS (FAB) calcd for (M + H)+ C19H37N2O5:
373.2703, found 373.2675.
5c (mixture of diastereomers). White solid, mp 142–144 ꢀC; IR
(KBr, cmÀ1) 3292, 2964, 1747, 1639; 1H NMR (300 MHz, CDCl3) dH
0.87–0.98 (m, 18H), 1.44 (s, 9H), 1.55–1.77 (m, 2H), 2.08–2.21 (m,
2H), 2.23–2.38 (m, 2H), 3.39–3.53 (m, 1H), 3.73 (s, 3H), 4.38–4.67
(m, 3H); 13C NMR (75 MHz, CDCl3) dC 17.7, 17.8, 17.9, 18.1, 18.3, 18.8,
18.9,19.0, 19.1, 19.2, 28.3, 29.0, 29.1, 30.5, 30.9, 32.4, 32.6, 33.5, 51.9,
52.0, 54.9, 55.0, 57.0, 57.1, 58.4, 58.6, 79.0, 79.2, 156.4, 156.7, 171.4,
3i. Colorless liquid, IR (KBr, cmÀ1) 3309, 3040, 2964, 1743, 1652;
1H NMR (300 MHz, CDCl3) dH 0.86–0.92 (m, 6H), 2.08–2.18 (m, 3H),
2.47 (t, J = 7.4 Hz, 2H), 3.71 (s, 3H), 4.02 (t, J = 5.6 Hz, 2H), 4.55–4.59
(m, 1H), 6.03–6.06 (br, 1H), 6.84–6.97 (m, 3H), 7.21–7.33 (m, 2H);

54
K. Osaka et al. / Journal of Photochemistry and Photobiology A: Chemistry 317 (2016) 50–55
Table 2
Decarboxylative radical addition of 1a to 2b–d by photoirradiation.a
Entry
1
2
5
Yield of 5 (%)b
39
2
3
36
45
a
Aqueous acetonitrile solution containing 1a (5 mM), 2 (5 mM), Phen (5 mM), 1,3-DCB (5 mM), and NaOH (5 mM) under an Ar atmosphere was irradiated for 6 h.
Isolated yield.
b
171.5,172.1,173.1,173.2; HRMS (FAB) calcd for (M + H)+ C23H44N3O6:
458.3231, found 458.3205.
at room temperature to produce the decarboxylative radical
adduct 3a in a moderate yield (47%) as a 1:1 mixture of
diastereomers along with the formation of substituted product 4
(17%) and polymeric materials. In contrast to the previous results
obtained when acrylonitrile was used as a radical acceptor [11,16],
the use of the relatively poorly electron-deficient alkenes such as
2a instead of acrylonitrile led to significantly low rate of radical
addition of the generated radical to 2a. This promoted radical
7 (mixture of diastereomers). White solid, mp 110–111 ꢀC; IR
(KBr, cmÀ1) 3297, 2964, 1747, 1646; 1H NMR (300 MHz, CDCl3) dH
0.87–1.01 (m, 24H), 1.44 (s, 9H), 1.91–2.21 (m, 6H), 3.31–3.75 (m,
4H), 3.76–4.58 (m, 3H), 6.35–6.60 (br, 1H); 13C NMR (75 MHz,
CDCl3) dC 17.9, 18.0, 18.1, 18.2, 18.4, 18.6, 18.7, 18.9, 19.0, 19.1, 19.3,
19.4, 19.5, 27.6, 28.3, 30.1, 30.5, 30.7, 30.8, 30.9, 31.1, 31.7, 32.3, 32.9,
52.0, 52.1, 54.0, 57.2, 57.3, 59.2, 59.3, 60.3, 79.8, 156.4, 171.9, 172.2,
172.5, 172.6, 172.7, 173.3, 173.6; HRMS (FAB) calcd for (M + H)+
C28H53N4O7: 557.3915, found 557.3914.
addition to the radical anion of 1,4-DCB, affording
4 via
decyanation as reported by us [10]. In order to avoid this
photosubstitution, the use of 1,3-dicyanobenzene (1,3-DCB)
instead of 1,4-DCB led to no formation of the corresponding
substitution product. Moreover, a low concentration of 2a (5 mM)
suppressed the polymerization and slightly increased the yield of
3a (58%, Entry 2). In this photoreaction, catalytic amounts of Phen
(3 mM) and 1,3-DCB (3 mM) also worked (Entry 3). When other
3. Results and discussion
Initially, the photoinduced decarboxylative radical addition of
N-Boc
L-valine 1a (Boc = tert-butoxycarbonyl) to N-acryloyl
L-valine
methyl ester 2a was examined because
obtained by the photoreaction (Table 1). Photoreaction of 1a
(20 mM) was carried out by irradiating (100 W high-pressure
g
- and -dipeptide 3a was
a
N-Boc
similar decarboxylative radical addition with 2a successfully
underwent to produce - and -dipeptides 3b–f (Entries 4–8).
a-amino acids 1b–f were subjected to photoreaction, the
g
a
mercury lamp through a Pyrex glass filter;
acetonitrile solutions (CH3CN/H2O = 9:1, v/v) containing Phen
(20 mM), 1,4-DCB (20 mM) and 2a (20 mM) under argon for 6 h
g
> 280 nm) aqueous
In addition, the use of other simple carboxylic acids such as
cyclohexanecarboxylic acid 1 g, 1-adamantanecarboxylic acid 1h,
and phenoxyacetic acid 1i also yielded the corresponding
Scheme 2. Formation of tetrapeptide 7 by the photoreaction of 6 and 2d.

K. Osaka et al. / Journal of Photochemistry and Photobiology A: Chemistry 317 (2016) 50–55
55
decarboxylative radical adducts 3g–i (Entries 9–11). Thus, a variety
Appendix A. Supplementary data
of unique N-alkylcarbonyl amino acid derivatives 3 could be
directly synthesized from carboxylic acids 1 and 2a under mild
reaction conditions, and, in particular, the photoreaction of
Supplementary data associated with this article can be found, in
the online version, at http://dx.doi.org/10.1016/j.jphotochem.2015.
11.001.
a
-amino acids afforded the corresponding
g- and a-dipeptides.
To demonstrate the utility of this methodology, the photo-
reactions of other N-acryloyl amino acid methyl esters 2b–d such
as glycine 2b,N-methacrylic valine 2c, and dipeptide derivatives 2d
were investigated (Table 2). Dipeptides 5a,b and tripeptide 5c were
also obtained in moderate yields. Finally, tetrapeptide 7 was
obtained from the photoreaction of dipeptides 6 and 2d under the
same photochemical conditions, even though the low solubility of
adduct 7 in this solution decreased the yield of 7 (20%, Scheme 2).
Notably, the photoreactions of peptides and N-acryloyl peptides
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g
-amino acids via decarboxylation when 2 was used with N-Boc
amino acids 1 and peptides 6. The applications of this photoreac-
tion to the modification and coupling of peptide are underway.
Supplementary material
The 1H and 13C NMR spectra of 2c–d, 3, 4, 5, and 7 are provided
in Supplementary material.