Photochemical and Additive-Free Coupling Reaction of α-Cumyl α-Keto Esters via Intermolecular C-H Bond Activation

Article abstract of DOI:10.1055/s-0035-1561098

We developed a photo-chemical coupling reaction of α-keto esters with several simple alcohols, alkanes, ethers, and amides. Use of tertiary alkyl ester, α-cumyl ester, is the key for avoiding the known photo-degradation process. Intermolecular C-H bond ac

Full text of DOI:10.1055/s-0035-1561098

SYNLETT
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© Georg Thieme Verlag Stuttgart · New York
2016, 27, 1128–1132
letter
1128
E. Ota et al.
Letter
Synlett
Photochemical and Additive-Free Coupling Reaction of α-Cumyl
α-Keto Esters via Intermolecular C–H Bond Activation
Eisuke Otaa,b
Yu Mikamea,c
Go Hirai*a,d,e
Shigeru Nishiyamab
Mikiko Sodeoka*a,d,e
R1
H
O
R1
hν
OH
O
OCMe2Ph
16 examples
R = Et, i-Pr, t-Bu, Ph
R
R
31–85%
O
O
O
α-cumyl (CMe2Ph)
H
H
R3
O
H
a Synthetic Organic Chemistry Laboratory, RIKEN, 2-1 Hirosawa,
Wako, Saitama, 351-0198, Japan
b Faculty of Science and Technology, Keio University, 3-14-1
Hiyoshi, Kohoku-ku, Yokohama, Kanagawa, 223-8522, Japan
c Department of Life Science and Biotechnology, Tokyo University
of Agriculture and Technology, 2-24-16, Naka-cho, Koganei,
Tokyo, 184-8588, Japan
d RIKEN Center for Sustainable Resource Science, 2-1 Hirosawa,
Wako, Saitama, 351-0198, Japan
e AMED-CREST, 2-1 Hirosawa, Wako, Saitama, 351-0198, Japan
gohirai@riken.jp
R5
O
O
H
H
Ph
R3 = t-Bu, Ph
c-Pentyl
O
H
N
R4
H
=
R1
R2
OH
NH
H
N
R4 = H, Me
R2 = H, n-Pr
R5 = H, NHBoc
H
O
ethers
H
alcohols
alkanes
amides
sodeoka@riken.jp
Received: 26.11.2015
Accepted after revision: 14.12.2015
Published online: 04.01.2016
Photoreaction of α-dicarbonyl systems such as 1,2-dike-
tones and α-keto amides, especially to construct four-mem-
bered rings (Norrish–Yang cyclization), has often been uti-
lized in the synthesis of complex molecules,1–3 because an
sp3 C–H bond is directly functionalized without introduc-
tion of a reactive group.4 However, photo-induced C–C
bond formation of the keto group in α-keto esters (1 or 8) is
less predictable. In contrast to 1,2-diketones or α-keto am-
ides, β-lactone 7 formation has never been reported
(Scheme 1,A). Photoexcitation of the keto group of 1 (n–π*
transition, 2) is possible by irradiation at long wavelength
(more than 350 nm). Subsequent [1,5] H-atom shift (Nor-
rish-type II reaction) would generate a putative 1,4-diradi-
cal species 3, as with other α-dicarbonyls. However, cycliza-
tion of 3 to form 7 appears to be disfavored. Instead, reduc-
tive dimerization from 2 to provide 45,6 or degradation from
3 to 5 and 6 (Norrish-type II fragmentation)7,8 occurs pref-
erentially (Scheme 1,A).9
DOI: 10.1055/s-0035-1561098; Art ID: st-2015-u0918-l
Abstract We developed a photo-chemical coupling reaction of α-keto
esters with several simple alcohols, alkanes, ethers, and amides. Use of
tertiary alkyl ester, α-cumyl ester, is the key for avoiding the known
photo-degradation process. Intermolecular C–H bond activation and
subsequent C–C bond formation were promoted by irradiation with an
LED lamp (365 nm) without any additives. Among the coupling part-
ners, reactions with sterically less demanding amides proceeded effi-
ciently to provide unique N-acyl-β-amino-α-hydroxy acid derivatives. In
benzene or acetone as a solvent, the reaction with a solid amino acid
derivative provided a precursor of tetrahydro-1,4-diazepine-2,5-dione
derivatives.
Key words photo-chemical reaction, α-keto esters, coupling reac-
tions, C–H bond activation, β-amino acid derivatives, α-cumyl esters,
tetrahydro-1,4-diazepine-2.5-dione
A)
OH
R1
O
R1
O
R1
O
O
O
R1
H
R2
R2
HO R1
C)
HO
R3
H
R2
hν
5
no Nα-proton
O
HO
R3
R3
O
H
O
O
O
R2
R2
R3
R2
O
H
or
+
O
R3
N
Ph
Ph
R3
O
1,5-H
atom
shift
R3
HO
O
O
2
O
3
6
O
R1
O
Ph
7
R1
R2
1
11
4
MeOH
or
fragmentation
dimerization
hν
2-BuOH
B)
OH
OH
H
H
OH
H
O
O
OH
OH
or
OR
hν
n
O
N
Ph
Ph
R
n
or
or
OR
O
OR
O
R
R
O
O
O
Ph
n = 5, 7, 8
n = 5, 7, 9, 10
O
O
O
O
8
9
10
12
Scheme 1 A) Representative photo-reaction of α-keto esters 1. B) Intra- or intermolecular photo-induced C–C bond formation of α-keto esters 8 via
C–H bond activation. C) Our recent work: Novel photo-induced cyclopropanol formation from α-keto amides 11 via C–H bond activation.
© Georg Thieme Verlag Stuttgart · New York — Synlett 2016, 27, 1128–1132

1129
E. Ota et al.
Letter
Synlett
On the other hand, some specific examples of intramo-
lecular C–C bond formation for α-keto esters such as 8,
bearing a C–H bond in close proximity to a keto group, have
been reported.10 As shown in Scheme 1 (B), C–C bond for-
mation would proceed via diradical species 9, which would
be generated by H-atom abstraction from the neighboring
C–H bond in a diradical species like 2 prior to degradation.
These precedents suggest the potential utility of photo-in-
duced coupling of α-keto esters, but only a few examples of
intermolecular photochemical coupling of α-keto esters via
C–H bond activation have been reported, and they are lim-
ited to specific substrates11 (methyl, ethyl, or allyl α-keto
ester) and reactants such as cyclohexene,12 HMPA,13 or a
4H-pyran derivative.14 The scope of photo-induced C–C
bond-forming coupling reaction of α-keto esters remains
unclear. Herein, we report photo-coupling reactions of
α-keto esters with alcohol, ether, alkanes, and amides.
We recently found a novel type of photoreaction of
bulky α-keto amides 11 without Nα protons, which should
not undergo Norrish-type II reaction, providing cyclopro-
panol 12 (Scheme 1,C).15 This result prompted us to investi-
gate the photoreaction of α-keto ester 13a with α-cumyl es-
ter, instead of trityl ester.16 We initially assumed that simi-
lar cyclopropanol formation from 13a might proceed, at
least to some degree, but the expected reaction did not oc-
cur. Instead, interestingly, irradiation of 13a with an LED
lamp (365 nm) produced the methanol adduct 14a in rea-
sonably good yield (Table 1, entry 1).17 This result indicates
that, unlike α-keto amides, avoiding the Norrish-type II
process allows intermolecular H-atom abstraction followed
by C–C bond formation to occur in the case of α-keto esters.
Indeed, in contrast to the reaction of 13a, irradiation of
α-keto esters 13b and 13c with primary or secondary alkyl
ester substituents, rapidly afforded messy mixtures, includ-
ing small amounts of methanol adducts 14b and 14c. In
both cases, the corresponding dimers 15b or 15c were de-
tected by MS analysis of the mixtures.
Next, we investigated the scope of the keto substituent.
Photolysis of phenyl derivative 13d in methanol gave the
corresponding adduct 14d in 25% yield. A complex mixture
was formed from thienyl derivative 13e, and the adduct 14e
was not detected. Photoreaction of isopropyl derivative 13f
proceeded smoothly to give 14f in 68% yield, whereas ethyl
derivative 13g gave 14g in lower yield (15%) with partial re-
covery of 13g (23%). Thus, a tertiary or secondary alkyl
group appears to be better as a keto substituent in the case
of the photochemical coupling reaction with alcohols.
We next investigated the photo-reaction of α-keto ester
13f with various coupling partners (Scheme 2). Photolysis
in 1-butanol provided the corresponding diol 16f in 33%
yield (d.r. = 1.6:1). In this case, dimer 15f was produced in
52% yield, together with a trace (5%) of α-hydroxy ester 17f,
which would be formed by disproportionation of the inter-
mediate radical species.18 With 2-propanol as a coupling
partner, adduct 18f was formed in only 8% yield. Instead, di-
mer 15f was the major product (64%) along with α-hydroxy
ester 17f (5%).
Coupling of 13f with toluene (bond-dissociation energy,
BDE: 89.7 kcal/mol)19 produced 19f in moderate yield. It
was found that coupling proceeded even with cyclohexane
(BDE: 99.5 kcal/mol)19 to provide 20f (40%), along with 15f
and 17f.
Then, we examined the reaction with ethers commonly
used as solvents, in the expectation that Oα–C–H bond acti-
vation would be accelerated by electron transfer from the
O atom (Scheme 2,B).20 As we expected, photolysis of 13f in
t-BuOMe provided the unique tertiary alcohol derivative
21f in good yield (73%). Coupling with anisole or 1,4-diox-
Table 1 Photo-Induced Coupling of α-Keto Esters 13 with Methanol
OH
R4
R4
CO2R5
OH
O
hν
OH
R4
CO2R5
CO2R5
R4
CO2R5
14
MeOH
(80 mM)
OH
15
13
Entry
Substrate
R4
t-Bu
R5
Time
4 h
Product 14
Yield (%)
1
2
3
4
5
6
7
13a
13b
13c
13d
13e
13f
C(CH3)2Ph
14a
14b
14c
14d
14e
14f
54
t-Bu
t-Bu
Ph
CH2CH2Ph
CH(CH3)Pha
C(CH3)2Ph
C(CH3)2Ph
C(CH3)2Ph
C(CH3)2Ph
20 min
5 min
1 h
3
10 (d.r. = 1:1)
25
0
thienyl
i-Pr
1 h
3 h
68
15b
13g
Et
1 h
14g
a (R)-phenethyl ester was used.
b 23% recovery of the starting material 13g.
© Georg Thieme Verlag Stuttgart · New York — Synlett 2016, 27, 1128–1132

1130
E. Ota et al.
Letter
Synlett
ane similarly afforded 22f and 23f in reasonable yields.
When the reaction was carried out in cyclopentylmethyle-
ther (CPME), formation of 15f and 17f also occurred, and
coupling product 24f, which is formed by H-atom abstrac-
tion from the less hindered methyl group followed by C–C
bond formation, was obtained in only 23% yield. The results
of the photoreactions with CPME and i-PrOH indicated that
photocoupling with an Oα-methine group is disfavored,
probably for steric and/or electronic reasons, allowing di-
merization and disproportionation reactions to occur in
competition with photocoupling. Comparison of the reac-
tions with t-BuOMe and anisole suggested that BDE is un-
likely to be the dominant factor for the coupling reaction
(BDE; CH3OCH2–H: 96.1 kcal/mol, PhOCH2–H: 92.0
kcal/mol).19 In case of heteroatom-containing coupling
partners, an electron-transfer process may also contribute
to this coupling reaction.
cantly contributes to the reaction, the NαC–H bond should
be preferentially activated over the C–H bond of the acetyl
group, despite its higher BDE [BDE; HCON(CH2–H)2: 105
kcal/mol, H–CH2CONMe2: 91.0 kcal/mol].19 As expected,
photolysis of 13f in N,N-dimethylacetamide cleanly and se-
lectively afforded 25f in excellent yield (85%); this rep-
resents a direct synthesis of a β-amino-α-hydroxy acid de-
rivative containing a tetrasubstituted α-carbon center.21
Coupling reactions of phenyl or ethyl derivative 13d and
13g also successfully proceeded to give 25d and 25g in
good yields. N-Methylacetamide also afforded the adduct
26f in 84% yield. With cyclic 2-pyrrolidone, H-atom abstrac-
tion and C–C bond formation occurred to provide 26f in
31% yield, indicating that coupling reaction with the Nα-
methylene group was possible, as well as at the Oα-position
(like 23f). In the case of the reaction with N-methylpyrroli-
done, the coupling products were formed in 78% total yield.
The regioisomer 28f, the coupling product at the Nα-meth-
ylene group, was formed preferentially (57% yield,
Therefore we next examined the reaction of N,N-di-
methylacetamide. If the electron-transfer process signifi-
CMe2Ph
O
(A)
HO
O
R
OH
O
hν
OCMe2Ph
OCMe2Ph
OH
OCMe2Ph
O
R4
R4
OCMe2Ph
R-H
O
(solvent, 80 mM)
HO
13d: R4 = Ph; 13f: R4 = i-Pr
13g: R4 = Et
O
O
15f
17f
Alcohols
Alkanes
OH
Ph
OH
OH
OH
OH
O
OH
O
HO
HO
OCMe2Ph
OCMe2Ph
OCMe2Ph
OCMe2Ph
OCMe2Ph
O
O
O
14f: 68% (3 h)
16f: 33%a (20 min, d.r. = 1.6:1)
18f: 8%b (1 h)
19f: 38% (1 h)
20f: 40%c (1 h)
(in methanol)
(in 1-butanol)
(in 2-propanol)
(in toluene)
(in cyclohexane)
Ethers
Ph
O
O
O
O
OH
OH
O
OH
OH
O
OCMe2Ph
OCMe2Ph
OCMe2Ph
OCMe2Ph
O
O
O
21f: 73% (15 min)
(in t-BuOMe)
22f: 40% (70 min)
(in anisole)
23f: 50% (20 min, d.r. = 1:1)
24f: 23%d (10 min)
(in cyclopentylmethylether)
(in 1,4-dioxane)
O
O
Amides
NH
O
O
O
N
H
N
N
N
OH
OH
OH
OH
OH
O
+
OCMe2Ph
OCMe2Ph
OCMe2Ph
OCMe2Ph
OCMe2Ph
R4
O
O
O
O
R4 = i-Pr (25f): 85% (10 min)
4 = Ph (25d): 55% (5 min)
4 = Et (25g): 52% (40 min)
(in N,N-dimethylacetamide)
26f: 84% (35 min)
(in N-methylacetamide)
27f: 31% (10 min, d.r. = 1:1)
28f: 57% (d.r. = 1:1)
(in N-methylpyrrolidone, 10 min)
29f: 21%
R
R
(in 2-pyrrolidone)
X
(B)
O
OH
electron
transfer
O
proton
H
C–C bond
formation
HO
transfer
+
X
O
O
O
O
+
+
X
X
electron
H
O
O
O
reorganization
O
Scheme 2 (A) Photo-induced coupling reactions of α-keto esters 13. (B) Plausible mechanism of coupling reaction via an electron transfer process.
Isolated yields are shown unless otherwise noted: a) 15f (52%, calcd yield) and 17f (5%, calcd yield) were obtained; b) 15f (64% calcd yield) and 17f (5%
calcd yield) were obtained; c) 15f (20%, calcd yield) and 17f (8%) were obtained; d) 15f (20%) and 17f (19%) were obtained.
© Georg Thieme Verlag Stuttgart · New York — Synlett 2016, 27, 1128–1132

1131
E. Ota et al.
Letter
Synlett
d.r. = 1:1), and the coupling product at the methyl group
29f was also obtained (21% yield).
coupling partners of α-keto esters, enabling rapid access to
β-amino-α-hydroxyacid derivatives. Our method does not
require additives28 and is operationally simple. Further ap-
plications are being examined.
We also tried photolysis of 13f in actetone, benzene,
t-BuOH, MeCN, t-BuOAc, and CF3Ph, but no coupling prod-
uct with these molecules was detected. Instead, only degra-
dation of 13f was observed. We found that the degradation
rates of 13f in acetone and benzene were slower than those
in t-BuOH, MeCN, t-BuOAc, and CF3Ph.22 In using reactive
amide substrates as a coupling partner, the reaction can be
diluted with acetone or benzene (Scheme 3,A). Irradiation
of 13f in the presence of 50, 15, and even 5 equivalents of
N,N-dimethylacetamide in benzene successfully afforded
the coupling product 25f in good yields.23
Acknowledgment
We would like to thank Prof. Kazuo Nagasawa (Tokyo University of
Agriculture and Technology, Japan) and Prof. Kazunobu Toshima (Keio
University, Japan) for their support. This work was partially funded by
a Grant-in-Aid for Scientific Research (No.26102744). E.O. is a Re-
search Fellow of JSPS.
Supporting Information
hν
(A)
N,N-dimethylacetamide (X equiv)
X = 50: 87%
X = 15: 83%
X = 5: 67%
Supporting information for this article is available online at
http://dx.doi.org/10.1055/s-0035-1561098.
13f
25f
benzene
(80 mM)
S
u
p
p
o
nrtIo
g
f
rmoaitn
S
u
p
p
ortiInfogrmoaitn
NHBoc
(B)
References and Notes
N
hν
O
N
BocHN
30 (15 equiv)
∗
(1) (a) Wagner, P. J. In Synthetic Organic Photochemistry; Griesbeck,
A. G.; Mattay, J., Eds.; Marcel Dekker: New York, 2005, 11–39.
(b) Wessig, P.; Mühling, O. In Synthetic Organic Photochemistry;
Griesbeck, A. G.; Mattay, J., Eds.; Marcel Dekker: New York,
2005, 40–87.
13f
OH
O
HO
O
acetone
(80 mM)
OCMe2Ph
OCMe2Ph
∗
O
O
31: 58%
32
BocHN
N
(2) (a) Henery-Logan, K. R.; Chen, C. G. Tetrahedron Lett. 1973, 14,
1103. (b) Kamijo, S.; Hoshikawa, T.; Inoue, M. Tetrahedron Lett.
2010, 51, 872. (c) Yoshioka, S.; Nagatomo, M.; Inoue, M. Org.
Lett. 2015, 17, 90.
(3) A selected review on photoreaction in organic synthesis:
Hoffmann, N. Chem. Rev. 2008, 108, 1052.
1) TFA–CH2Cl2
(3:1)
O
30
N
2
HO
5
2) HBTU, Et3N
toluene, 4 Å MS
reflux
N
H
O
33
49% (2 steps)
(4) Selected reviews on direct sp3 C–H bond functionalization, see:
(a) Liu, C.; Zhang, H.; Shi, W.; Lei, A. Chem. Rev. 2011, 111, 1780.
(b) Yamaguchi, J.; Yamaguchi, A. D.; Itami, K. Angew. Chem. Int.
Ed. 2012, 51, 8960. (c) Rouquet, G.; Chatani, N. Angew. Chem. Int.
Ed. 2013, 52, 11726. (d) Girard, S. A.; Knauber, T.; Li, C.-J. Angew.
Chem. Int. Ed. 2014, 53, 74.
(5) Yang, N. C.; Morduchowitz, A. J. Org. Chem. 1964, 29, 1654.
(6) Another type of photo-induced dimerization catalyzed by cobal-
oxime: Kijima, M.; Miyamori, K.; Sato, T. J. Org. Chem. 1988, 53,
1719.
(7) (a) Huyser, E. S.; Neckers, D. C. J. Org. Chem. 1964, 29, 276.
(b) Obkircher, M.; Seufert, W.; Giese, B. Synlett 2005, 1182.
(8) Another type of degradation: (a) Hammond, G. S.; Leermakers,
P. A.; Turro, N. J. J. Am. Chem. Soc. 1961, 83, 2395.
(b) Leermakers, P. A.; Warren, P. C.; Vesley, G. F. J. Am. Chem. Soc.
1964, 86, 1768.
Scheme 3 A) Coupling reactions of α-keto esters 13f in diluted N,N-
dimethylamide with benzene. B) Reaction with the glycine derivative 30
and transformation of the major product into compound 33.
The use of solvent permits us to carry out reactions
with solid substrates such as N-Boc-protected glycinedime-
thylamide 30 (Scheme 3,B). The photoadduct 31 was ob-
tained in 58% yield as the major product of photolysis of 13f
in the presence of 30 (15 equiv) in acetone.24 It should be
noted that only a trace amount of regioisomer 32 was de-
tected, although radical species at the Nα-methylene group
next to the carbonyl group in 30 should be also stabilized
by captodative effect.25
The α-cumyl group is labile under mild acidic condi-
tions,26 and the Boc and α-cumyl groups in 31 were re-
moved simultaneously to generate the amino acid deriva-
tive. Treatment of the crude material under condensation
reaction conditions at elevated temperature afforded the
biologically intriguing tetrahydro-1,4-diazepine-2.5-dione
(homodiketopiperazine) derivative 33 containing a tetra-
substituted carbon center.27
In conclusion, we have achieved photoinduced coupling
of α-keto esters by utilizing bulky α-cumyl esters. This reac-
tion expands the synthetic utility of α-keto esters as build-
ing blocks. N,N-Dimethylamides were found to be excellent
(9) Some photo-induced [2+2] cycloadditions of α-keto esters have
been reported. Representative examples: (a) Nehrings, A.;
Scharf, H. D.; Runsink, J. Angew. Chem., Int. Ed. Engl. 1985, 97,
882. (b) Kato, N.; Takeshita, H. Bull. Chem. Soc. Jpn. 1985, 58,
1574. (c) Tian, G. R.; Mori, A.; Kato, N.; Takeshita, H. Bull. Chem.
Soc. Jpn. 1989, 62, 506. (d) Hatsui, T.; Nojima, C.; Takeshita, H.
Bull. Chem. Soc. Jpn. 1990, 63, 1611. (e) Hatsui, T.; Wang, J.-J.;
Takeshita, H. Bull. Chem. Soc. Jpn. 1994, 67, 2507.
(10) Representative examples for photo-induced ‘intramolecular’
cyclization of α-keto esters via C–H bond activation: (a) Pappas,
S. P.; Pappas, B. C.; Backwell, J. E. Jr. J. Org. Chem. 1967, 32, 3066.
(b) Gramain, J. C.; Remuson, R.; Vallee, D. J. Org. Chem. 1985, 50,
710. (c) Corey, E. J.; Gavai, A. V. Tetrahedron Lett. 1989, 30, 6959.
© Georg Thieme Verlag Stuttgart · New York — Synlett 2016, 27, 1128–1132

1132
E. Ota et al.
Letter
Synlett
(d) Gramain, J. C.; Remuson, R.; Vallee-Goyet, D.; Guilhem, J.;
Lavaud, C. J. Nat. Prod. 1991, 54, 1062. (e) Kraus, G. A.; Wu, Y. J.
Am. Chem. Soc. 1992, 114, 8705. (f) Hu, S.; Neckers, D. C. J. Chem.
Soc., Perkin Trans. 2 1997, 1751. (g) Hu, S.; Neckers, D. C. Tetrahe-
dron 1997, 53, 2751. (h) Hu, S.; Neckers, D. C. Tetrahedron 1997,
53, 7165.
(18) Kamijo, S.; Tao, K.; Takao, G.; Tonoda, H.; Murafuji, T. Org. Lett.
2015, 17, 3326.
(19) BDEs of C–H Bonds, In Comprehensive Handbook of Chemical
Bond Energies; CRC Press: Boca Raton, 2007, 19–145.
(20) Cho, D. W.; Yoon, U. C.; Mariano, P. S. Acc. Chem. Res. 2011, 44,
204.
(11) (a) Reaction of
a
specific bulky α-keto ester with
(21) Representative recent examples for the preparation of N-acyl-β-
methanol:Nakadaira, Y.; Hirota, Y.; Nakanishi, K. J. Chem. Soc.,
Chem. Commun. 1969, 1469. Decarboxylative coupling of α-keto
esters and low reactivity with 1,3-dithiane: (b) Tan, S. B.;
Shvydkiv, O.; Fiedler, J.; Hatoum, F.; Nolan, K.; Olegemoller, M.
Synlett 2010, 2240.
amino-α-hydroxy acid derivatives with a tetrasubstituted
carbon center: (a) Cai, A.-J.; Zheng, Y.; Ma, J.-A. Chem. Commun.
2015, 51, 8946. (b) Greco, A.; Tani, S.; De Marco, R.; Gentilucci, L.
Chem. Eur. J. 2014, 20, 13390. (c) Trost, B. M.; Malhotra, S.;
Ellerbrock, P. Org. Lett. 2013, 15, 440.
(12) Jolly, P. W.; de Mayo, P. Can. J. Chem. 1964, 42, 170.
(13) Kohmoto, S.; Kreher, T.; Yamamoto, M.; Yamada, K. Bull. Chem.
Soc. Jpn. 1990, 63, 3698.
(22) Recovery of 13f after irradiation for 1 h: 77% (in acetone), 80%
(in benzene), 69% (in t-BuOH), 54% (in MeCN), 44% (in t-BuOAc),
and 59% (in CF3Ph).
(14) Saleur, D.; Bouillon, J. P.; Portella, C.; Hoffmann, N. Tetrahedron
Lett. 2000, 41, 5199.
(23) Formation of the dimer 15f was also observed (X = 5, 15%;
X = 15, 15%; X = 50, 8%).
(15) Ota, E.; Mikame, Y.; Hirai, G.; Nishiyama, S.; Sodeoka, M. Tetra-
hedron Lett. 2015, 56, 5991.
(16) Trityl ester was prone to be hydrolyzed.
(24) Compound 30 was insoluble in benzene.
(25) Viehe, H. G.; Janousek, Z.; Merenyi, R.; Stella, L. Acc. Chem. Res.
1985, 18, 148.
(17) Typical Experimental Procedure for the Synthesis of 14f
A degassed 80 mM solution of 13f in MeOH (700 μL) was irradi-
ated with a 365 nm LED lamp until the starting material was
consumed (3 h for 13f). Silica gel column chromatography gave
14f (10.2 mg, 68%) as a colorless oil. 1H NMR (400 MHz, CDCl3):
δ = 0.88 (d, J = 6.9 Hz, 3 H), 0.94 (d, J = 6.9 Hz, 3 H), 1.81 (s, 3 H),
1.86 (s, 3 H), 2.06 (sept, J = 6.9 Hz, 1 H), 2.06 (m, 1 H), 3.40 (br d,
J = 1.8 Hz, 1 H) 3.76 (d, J = 11.0 Hz, 1 H), 3.88 (br m, 1 H), 7.27
(m, 1 H), 7.32–7.37 (m, 2 H), 7.40–7.43 (m, 2 H). 13C NMR (100
MHz, CDCl3): δ = 16.5, 17.2, 27.9, 28.9, 32.7, 66.7, 80.9, 84.3,
124.6 (2 C), 127.6, 128.4 (2 C), 144.8, 174.4. IR: 3485, 2969,
1727, 1270, 1225, 1134, 1102, 1077, 1031 cm–1. ESI-HRMS: m/z
[M + Na]+ calcd for C15H22NaO4: 289.1416; found: 289.1412.
(26) The α-cumyl group in 14f was easily removed by using 2% TFA
in the presence of i-Pr3SiH. See Supporting Information.
(27) No tetrahydro-1,4-diazepine-2.5-dione derivative with this
substitution pattern has been reported. For similar examples,
see: (a) Stoeckel-Maschek, A.; Stiebitz, B.; Koelsch, R.; Neubert,
K. Bioorg. Med. Chem. 2005, 13, 4806. (b) Jimenez-Gonzalez, E.;
Avila-Ortiz, C. G.; Gonzalez-Olvera, R.; Vargas-Caporali, J.;
Dewynter, G.; Juaristi, E. Tetrahedron 2012, 68, 9842.
(28) Photo-induced alkylation of α-keto esters promoted by forma-
tion of boron-enolate or adding benzimidazolines as an elec-
tron-transfer reagent has been reported: (a) Okada, K.; Hosoda,
Y.; Oda, M. J. Am. Chem. Soc. 1986, 108, 321. (b) Igarashi, T.;
Tayama, E.; Iwamoto, H.; Hasegawa, E. Tetrahedron Lett. 2013,
54, 6874.
© Georg Thieme Verlag Stuttgart · New York — Synlett 2016, 27, 1128–1132