Photodecarboxylative additions of α-thioalkyl-substituted carboxylates to alkyl phenylglyoxylates

Article abstract of DOI:10.1055/s-0030-1258032

Irradiations of alkyl phenylglyoxylates with sulfur-containing carboxylates yielded the corresponding photodecarboxylative addition products in moderate to good yields of 26-58%. Reductive photodimerization competed with decarboxylative addition in all ca

Full text of DOI:10.1055/s-0030-1258032

2240
LETTER
Photodecarboxylative Additions of a-Thioalkyl-Substituted Carboxylates to
Alkyl Phenylglyoxylates
Photoaddition
u
of Sulfur-Containin
B
g Carboxylates
e
e
yoxylates Tan,a Oksana Shvydkiv,a Jana Fiedler,a Fadi Hatoum,a Kieran Nolan,a Michael Oelgemöller*b
a
Dublin City University, School of Chemical Sciences and NCSR, Glasnevin, Dublin 14, Ireland
James Cook University, School of Pharmacy and Molecular Sciences, Townsville, Queensland 4811, Australia
Fax +61(7)47816078; E-mail: michael.oelgemoeller@jcu.edu.au
b
Received 25 May 2010
In all cases, the desired alkylation products 4a–e and 5a–
e were obtained as main products together with the corre-
sponding reductive dimerization product 6 and 7
(Table 1). Isolation by column chromatography furnished
Abstract: Irradiations of alkyl phenylglyoxylates with sulfur-con-
taining carboxylates yielded the corresponding photodecarboxyla-
tive addition products in moderate to good yields of 26–58%.
Reductive photodimerization competed with decarboxylative addi-
tion in all cases. The reaction protocol was successfully transferred products 4 and 5 in moderate to good yields of 26–58%.
to a microreactor. With potassium 2-(methylsulfanyl)propionate,
photoadditions gave diastereomeric mixtures with low selectivity
for the like-isomer.
Irradiation of 1 in the presence of 10 equivalents of 3a did
not prevent the formation of the undesired dimerization
product 6 and effectively the same ratio of 4a/6 (76:24)
Key words: photodecarboxylation, phenylglyoxolates, photo-
was obtained. Likewise, irradiations of the 1/3a pair at
chemistry, photoinduced electron transfer, microreactor
300 nm in either aqueous acetonitrile or aqueous acetone
gave no improvements in terms of yields or selectivities.
The simple reaction protocol was furthermore applied to
The photochemistry of phenylglyoxylates and phenylgly-
‘microphotochemistry’.9 A commercially available mi-
oxylamides has been intensively studied over the last de-
croreactor (dwell device, mikroglas), which was placed
cades.1–5 Among the many transformations examined are,
under a UV panel (Luzchem) fitted with 5 UVA lamps,
for example, Norrish,1 Paternò–Büchi,2 photoreduction,3
was chosen (Figure 1).10 The synthesis of 4a was again
and photocyclization reactions.4 For the related phthalim-
used as a model. Using a residence time of one hour, a 4a/
ide chromophore, we have recently developed the photo-
6 mixture of 76:24 was isolated.
decarboxylative addition of carboxylates as a versatile
alkylation method and alternative to Grignard additions.6
The procedure utilizes easily accessible carboxylic acid
salts and has been scaled up using a 308 nm excimer sys-
tem.7 We therefore became interested in applying the
photodecarboxylation protocol to simple alkyl phenylgly-
oxylates and a-thioalkyl-substituted carboxylates. Five
sulfur-containing carboxylates 3a–e were thus irradiated
at 350 nm in aqueous acetonitrile in the presence of either
methyl or ethyl phenylglyoxylate (1 and 2, Scheme 1).8
Figure 1 Microreactor (dwell device, mikroglas) under a UV expo-
sure panel (Luzchem)
O
R3
OR1
The diastereoselectivity of the reaction was furthermore
R2
+
studied for the branched potassium 2-(methylsulfa-
nyl)propionate 8 (Scheme 2, Table 2). In both cases, the
diastereomeric ratio was determined by integration of
S
CO2K
O
1, 2
3a–e
hν
MeCN–H2O
1
baseline-separated signals in the H NMR spectra of the
crude product as 1:1.1 in favor of the like-diastereomer.11
The photoaddition products were isolated in good yields
of 55% (9) and 51% (10).
R3
R2
S
HO
HO
)
2
OR1
OR1
+
In order to demonstrate the superiority of the photodecar-
boxylation protocol, 1 was irradiated in dry acetonitrile in
the presence of 5 equivalents of 1,3-dithiane (11). Com-
pound 11 is advantageous over other thioethers since it is
a solid and thus easier to work with. After exhaustive irra-
diation of 22 hours, a 20:80 mixture of 4e and 6 was ob-
tained. Purification by column chromatography furnished
the desired addition product 4e in a low yield of 16%.
O
O
4, 5a–e
6, 7
Scheme 1 Photoreaction of 1/2 with sulfur-containing carboxylates
3a–e
SYNLETT 2010, No. 15, pp 2240–2243
Advanced online publication: 12.08.2010
x
x
.x
x
.2
0
1
0
DOI: 10.1055/s-0030-1258032; Art ID: D12810ST
© Georg Thieme Verlag Stuttgart · New York

LETTER
Photoaddition of Sulfur-Containing Carboxylates to Phenylglyoxylates
2241
Table 1 Product Compositions and Experimental Details for Photoadditions of 1/2 with 3a–e
Glyoxylate
R1
Carboxylate
R2
R3
Time (h)
Product composition (%)a
Yield (%)b
4/5
77
88
90
81
66
85
65
77
67
65
6/7
23
12
10
19
34
15
35
23
33
35
4/5
37
50
53
58
27
44
44
43
36
26
1
1
1
1
1
2
2
2
2
2
Me
Me
Me
Me
Me
Et
3a
3b
3c
3d
3e
3a
3b
3c
3d
3e
Me
Et
H
H
H
H
1
2
2
3
4
2
2
2
2
4
Ph
Bn
(CH2)3S
Me
Et
H
H
H
H
Et
Et
Ph
Bn
Et
Et
(CH2)3S
a Determined by 1H NMR spectroscopy of the crude reaction mixture.
b Isolated yield.
O
The general mechanistic scenario for photodecarboxyla-
tive additions of a-thioalkyl-substituted carboxylates to
alkyl phenylglyoxylates is depicted in Scheme 3. Based
on the available electrochemical and spectroscopic data of
simple phenylglyoxylates, the limiting maximum oxida-
tion potential for an exergonic photoinduced electron
transfer has been established to 1.7 V (vs. SCE).4b,12 Due
OR1
+
MeS
CO2K
O
1, 2
8
hν
MeCN–H2O
to the low oxidation potential of thioethers (for Me2S:
–
E
Ox = 1.23 V vs. SCE13) vs. carboxylates (for MeCO2 :
SMe
OR1
SMe
OR1
HO
HO
calcd EOx = 1.54 V in MeCN vs. SCE14), electron transfer
to the triplet excited phenylglyoxylates is expected to oc-
cur predominately from the sulfur atom. Subsequent a-de-
carboxylation of the thioether radical cation gives the
corresponding carbon-centered radical. Carbon bond for-
mation and protonation furnishes the addition products 4,
5, 9, and 10, respectively (Scheme 4). Consequently, the
mechanism parallels that of the related phthalimide sys-
tem.15
+
+
6, 7
O
O
l-9, 10
u-9, 10
Scheme 2 Addition of potassium 2-(methylsulfanyl)propionate 8 to
1/2
Table 2 Product Compositions and Experimental Details for Photo-
additions of 1/2 with 8
Glyoxylate R1
Time (h) Product compositiona
Yield (%)b
Alternatively, the alkyl phenylglyoxylate radical anions
dimerize to the reduction products 6 and 7. Similar com-
petitive scenarios have been reported for other hydrogen
and electron donors.3 The differences in yields and selec-
tivities when changing from the methyl ester 1 to the ethyl
ester 2 suggest that intramolecular H abstraction may
compete with photodecarboxylation.1
9/10
80
6/7
20
40
l/u
9/10
1
2
Me
Et
4
4
1.1:1
1.1:1
55
51
60
a Determined by 1H NMR spectroscopy of the crude reaction mixture.
b Isolated yield.
In comparison with simple thioethers (as 11),16 the decar-
boxylation pathway (using 3e) is much more efficient and
chemoselective. Hence, the carboxylate group in a-posi-
tion to the thioether functions as a powerful activating
group for PET reactions. Furthermore, addition occurs ex-
clusively at the carbon that carries the directing carboxy-
late function. For thioethers themselves, competing
nonproductive electron and proton back-transfer reduces
the overall efficiency for addition.9,15a In addition, asym-
S
O
S
HO
OMe
OMe
hν
S
+
+ 6
MeCN
O
O
S
11
1
4e
Scheme 3 Photoreaction of 1 with 1,3-dithiane 11
Synlett 2010, No. 15, 2240–2243 © Thieme Stuttgart · New York

2242
S. B. Tan et al.
LETTER
J. Org. Chem. 1997, 62, 564. (f) Buhr, S.; Griesbeck, A. G.;
Lex, J. Tetrahedron Lett. 1996, 37, 1195.
(3) (a) Hu, S.; Neckers, D. C. J. Photochem. Photobiol. A:
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(c) Huyser, E. S.; Neckers, D. C. J. Org. Chem. 1964, 29,
276.
O–
R3
R3
3
PETs
R2
R2
*
+
1, 2
+
Ph
CO2R1
S
•
CO2
–
–
•
S
CO2
+
3, 8
– CO2
+ H+, x 2
O–
R3
R2
(4) (a) Hu, S.; Neckers, D. C. J. Org. Chem. 1997, 62, 7827.
(b) Hu, S.; Neckers, D. C. J. Org. Chem. 1997, 62, 6820.
(c) Hu, S.; Neckers, D. C. Tetrahedron 1997, 53, 7165.
(d) Hu, S.; Neckers, D. C. Tetrahedron 1997, 53, 2751.
(5) (a) Lavy, T.; Sheynin, Y.; Sparkes, H. A.; Howard, J. A. K.;
Kaftory, M. Cryst. Eng. Comm. 2008, 10, 734.
S
OR1
HO
CO2R1
•
Ph
•
R2
6, 7
S
R3
+ H+
O
4, 5, 9, 10
Scheme 4 Mechanistic scenario
(b) Griesbeck, A. G.; Heckroth, H. Synlett 2002, 131.
(c) Zehavi, U. J. Org. Chem. 1977, 42, 2821.
(6) (a) Gallagher, S.; Hatoum, F.; Zientek, N.; Oelgemöller, M.
Tetrahedron Lett. 2010, 51, 3639. (b) Hatoum, F.;
Gallagher, S.; Oelgemöller, M. Tetrahedron Lett. 2009, 50,
6593. (c) Hatoum, F.; Gallagher, S.; Baragwanath, L.; Lex,
J.; Oelgemöller, M. Tetrahedron Lett. 2009, 50, 6335.
(d) Kim, A. R.; Lee, K.-S.; Lee, C.-W.; Yoo, D. J.; Hatoum,
F.; Oelgemöller, M. Tetrahedron Lett. 2005, 46, 3395.
(e) Oelgemöller, M.; Cygon, P.; Lex, J.; Griesbeck, A. G.
Heterocycles 2003, 59, 669. (f) Griesbeck, A. G.;
Oelgemöller, M.; Lex, J. Synlett 2000, 1455. (g) Griesbeck,
A. G.; Oelgemöller, M. Synlett 2000, 71. (h) Griesbeck,
A. G.; Gudipati, M. S.; Hirt, J.; Lex, J.; Oelgemöller, M.;
Schmickler, H.; Schouren, F. J. Org. Chem. 2000, 65, 7151.
(i) Griesbeck, A. G.; Oelgemöller, M. Synlett 1999, 492.
(j) Belluau, V.; Noeureuil, P.; Ratzke, E.; Skvortsov, A.;
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Lett. 2010, 51, 4738.
metrically substituted thioethers commonly give mixtures
of regioisomers.17
In conclusion, a-thioalkyl-substituted carboxylates under-
go photodecarboxylative addition to alkyl phenylglyoxy-
lates. Conversion rates, isolated yields and selectivities
were higher compared to reactions with simple thioethers.
The easy procedure was suitable for adaptation in ‘micro-
photochemistry’.
Acknowledgment
This research project was financially supported by Science Found-
ation Ireland (SFI, 07/RFP/CHEF817 and 06/RFP/CHO028), the
Environmental Protection Agency (EPA, 2008-ET-MS-2-S2) and
the Department of Environment, Heritage and Local Government
(DEHLG, 2008-S-ET-2). The authors would like to thank Dr. An-
dreas Freitag (mikroglas chemtech) for technical advice and sup-
port.
(7) (a) Griesbeck, A. G.; Maptue, N.; Bondock, S.; Oelgemöller,
M. Photochem. Photobiol. Sci. 2003, 2, 450. (b) Griesbeck,
A. G.; Kramer, W.; Oelgemöller, M. Green Chem. 1999, 1,
205.
(8) General Procedure for Irradiation
The alkyl phenylglyoxylate (1.5 mmol) was dissolved in
MeCN (50 mL). A solution of the potassium carboxylate
(4.5 mmol) in H2O (50 mL) was added, and the mixture was
irradiated (Rayonet Photochemical Reactor RPR-200;
l = 350 30 nm) at 15–20 °C in a Pyrex tube (l ≥ 300 nm)
while purging with a slow stream of nitrogen. The progress
of the reaction was monitored by TLC analysis or by passing
the departing gas stream through a sat. Ba(OH)2 solution
until precipitation of BaCO3 had ceased. Most of the MeCN
was evaporated, and the remaining solution was extracted
with EtOAc (4 × 25 mL). The combined organic layers were
washed with 5% NaHCO3 (1 × 25 mL) and brine (1 × 25
mL), dried over MgSO4, and evaporated. The products
were purified by flash column chromatography (eluent:
n-hexane–EtOAc = 5:1).
References and Notes
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Selected Physical and Spectral Data for the Product
Methyl-2-(1,3-dithian-2-yl)-2-hydroxy-2-phenylacetate
(4e)
Yellowish solid, mp 104–106 °C. Rf = 0.39 (SiO2, n-hexane–
EtOAc = 5:1). 1H NMR (400 MHz, acetone-d6): d = 1.84 (m,
2 H, CH2), 2.40–2.46 (m, 1 H, SCH2), 2.56–2.62 (m, 1 H,
SCH2), 3.02–3.09 (m, 1 H, SCH2), 3.19–3.26 (m, 1 H,
SCH2), 3.61 (s, 3 H, OCH3), 4.48 (s, 1 H, CH), 5.14 (s, 1 H,
OH), 7.14–7.24 (br m, 3 H, Harom), 7.56 (dd, 3J = 8.4 Hz,
4J = 1.6 Hz, 2 H, Harom) ppm. 13C NMR (100 MHz, CDCl3):
d = 25.1 (t, 1 C, CH2), 28.0 (t, 1 C, SCH2), 28.3 (t, 1 C,
SCH2), 50.4 (d, 1 C, CH), 53.9 (q, 1 C, OCH3), 85.1 (s, 1 C,
COH), 126.0 (d, 2 C, CHarom), 128.3 (d, 1 C, CHarom), 128.4
(d, 2 C, CHarom), 139.1 (s, 1 C, Cqarom), 173.8 (s, 1 C, C=O)
ppm. IR (KBr): n = 3490, 2953, 2925, 2892, 1725, 1239,
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Synlett 2010, No. 15, 2240–2243 © Thieme Stuttgart · New York

LETTER
Photoaddition of Sulfur-Containing Carboxylates to Phenylglyoxylates
2243
733, 692 cm–1. MS (EI, 70 eV): m/z (%) = 284 (<1) [M+],
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and has a total path length of 1.15 m (20 turns) on a 118 mm
× 73 mm aperture. The reactor consisted of a(bottom)
serpentine reaction channel 0.5 × 2 mm (D × W), with a
second(top), heat-exchanging channel through which water
is passed in order to control the reactor temperature. The
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reaction channel via a syringe pump and collected in a test
tube.
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(16) Irradiation of 2 in benzene and in the presence of 5 equiv of
Me2S gave the corresponding addition product 5a in a yield
of 35%. Selectivity (7 vs. 5a) was determined as 60:40.
Similar results were obtained with 1,3-dithiolane.3a
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