Electron-catalyzed radical perfluoroalkylation of organic sulfides: The serendipitous use of the TMEDA/I2 complex as a radical initiator

Article abstract of DOI:10.1039/c7cy00236j

Radical initiation for the perfluoroalkylation reaction of sulfides has been performed using the complex [(TMEDA)I·I₃] and visible light. This methodology bypasses the use of metal(organo)catalysts where the complex [(TMEDA)I·I₃] acts as a good electron donor/reductant radical initiating agent. Biologically relevant sulfides are easily substituted with R_F moieties employing a mild and environmentally benign radical strategy starting from readily available R_FI.

Full text of DOI:10.1039/c7cy00236j

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ARTICLE
ELECTRON-CATALYZED RADICAL PERFLUOROALKYLATION OF
ORGANIC SULFIDES. THE SERENDIPITOUS USE OF TMEDA/I2
COMPLEX AS RADICAL INITIATOR
Received 00th January 20xx,
Accepted 00th January 20xx
D.E. Yerien,a S. Barata-Vallejo*,a, B. Camps,a A.E. Cristófalo,b M.E. Cano,b M.L. Uhrig,b A. Postigo*,a
DOI: 10.1039/x0xx00000x
Radical initiation for the perfluoroalkylation reaction of sulfides has been performed using the complex [(TMEDA) I.I3] and
visible light. This methodology bypasses the use of metal(organo)catalysts where the complex [(TMEDA) I.I3] acts as a good
electron donor / reductant radical initiating agent. Biologically-relevant sulfides are easily substituted with RF moieties
www.rsc.org/
employing
a
mild and environmentally benign radical strategy starting from readily-available RFI.
Electrophilic perfluoroalkyl radicals RF derived from RF-I
have recently been informed to functionalize sulfide RSH
residues very efficiently[6], when the reactions are initiated by
Introduction
Perfluoroalkyl sulfides have found wide applications, such as in
liquid crystal displays[1],[2], for oleophobic surface coatings[3], as
well as in the synthesis and development of potential
hypotensive agents for clinical use containing SRF moieties
such as Losartan derivatives (Dup 753) in Figure 1.[4]
visible light and a metal-photocatalyst in the presence of
N,N,N´,N´-tetramethylethylene diamine, TMEDA, in MeCN as
solvent. In the past, the perfluoroalkylation of sulfides has
been accomplished by different methods under diverse
reaction conditions,[4],[7],[8],[9],[10],[11],[12] such as those indicated
in Scheme 1.
hυ
Boiko & Yagupolskii (1977)
Ikeya (1988)
SRF
liquid NH3
SH
R
MV2+, NEt3
DMF
FI
R
NEt3
R
Boiko & Shchupak (1994)
MeCN
hυ
Soloshonok (1992)
liquid NH3
Togni`s reagent
MeCN/H2O
R
FI
Togni & Seebach (2008)
R
RS-
RSH
F
Figure 1. Losartan analogs containing S-RF
Photeredox catalyst, hυ
Noel (2016)
In order to avoid the use of gaseous CF3I for the
MeCN
flow system
trifluoromethylation
of
sulfides
RS-H,
several
(TMEDA)I.I3, hυ
trifluoromethylthiolating reagents have appeared in the
literature in order to effect late-stage SCF3 substitutions;
however, fewer direct perfluoroalkylthiolating reagents are
known to date.[5] To that effect, the direct perfluoroalkylation
of sulfides still remains a simple and viable strategy towards
the synthesis of perfluoroalkylsulfides.
R
R(Ar)-S
F
R
FI
R(Ar)-SH
+
MeCN
this paper
Scheme 1. Methods for radical perfluoroalkylation of thiols by
RFI
Inspired by the results of Noel and collaborators[6] for the
perfluoroalkylation of cysteine derivatives employing TMEDA,
RF-I and a transition metal photoorganocatalyst, we replaced
our reported strategy for the radical perfluoroalkylation
[13]
reactions using Cs2CO3 for TMEDA and used a commercial
fluorescent light CFL in the absence of an organophotocatalyst
(POC). In this work, we will show the serendipitous discovery
of a radical initiation event from visible light irradiation of a
complex between TMEDA and I2 (i.e. :[(TMEDA) I.I3]) which
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triggers an electron-catalyzed process towards the synthesis of
perfluoroalkyl sulfides in improved substitution yields.
Results and discussion
Table 1. Optimization of reaction conditions for the perfluoroalkylation of organic thiols R-SX (0.2 mmol), with a perfluoroalkyl
iodide RFI (1.5 equiv.), an additive (1.5 equiv.), under diverse reaction conditions (2 h reaction, 25
°C, Ar-deoxygenated)
Entry
R
X
Additive
RFI
Conditions
% RS-C4F9
h
νa,b
1
Ph
H
Cs2CO3
n-C4F9I
80
c
2
3
Ph
Ph
H
H
Cs2CO3
TMEDA
TMEDA
TMEDA
-
n-C4F9I
n-C4F9I
n-C4F9I d
n-C4F9I
n-C4F9I
n-C4F9I d
n-C4F9I
n-C4F9I d
n-C4F9I
n-C4F9I
n-C4F9I
63
80
11
30
-
h
νa
4
Ph
H
h
νa
c
5
Ph
H
6
Ph
H
h
νa
c
7
Ph
H
TMEDA
nBu4NIe
TMEDA
< 5
75
42
< 5
< 5
< 5
8
HOCH2CH2-
HOCH2CH2-
HOCH2CH2-
HOCH2CH2-
HOCH2CH2-
H
h
νa
9
H
TMEDA
TMEDA
TMEDA
-
h
νa
c
10
11
12
H
Na
Na
h
νa
νa
h
a
from the neat reagent n-C4F9I by passing through a neutral alumina column;
.- irradiation with a commercial fluorescent lamp CFL, 60 Watt;
b
.-Rose Bengal as photocatalyst, 0.1 equiv.;
[
c.-dark reaction conditions; d.-dissolved iodine was excluded
e
.- n-Bu4NI] = 0.2 equiv
under visible-light (CFL) in MeCN as solvent. Under these latter
The visible light-Rose Bengal (RB)-photocatalyzed reaction of conditions, we obtained only 11 % yield of product (entry 4,
benzene thiol in the presence of Cs2CO3 and n-C4F9I affords 80 Table 1), indicating that the residual absorption of benzene
% yield of PhS-C4F9 (entry 1, Table 1). Under dark reaction thiolate at the irradiation wavelengths with a CFL is not
conditions, a 63 % yield of product (entry 2, Table 1) is sufficient for maintaining the radical chain and that the
1
1
1
obtained.[14] These results are very encouraging in terms of presence of I2 is intervening in the initiation process.
initiation efficiency and chain propagation by the Cs2CO3 At this point, the evidence showed that in the absence of POC
salt.[14] Replacing Cs2CO3 for the less expensive TMEDA affords [13] (RB) and presence of TMEDA, product formation seemed to
80% yield of product
1
under visible light irradiation (entry 3, improve substantially upon illumination (entries 3, 8, Table 1)
when traces of I2 were present in commercial n-C4F9I.
Table 1) in the absence of POC.
We suspected that, in the absence of POC (i.e. Rose Bengal) The photoreaction of benzenethiol in the absence of TMEDA
and presence of TMEDA, the residual absorption of benzene (entry 6, Table 1), does not afford any product. The dark
thiolate[15],[4] at the irradiation wavelengths of the commercial reaction in the presence of n-Bu4NI, a known thermal radical
fluorescent lamp CFL, could start the reaction through the initiator,[19] affords < 5% yield of product
well-known photoinduced electron transfer initiation process The photoreaction of
-mercaptoethanol[9] in the presence of
from thiolates to RFI.[16],[4] n-C4F9I and TMEDA, affords 75% yield of HOCH2CH2S-C4F9 2[9]
The UV-vis spectrum of a solution mixture of commercial n- (entry 8, Table 1). Excluding the presence of dissolved iodine,
C4F9I to be irradiated at the working concentrations shows an reduces the yield of to 42% (entry 9, Table 1). Under dark
absorption band with λmax = 458 nm, corresponding to the conditions, a low yield of product is obtained (< 5%, entry 10,
absorption of iodine in MeCN (Figure S1, Supporting Table 1). The photoreactions of the sodium salt of
1 (entry 7, Table 1).
β
2
2
β
-
Information), with enough optical density to initiate the radical mercaptoethanol, either in the presence or absence of
reaction through the production of iodine atoms.[17],[18] TMEDA, do not afford appreciable quantities of product
Concerned about this absorption, we excluded dissolved (entries 11, 12, Table 1), emphasizing the role of the organic
iodine from the neat reagent n-C4F9I, passing the neat liquid covalent salt RS-TMEDAH+.
through a neutral alumina column, and subjected the mixture A complex between TMEDA and I2 (i.e.:
of RSH, iodine-free n-C4F9I, and TMEDA to the photoreaction reported by Adam and colleagues[20], with λmax = 360 nm in
[(TMEDA) I.I3] has been
2 | J. Name., 2012, 00, 1-3
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MeCN, (
4.7 x 107 M-1 and ECT = 4.35 eV). Due to the traces of I2 present mixtures of TMEDA and I2, confirming the remarkable increase
in the neat starting n-C4F9I, we consider convenient to inspect in the absorptivity at 360 nm (
= 4x104 M-1cm-1 in MeCN),
ε
= 4x104 M-1cm-1, a complex formation constant ca. initiation process. Figures S2-S3, show the UV-vis spectra of
ε
whether complexation of these trace amounts of I2 present in responsible for the absorption of light.
n-C4F9I with TMEDA could be responsible for the radical
Table 2: % Yields of perfluoroalkylation of organic sulfides RS-H (0.2 mmol) with RFI (1.5 equiv.) in the presence of TMEDA (1.5
equiv.) in MeCN as solvent and visible light in de-oxygenated (Ar) atmosphere
.
___________________________________________________________________________
C4F9
S
O
OCH3
O
OAc
O
O
AcO
AcO
SC4F9
H3CO
HO
AcO
AcO
C
S
4F9
C4F9
S
HN
O
OAc
OAc
8, 83 %c , 64%c,d,e
O
4, 50%a, 25 %b
6, 75 %c,d,e
2, 75 %
C F
NH2
S
4
9
OAc
O
OAc
O
C F
S
AcO
AcO
4
9
C F
S
4
9
C F
S
4
O
9
AcO
H3C
SC4F9
13, 50%
OAc
OAc
10, 50 %c,d,e
11, 90 %a,f
1, 80 %
NH2
N
N
N
SC4F9
N
N
N
SC4F9
H
b,g
15,
48 %
17, 50 %
H
N
S
S
C F
S
4
9
C F
S
C F
S
8
17
4
9
N
N
N
C4F9
19, 99 %
20, 80 %
22, 50%
a.-%NMR yield; b.- isolated yield; c.-24-h reaction; d.- in the presence of RB and Cs2CO3; e.-with excess of n-C4F9I; f.- 20 h reaction; g.- in DMSO:
DMF 1 :2-
UV-vis spectra of mixtures of iodine-free n-C4F9I and TMEDA S1, there seems to be the presence of complexes between
do not show a distinct change in absorption or extinction perfluoroalkyl iodides and thiols[23], the existence of which
coefficients. The TMEDA•2-CF3I complex has been reported result in chemical shift changes of the signal from I-CF2-RF in
before[21]
,
based on calculations, X-Ray crystallographic the 19F NMR spectra when n-C4F9I is in the presence of the RSH
13
analysis, and spectroscopic data (1H, 19F, C NMR). The same as compared with the innate chemical shift value of ICF2-RF
trends for the formation of a complex TMEDA•2C4F9I[22] based signal, interpreted as halogen bonding to the sulfur atom of
on NMR data (19F NMR) is presented in Table S1, showing the substrate.[24] We have observed the same trends in the 19
F
/
spectral changes going from free reagents to the complexed NMR spectra of mixtures of TMEDA
amino(hetero)aromatic compounds.[22]
/
RFI
mixtures.
The 19F NMR upfield shifts observed in the I-CF2-C3F7 are In a previous report[22] we have shown the efficient visible
indicative of a debilitated I-C bond in n-C4F9I when TMEDA is light-initiated reaction of 2-mercaptoaniline with n-C4F9I at the
present, being the largest shift when a stoichiometry of the sulfur atom (product 11, Table 2) in the absence of
complex TMEDA: 2C4F9I is reached (Table S1). Also, from Table organophotocatalyst and presence of TMEDA. Encouraged by
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this result, and that from Noel and collaborators on the 2-Mercaptobenzothiazol[29] 18 gives product 19 in 99% yield.
perfluorobutylation of cysteine derivatives in the presence of When n-C8F17I is used instead of n-C4F9I, product 20 is isolated
TMEDA and a transition-metal photoorganocatalysts,[6] we in 80% yield.
attempted the perfluoroalkylation of organic sulfides, as 1H-Benzo[d]imidazole-2-thiol 21, affords 50% yield of di-
shown in Table 2, in the presence of
CFL and absence of photoorganocatalyst. The concentration of ((perfluorobutyl)thio)-1H-benzo[d]imidazole
the complex between I2-contaminated n-C4F9I and TMEDA was For the reaction of sulfides, an ET mechanism between visible
ca. 0.25 mM. light-excited sulfides and RFI has been accepted as initiation
The reaction of 2-mercaptoethanol under conditions of Table process, where the radical anion of the substitution product is
2, affords 75% yield of product
. Noncanonical aminoacids the chain carrier.[4] The reaction, depending on the substrate,
[(TMEDA)I.I3] complex, a substituted compound 22 (Table 2), i.e.: 4-(perfluorobutyl)-2-
.
2
have proven to be efficient tools to advantageously modulate has a thermal spontaneous component (see entries 5, 9, Table
the biophysical and biochemical properties of peptides and 1) that contributes to some product formation.
proteins. Moreover, owing to its nearly total absence in Notwithstanding, the reaction is always accelerated after
biological media, fluorine is an outstanding bioorthogonal irradiation under the conditions illustrated in Table 2. When
atom useful as a probe for NMR spectroscopy to explore the reactions of sulfides were carried out in the absence of
conformational changes in peptides and proteins and their
interactions with other biological molecules.[25] We therefore under visible light irradiation, low yields of substitution
embarked on exploring the perfluoroalkylation of cysteine products were obtained (entries 4, 6, Table 1). The dark
[(TMEDA) I.I3] complex (i.e.: I2 excluded or absence of TMEDA),
derivative
3
, which affords product
4
in 50 % yield (Table 2, reactions in the presence of the complex [(TMEDA) I.I3] afford
lower yields of substitution products (entries 5, 10, Table 1).
purified yield 25%).
Pefluoroalkylated thiosugar derivatives have been paid much Taking into account the presence of dissolved iodine in
attention in the last decades due to their useful liquid– commercial RFI, the use of TMEDA can aid in the initiation
crystalline properties[1] and relevance as surfactants and process through the
[(TMEDA) I.I3] complex formation. This is
emulsifiers for “water-in-fluorocarbon” emulsions.[26a] On the likely the case in many studies[6],[30],[31a] where a combination
other hand, the sulfur atoms in thiosugars make the of RFI, TMEDA, and visible light is employed. In fact, a very
interglycosidic bonding stable to glycosidases.[26b-d] The recent report on the trifluoromethylation of alkynes in the
incorporation of a hydrophobic chain as aglycone, such as a presence of TMEDA and that of heteroaromatics and alkenes
perfluorinated residue, could have a high impact in protein– in the presence of DBU with CF3I shows that the reactions
carbohydrate recognition events which take place between proceed in good-to-excellent yields when irradiated with white
sugars and glycosidases, glycosyltransferases and also lectins. light and absence of photocatalyst. However, no explanation is
For these reasons, fluorinated thiosugars have
a
great supplied.[31b]
potential as tools in the field of Glycobiology. To that effect, The reactions in the presence of TEMPO ((2,2,6,6-Tetramethyl-
we proceeded to studying the S-perfluoroalkylation of piperidin-1-yl)oxyl, a well-known radical scavenger) as well as
thiocarbohydrates. The reactions of the sugar thioaldoses[26] in the presence of 1,4-dinitrobenzene afford little or no
2,3,4-tri-O-acetyl-1-thio-β
and 2,3,4,6-tetra-O-acetyl-1-thio-
-D-glucuronic acid methyl ester[27]
-D-galactopyranose[26]
5
7
substitution products, indicating the presence of radicals.
β
For the visible light irradiation of amino-(hetero)aromatic
under our standard reaction conditions, afford 75 and 83 % compounds in the presence of RFI and TMEDA we have
yields of SC4F9 -substituted products and
respectively previously proposed[22] a reaction mechanism, where the
(Table 2). The disaccharide 2´,3´,4´,6´,2,3,6-hepta-O-acetyl-1- visible light-excited complex (TMEDA) I.I3 produces iodine
thio- -D-cellobiose capable of abstracting I from n-C4F9I producing
affords product 10 in 50 % yield as atoms[32],[33] [34]
indicated in Table 2. However, the reaction of galactoside- n-C4F9 radicals that commence the radical reaction. However,
disulfide (1,1´-bis-(2,3,4,6-tetra-O-acetyl-1-thio- -D- the visible light irradiation of the complex (TMEDA) I.I3 in the
galactopyranose)) did not afford any S-C4F9 substitution presence of oleic acid methyl ester (see Supporting
6
8
[
]
β
9
,
β
[
]
product.
Information) does not produce the corresponding trans-fatty
Benzene thiol affords
1
in 75-80% yield, whereas 2- acid methyl ester, indicating that iodine atoms, if produced, do
mercaptoaniline gives product 11 in 90% yield. When the not
dithiol 4-methylbenzene-1,2-dithiol 12 is treated under efficiency.[17],[18],[35],[33],[32],[34],[36] We have[22] also found that
reaction conditions from Table 2, 50 % yield of 13 is obtained. TMEDA is not acting as sacrificial donor in the
induce
the
isomerization
process
with
a
When 2-mercapto-4-amino-pyrimidine 14 is subjected to the perfluoroalkylation of amino(hetero)aromatic compounds
same reaction conditions, a 48% yield of product 15 is under visible light-irradiation, as very little decomposition of
observed.
When
TMEDA into a carbonyl compound was detected, as in eq. 1
(see Supporting Information). Therefore, the complex
5H-[1,2,4]triazino[5,6-b]indole-3-thiol
16,
a
dihydrofolate reductase (DHFR) inhibitor,[28] which has
[(TMEDA) I.I3] does not undergo significant ET to n-C4F9I to
successfully been used as a drug target in the area of parasitic produce the radical cation of TMEDA according to eq. 1. [37]
diseases is subjected to reaction conditions of Table 2, a 50%
yield of product 27 is found.
4 | J. Name., 2012, 00, 1-3
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-H+
ET
RFI RF
ET
carbonyl
compound
N
N
N
N
TMEDA
N
N
N
N
RFI RF
(1)
Another possibility should be considered: that of the complex Reaction solvents such as acetonitrile, were chromatography
(TMEDA) I.I3 acting as a radical initiator. Organic iodides such quality and were not further purified. Chromatography and
[
]
as n-Bu4NI, and inorganic iodide salts XIn (where X = Na, K, Li, extraction solvents dichloromethane, chloroform, iso-octane,
Cu (with n=1), Fe (n = 2), Ni (n = 2)) are known to act as radical n-hexane, n-heptane, ethyl acetate, acetone, and, ethanol
initiators under thermal conditions.[38] In the proposed were purchased from commercial suppliers.
mechanism (Scheme 2), electrons from excited (under N,N,N´,N´-tetramethylethylene diamine TMEDA was 99% pure
illumination conditions) or ground state (under dark thermal and used as received from the supplier. Fluorinated reagents
conditions) complex
[
(TMEDA) I.I3
]
radical of RF• and iodide anion. This process is facilitated in iodide),
reduce RFI, forming the 1,1,1,2,2,3,3,4,4-nonafluoro-4-iodobutane
(perfluorobutyl
1,1,1,2,2,3,3,4,4,5,5,6,6,7,7,8,8-heptadecafluoro-8-
view of the debilitated RF-I bond in the TMEDA•2C4F9I iodooctane were used as received from the supplier without
complex (Table S1); reaction with RS- (or the TMEDA salt) further purification, except when traces of iodine had to be
would ensue, leading to the formation of the radical anion of removed, in which case, the neat liquid was passed through a
the substitution product RSC4F9
(or the complex TMEDA•2C4F9I) yields thermoneutral RSC4F9 and purified by column chromatography or vacuum-distilled;
and further electrons to maintain the chain. This possibility the synthesis of sugar thioaldoses 2,3,4-tri-O-acetyl-1-thio-
does not entail the formation of the radical cation of TMEDA. D-glucuronic acid methyl ester and 2,3,4,6-tetra-O-acetyl-1-
In this respect, TMEDA is acting as a complexing agent to thio- -D-galactopyranose and disaccharide 2´,3´,4´,6´,2,3,6-
hepta-O-acetyl-1-thio- -D-cellobiose have been
accomplished by standard techniques and are given in section
2,2,6,6-Tetramethyl-1-piperidinyloxy (TEMPO) and 1,4-
•-, which by further ET to RFI neutral alumina column. Sulfides were commercially available
β
-
5
β
7
iodine, and a Brønsted base to deprotonate RS-H.
β
9
hυ
D
.
(TMEDA) I.I3
*
(TMEDA) I.I3
dinitrobenzene were Ultra-pure grade. Dye Rose Bengal
(4,5,6,7-Tetrachloro-3',6'-dihydroxy-2',4',5',7'-tetraiodo-3H-
spiro[isobenzofuran-1,9'-xanthen]-3-one), was 99.9% pure and
used as received from the supplier. Yields were referred to as
isolated yields of analytically pure material unless otherwise
n-C4F9I
e-
RS-C4F9
TMEDAH
+
I-
1
noted, as the case of yields calculated from 19F NMR and H
NMR spectral integration.
electron-
catalyzed
n-C4F9
Reactions were magnetically stirred and monitored by thin-
layer chromatography (TLC) using Silica gel 60 F254 pre-coated
plates (0.25 mm, Merk), and revealed by UV-light or CAN
solution. Purification of the reaction products was carried out
by flash column chromatography using Ultra Pure Silica Gel
(230–400 mesh) or standard silica-gel for column
chromatography (60 mesh).
R-S- TMEDAH+
R-S-C4F9
TMEDAH
A
Scheme 2. Alternative proposed mechanism where the excited
complex (TMEDA) I.I3 undergoes outer-sphere ET with n-C4F9I
The light source was a commercially available household 60-
watt fluorescent light bulb or a 50 Watt black light (λmax = 370
nm).
[
]
1H NMR spectra were recorded on a Bruker Avance 600 (600
MHz) spectrometers, and are reported in ppm using the
solvent residual peak resonance as the internal standard
(dimethylsulfoxide-d6 at 2.54 ppm, CDCl3 at 7.26 ppm). 1H
NMR data are reported as follows: chemical shift; multiplicity;
number of hydrogens, coupling constants (Hz); H assignment
when necessary.
Experimental
A. GENERAL CONSIDERATIONS
All reactions were carried out in an argon atmosphere under
anhydrous conditions or otherwise noted.
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Multiplicity is abbreviated as follows: s = singlet, d = doublet, t methyl ester), and analyzed through capillary GC/MS with an
= triplet, dd = double doublet, m = multiplet, br = broad. appropriate capillary column (DB-5, 30 m). There was no
Proton-decoupled 13C NMR spectra were recorded on a Bruker conversion of oleic acid methyl ester into elaidic acid methyl
Avance 500 (at 125.758 MHz), or on a Bruker Avance 600 (at ester. This experiment rules out the production of I atoms
150.903 MHz) spectrometers and are reported in ppm using through irradiation of the complex
the C resonance signal from the solvent as the internal produced in sufficiently low quantities to enable the cis/trans
standard (acetone-d6 at 29.8 ppm, CDCl3 at 77.00 ppm). 19F isomerization. Conducting the irradiation with
black
[(TMEDA) I.I3], or else are
a
NMR spectra were recorded on a Bruker Avance 500 (at fluorescent light bulb (20 Watt), λmax = 370 nm from a black
470.592 MHz), or a Bruker Avance 600 (at 564.686 MHz) fluorescent light bulb), the same results were obtained.
spectrometers and are reported in ppm using the internal Experiment 2:
standard signal from the spectrometer. High-resolution mass Methyl oleate (0.5 mmol) was added to degassed MeCN (3 mL)
spectra (HRMS) were obtained using JEOL-DX 700 mass along with TMEDA (1 equiv) and I2-unfiltered C4F9I (3 equiv) in
spectrometer.
a 3 mL glass vial equipped with a screw-cap provided with a
septum containing a stirring bar. The set-up was placed on a
stir plate, sealed, and vigorously stirred throughout the
irradiation with a 60 Watt CFL bulb. Aliquots were taken at 30
min. intervals, added a standard, and analyzed through
capillary GC/MS with a DB-5 capillary column and an internal
standard (palmitic acid methyl ester). There was no conversion
of oleic acid methyl ester into elaidic acid methyl ester noticed
through irradiation time. This experiment rules out that I2
present in neat C4F9I, or else I2 produced through photolytic
cleavage of C4F9I complexes efficiently with TMEDA but do not
produce I atoms on irradiation capable of the cis/trans
isomerization of oleic acid methyl ester.
B. EXPERIMENTAL PROCEDURES AND CHARACTERIZATION DATA
B.1.-PREPARATION OF PRECURSORS AND SUSBTRATES
Sugar thioaldoses 2,3,4-tri-O-acetyl-1-thio-
methyl ester and 2,3,4,6-tetra-O-acetyl-1-thio-
galactopyranose were prepared by standard techniques. The
disaccharide 2´,3´,4´,6´,2,3,6-hepta-O-acetyl-1-thio- -D-
β
-D-glucuronic acid
5
β
-D-
β
cellobiose was also prepared by conventional techniques (see
characterization, for preparation procedures).
B2.-GENERAL PROCEDURE FOR THE (TMEDA.I).I3)-INITIATED
REACTIONS
In a 4 mL screw-cap vial provided with a micro stir bar,
(TMEDA) I.I3 complex, ca. 0.25 mM, substrate (0.2 mmol
thiol), photocatalyst Rose Bengal where needed (0.05 equiv)
and 3 mL of acetonitrile were introduced. The mixture was de-
oxygenated with a stream of Ar for 15 min. C4F9I or other RFI (3
equiv) was introduced by microliter syringe, and the vial
sealed. The closed reaction vessel was placed in front of a 60
Watt household fluorescent light bulb (or 20 Watt fluorescent
black light, λmax = 370 nm) and illuminated, under constant
vigorous stirring, for 24 hrs or otherwise noted. After the
reaction time was completed, the mixture was extracted thrice
with CH2Cl2 / water / brine. The organic layers were gathered
and dried over anhydrous Na2SO4, filtered and evaporated
under vacuo. The crude reaction mixture was purified by silica-
gel (60 mesh) column chromatography, with the eluants
indicated in the TLC conditions (vide infra, spectral data). The
polarity of the dye did not introduce any particular difficulty in
the separation and purification protocol, as the several CH2Cl2
extractions eliminated the PC. The eluants employed are
referred to in the TLC conditions of each compound.
D. CHARACTERIZATION OF COMPOUNDS
All compounds are unknown chemicals, unless otherwise
noted, and are reported as % yields obtained by weight or
NMR integration (from 1H and 19F NMR integration) of the
crude reaction mixtures. Isolated purified masses of
compounds are expressed in Gram units. Characterizations
employ 1H, 13C, 19F 1D-NMR techniques, and 2D NMR
spectroscopic techniques (HSQC, HMBC, COSY experiments)
2,3,4,6-tetra-O-acetyl-1-thio-β-D-galactopyranose 7
2,3,4,6-tetra-O-acetyl-1-thio-β-D-galactopyranose
was
obtained as previously described[39] and showed the same
properties as reported. Briefly, the thioaldose was obtained by
hydrolysis of the corresponding isothiouronium salt promoted
by sodium carbonate. The isothiouronium salt was in turn
obtained by reaction of acetobromogalactose with thiourea in
boiling acetone.
C.-TRIAL EXPERIMENT FOR THE CIS/TRANS ISOMERIZATION OF
OLEIC ACID METHYL ESTER
1H NMR (200 MHz, Cl3CD) δ = 5.45 (dd, 1H, J3,4 = 3.4, H-4), 5.20
(t, 1H, J2,3 = J1,2 = 10.0 Hz, H-2), 5.00 (dd, J3,4 = 3.4, J2,3 = 10.0Hz,
H-3), 4.55 (t, 1H, J1,2 = J1,SH = 10.0 Hz, H-1), 4.20 (m, 2H, H-6a,
H-6b), 3.95 (t, 1H, J5,6a = J5,6b, H-5), 2,40 (bs, 1H, SH), 2.09, 2.02,
1.97, 1.91 (4s, 12H, 4 CH3CO). 13C NMR (50.3 MHz, Cl3CD) δ =
170.3, 170.1, 169.9, 169.7 (4 COCH3), 79.2 (C-1), 74.9, 71.6,
70.8, 67.2 (C-5, C-3, C-2, C-4), 61.5 (C-6), 20.8, 20.7 (2×), 20.6
(4 COCH3).
Experiment 1:
Methyl oleate (0.5 mmol) was added to degassed MeCN (3 mL)
along with TMEDA (1 equiv) and I2 (2 equiv) in a 3 mL glass vial
capped with a screw-cap provided with septum and a stirring
bar. The set-up was placed on a stir plate, and vigorously
stirred throughout the irradiation with a 60 Watt CFL bulb
(commercial fluorescent light bulb). Aliquots were taken at 30
min. intervals, added an internal standard (palmitic acid
6 | J. Name., 2012, 00, 1-3
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ARTICLE
9.3, J4,5 = 9.9 Hz, H-4), 3.66-3.60 (m, 2H, H-5, H-5’), 2.13, 2.08,
2. 06, 2.02, 2.01, 2.00, 1.97 (7s, 21H, 7 CH3CO). 13C NMR (125
MHz, Cl3CD) δ = 170.6, 170.4, 170.3, 170.0, 169.8, 169.4, 169.2
(7 COCH3), 100.9 (C-1’), 78.6 (C-1), 77.3 (C-5), 76.4 (C-4), 73.9
(C-2), 73.3 (C-3), 73.0 (C-3’), 72.1 (C-5’), 71.7 (C-2’), 67.9 (C-4’),
62.2 (C-6), 61.7 (C-6’), 21.0, 20.9, 20.8, 20.7 (4×) (7 COCH3).
Bis(2,3,4,6-tetra-O-acetyl-1-deoxy-1-thio-β-D-
galactopyranosyl) 1,1’-disulfide 7S
5H-[1,2,4]triazino[5,6-b]indole-3-thiol 16 was prepared
42
]
according to literature procedures[ and the spectroscopic
data match well with the reported values.
The disulfide was obtained by oxidation of the corresponding
1-thio-β-D-galactopyranose.[40]
1H NMR (200 MHz, Cl3CD) δ = 5.43 (d, 1H, J3,4 = 2.8 Hz, H-4),
5.35 (t, 1H, J2,3 = J1,2 = 9.9 Hz, H-2), 5.07 (dd, J2,3 = 9.9, J3,4 = 3.4
Hz, H-3), 4.56 (d, 1H, J1,2 = 9.9 Hz, H-1), 4.27-3.96 (m, 3H, H-5,
H-6a, H-6b), 2.17, 2.09, 2.04, 1.98 (4s, 12H, 4 CH3CO). 13C NMR
(50.3 MHz, Cl3CD) δ = 170.7, 170.3, 70.2, 170.0 (4 COCH3), 88.7
(C-1), 74.9, 72.0, 67.8, 67.2 (C-5, C-3, C-2, C-4), 61.0 (C-6), 20.8,
20.7, 20.6, 20.5 (4 COCH3).
Perfluorobutyl)(phenyl)sulfane 1
[14]: Yield: 80 %.
Isolated and purified mass obtained: 10 mg. TLC (Hexane): Rf =
0.75.
1H-NMR (600 MHz, Cl3CD) δ : 7.66 (d, 2H, J = 7.4 Hz), 7.51 (t,
1H, J = 7.5 Hz), 7.43 (t, 2H, J = 7.5 Hz). 13C NMR (150 MHz,
Cl3CD) δ : 137.6, 131.2, 129.6, 122.9. 19F NMR (564.603 MHz,
Cl3CD) δ : -81.0 (t, 3F), -87.1 (m, 2F), -120.1 (m, 2F), -125.5 (m,
2F)
Methyl 2,3,4-tri-O-acetyl-1-thio-β-D-glucopyranosyluronate,
5
H3COOC
O
AcO
AcO
SH
OAc
2-((perfluorobutyl)thio)etanol 2
[9]: Yield: 75 %.
Isolated and purified mass obtained: 12 mg. TLC (AcOEt:
Hexane 1:1 v/v): Rf = 0.7.
Methyl
2,3,4-tri-O-acetyl-1-thio-β-D-glucopyranosyluronate
was obtained as previously described[41] and showed the same
properties as reported. Briefly, methyl (2,3,4-tri-O-acetyl-D-
glucopyranosyl) uronate bromide was first reacted with
potassium thioacetate in acetone to yield the 1-thioacetyl
derivative which upon treatment with sodium methoxide, at
−45 °C, provided the corresponding glucuronyl 1-thiol.
1H-NMR (600 MHz, Cl3CD) δ : 3.89 (t, 2H, J = 6.1 Hz), 3.14 (t,
2H, J = 6.1 Hz), 1.97 (bs, 1H). 13C NMR (150 MHz, Cl3CD) δ :
61.6, 31.7. 19F NMR (564.603 MHz, Cl3CD) δ : -81.0 (t, 3F), -87.0
(m, 2F), -120.7 (m, 2F), -125.5 (m, 2F).
1H-NMR (200 MHz, Cl3CD) δ = 5.28-5.16 (m, 2H, H-3, H-4), 4.98
(t, 1H, J2,3 = J1,2 = 9.6 Hz, H-2), 4.57 (t, 1H, J1,2 = J1,SH = 9.9 Hz, H-
1), 4.04 (d, 1H, J4,5 = 9.8 Hz, H-5), 3.75 (s, 3H, OCH3), 2.38 (d,
1H, J1,SH = 9.9 Hz, SH), 2.07, 2.01 (2×) (3s, 9H, 3 CH3CO). 13C
NMR (50.3 MHz, Cl3CD) δ = 169.7, 169.5, 169.3 (3 COCH3),
166.7 (COOCH3), 79.0 (C-1), 76.6, 73.3, 72.7, 69.3 (C-5, C-3, C-2,
C-4), 53.0 (OCH3), 20.7, 20.6, 20.5 (3 COCH3).
Methyl 2-((tert-butoxycarbonyl)amino)-3-
6
((perfluorobutyl)thio)propanoate,[ ] 4: Yield: 25 %. Isolated and
purified mass obtained: 10 mg. TLC (AcOEt: Hexane 4:6 v/v): Rf
= 0.8.
1H-NMR (500 MHz, Cl3CD) δ : 5.37 (d, 1H, J =6.2 Hz), 4.63 (d,
1H, J = 5.5 Hz), 3.79 (bs, 3H), 3.53 (dd, 1H, J = 13.6 Hz, 4 Hz),
3.36 (dd, 1H, J = 13.7 Hz, 4.5 Hz), 1.44 (bs, 9H). 13C NMR (150
MHz, Cl3CD) δ : 170.2, 164.4, 155.0, 131.4, 80.8, 53.2, 53.1,
31.1, 28.3. 19F NMR (564.603 MHz, Cl3CD) δ : -81.0 (t, 3F), -86.7
(m, 2F), -120.5 (m, 2F), -125.5 (m, 2F).
2,2’,3,3’,4’,6,6’-hepta-O-acetyl-1-thio-β-D-cellobiose
9
OAc
OAc
O
O
AcO
AcO
O
SH
1
1'
AcO
OAc
OAc
1H-NMR (500 MHz, Cl3CD) δ = 5.15 (t, 1H, J2,3 = J3,4 = 9.3 Hz, H-
3), 5.13 (t, 1H, J2’,3’ = J3’,4’ = 9.4 Hz, H-3’), 5.05 (dd, 1H, J3’,4’ = 9.4,
J4’,5’ = 9.9 Hz, H-4’), 4.91 (dd, 1H, J1’,2’ = 8.1, J2’,3’ = 9.4 Hz, H-2’),
4.88 (dd, 1H, J2,3 = 9.3, J1,2 = 9.9 Hz, H-2), 4.51 (d, 1H, J1,2 = 9.9
Perfluorobutyl
2,3,4-tri-O-acetyl-1-thio-β-D-
methylglucopyranosyluronate,
6
H3COOC
O
4'
F2
C
2'
1'
AcO
S
3'
CF3
1
Hz, H-1), 4.49 (d, 1H, J1’,2’ = 8.1 Hz, H-1’), 4.47 (dd, 1H, J5,6a
=
AcO
C
C
F2
OAc
F2
2.0, J6a,6b = 12.1 Hz, H-6a), 4.36 (dd, 1H, J5,6a’ = 4.4, J6a’,6b’ = 12.5
Hz, H-6a’), 4.08 (dd, 1H, J5,6b = 5.3, J6a,6b = 12.1 Hz, H-6b), 4.03
Yield: 75 %. Isolated and purified mass obtained: 21 mg. TLC
(dd, 1H, J5,6b’ = 2.2, J6a’,6b’ = 12.5 Hz, H-6b’), 3.77 (dd, 1H, J3,4
=
(AcOEt: Hexane 4:6 v/v): Rf = 0.7.
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1H-NMR (600 MHz, Cl3CD) δ = 5.33, 5.22 (2dd, 2H, J = 9.9, J = (C-2’), 69.6 (C-2), 67.9 (C-4’), 62.0 (C-6), 61.7 (C-6’), 20.8, 20.7,
8.9 Hz, H-3, H-4), 5.08 (dd, 1H, J2,3 = 9.9, J1,2 = 10.2 Hz, H-2), 20.6 (7 COCH3). 19F NMR 470.592 Cl3CD) δ = -80.9 (t, J = 9.7 Hz,
5.04 (d, 1H, J1,2 = 10.2 Hz, H-1), 4.09 (d, 1H, J4,5 = 9.9 Hz, H-5), 3H, CF3), -85.8, -88.8 (2 brd, 2F, J = 242.0 Hz, C1’F2), -120.0, -
3.77 (s, 3H, OCH3), 2.06, 2.03 (2×) (3s, 9H, 3 CH3CO). 13C NMR 121.2 (2 dt, 2F, J= 8.5, J = 294.6 Hz, C2’F2), -125.5 (t, 2F, J = 13.0
(150.9 MHz, Cl3CD) δ = 170.0, 169.4, 169.3 (3 COCH3), 166.4 Hz, C3’F2). HRMS (ESI) : m/z [M+H]+ calcd for C30H36F9O17S:
(COOCH3), 80.8 (C-1), 76.4, 72.7, 69.1, 69.0 (C-5, C-3, C-2, C-4), 871.1451, found: 871.1456.
53.2 (OCH3), 20.7, 20.6, 20.5 (3 COCH3). 19F NMR δ = 470.592
Cl3CD) δ = -80.9 (t, J = 9.4 Hz, 3H, CF3), -85.6, -88.2 (2 brd, 2F, J
= 240.0 Hz, C1’F2), -120.4, -121.0 (2 dt, 2F, J = 8.1, J = 294.4 Hz,
C2’F2), -125.5 (t, 2F, J = 12.8 Hz, C3’F2). HRMS (ESI): m/z [M+H]+
calcd for C17H17F9NaO9S: 591.03418, found: 591.03342.
2-((perfluorobutyl)thio)aniline 11[22]: Yield: 90 %.
Isolated and purified mass obtained: 15 mg. TLC (CH2Cl2: iso-
octane 1:1 v/v): Rf = 0.6
Perfluorobutyl
2,3,4,6-tetra-O-acetyl-1-thio-β-D-
galactopyranoside,
8
1H-NMR (600 MHz, Cl3CD) δ : 7.47 (d, 1H, J = 8.6 Hz), 7.28 (t,
1H, J = 8.2 Hz), 6.78 (d, 1H, J =8.1 Hz), 6.74 (t, 1H, J = 7.8 Hz),
4.45 (s, 2H). 13C NMR (150 MHz, Cl3CD) δ : 151.1, 140.0, 133.4,
118.8, 115.8, 104.5. 19F NMR (564.603 MHz, Cl3CD) δ : -81.1 (t,
3F), -87.1 (t, 2F), -120.4 (m, 2F), -125.5 (m, 2F).
Yield: 83 %. Isolated and purified mass obtained: 30 mg. TLC
(AcOEt: Hexane 1:1 v/v): Rf = 0.6
1H NMR (600 MHz, Cl3CD) δ = 5.44 (d, 1H, J3,4 = 2.8Hz, H-4),
5.25 (t, 1H, J2,3 = J1,2 = 10.0 Hz, H-2), 5.10 (dd, J3,4 = 3.3, J2,3
=
(4-methyl-1,2-
phenylene)bis((perfluorobutyl)sulfane) 13: Yield: 50 %. Isolated
10.0 Hz, H-3), 4.99 (d, 1H, J1,2 = 10.0 Hz, H-1), 4.16 (dd, 1H, J5,6a
= 7.2, J6a,6b = 11.4 Hz, H-6a), 4.10 (dd, 1H, J5,6b = 5.9, J6a,6b = 11.4 and purified mass obtained: 8 mg. TLC (Hexane): Rf = 0.6
Hz, H-6b), 4.00 (dd, 1H, J5,6a = 7.2, J5,6b = 5.9 Hz, H-5), 2.16,
1H-NMR (500 MHz, Cl3CD) δ : 7.78 (d, 1H, J = 8.0 Hz), 7.72 (bs,
2.07, 2.03, 1.99 (4s, 12H, 4 CH3CO). 13C NMR (150.9 MHz,
1H), 7.37 (cplx d, 1H, Jo = 8 Hz, Jm = 2Hz, JH-F5 = 0.7 Hz), 2.44 (s,
Cl3CD) δ = 170.5, 170.2, 169.9, 169.6 (4 COCH3), 81.3 (C-1),
3H). 13C NMR (125.721 MHz, Cl3CD) δ : 143.2, 140.3, 139.6,
75.2, 71.7, 67.0, 66.5 (C-5, C-3, C-2, C-4), 61.4 (C-6), 20.7, 20.6
(3×) (4 COCH3). 19F NMR (470.592 MHz, Cl3CD) δ = -81.0 (t, J =
133.0, 130.8, 127.3, 21.3. 19F NMR (470.585 MHz, Cl3CD) δ : -
9.5 Hz, 3H, CF3), -85.8, -88.9 (2 brd, 2F, J = 241.0 Hz, C1’F2), -
81.0 (c, 6F), -86.3 (dt, 4F), -120.4 (m, 4F), -125.6 (m, 4F). HRMS
(ESI): m/z [M+H]+ calcd for C15H7F18S2: 592.9623, found:
120.3, -121.2 (2 dt, 2F, J = 8.4, J = 294.3 Hz, C2’F2), -125.5 (t, 2F,
13.2 Hz, C3’F2). HRMS (ESI): m/z [M+H]+ calcd for
C18H19F9NaO9S: 605.04983, found: 605.04978.
592.9641.
J
=
NH2
N
Perfluorobutyl
2,2’,3,3’,4’,6,6’-hepta-O-acetyl-1-thio-β-D-
N
SC4F
9 2-((perfluorobutyl)thio)pyrimidin-4-amine, 15
:
cellobioside, 10
Yield: 48 %. Isolated and purified mass obtained: 38 mg. TLC
(AcOEt: MeOH + I Acetic Acid 9:1 v/v): Rf = 0.8
1H-NMR (600 MHz, Cl3CD) δ : 8.00 (d, 1H, J = 5.9 Hz), 7.34 (bs,
2H), 6.37 (d, 1H, J = 5.9 Hz). 13C NMR (150 MHz, Cl3CD) δ :
163.7, 161.8, 155.6, 104.4. 19F NMR (564.603 MHz, Cl3CD) δ : -
80.7 (t, 3F), -87.6 (t, 2F), -120.1 (m, 2F), -125.3 (m, 2F). HRMS
(ESI): m/z [M+H]+ calcd for C8H5F9N3S: 345.9982, found:
345.9896.
Yield: 50 %. Isolated and purified mass obtained: 20 mg. TLC
(AcOEt: Hexane 1:1 v/v): Rf = 0.6
1H NMR (600 MHz, Cl3CD) δ = 5.23 (t, 1H, J2,3 = J3,4 = 9.0 Hz, H-
3), 5.14 (t, 1H, J2’,3’ = J3’,4’ = 9.4 Hz, H-3’), 5.05 (dd, 1H, J3’,4’ = 9.4
Hz, J4’,5’ = 10.0 Hz, H-4’), 4.98 (dd, 1H, J2,3 = 9.0, J1,2 = 10.0 Hz, H-
2), 4.95 (d, 1H, J1,2 = 10.0 Hz, H-1), 4.92 (dd, 1H, J2’,3’ = 9.4 Hz,
J1’,2’ = 8.0 Hz, H-2’), 4.49 (d, 1H,J1’,2’ = 8.0 Hz, H-1’), 4.46 (dd, 1H,
J5,6a = 2.0 Hz, J6a,6b = 12.0 Hz, H-6a), 4.35 (dd, 1H, J5’,6a’ = 4.5 Hz,
3-((perfluorobutyl)thio)-5H-
[1,2,4]triazino[5,6-b]indole 17: Yield: 50 %. Isolated and
purified mass obtained: 10 mg. TLC (AcOEt: Hexane 1:1 v/v): Rf
= 0.8
J
6a’,6b’ = 12.4 Hz, H-6a’), 4.12 (dd, 1H, J5,6b = 6.1 Hz, J6a,6b = 12.0
Hz, H-6b), 4.03 (dd, 1H,J5’,6b’ = 2.0 Hz, J6a’,6b’ = 12.4 Hz, H-6b’),
3.76 (dd, 1H, J3,4 = 9.0 Hz, J4,5 = 10.0 Hz, H-4), 3.70-3.65 (m, 2H,
H-5, H-5’), 2.10, 2.08, 2. 06, 2.03, 2.02, 2.01, 1.98 (7s, 21H, 7
CH3CO). 13C NMR (150.9 MHz, Cl3CD) δ = 170.5, 170.3, 170.2,
169.7, 169.6, 169.4, 169.2 (7 COCH3), 100.9 (C-1’), 80.7 (C-1),
77.3 (C-5), 76.2 (C-4), 73.2 (C-3), 73.0 (C-3’), 72.2 (C-5’), 71.7
1H-NMR (600 MHz, Cl3CD) δ : 8.42 (d, 1H, J = 7.8 Hz), 7.80 (t,
1H, J = 8.3 Hz), 7.66 (d, 1H, J = 8.2 Hz), 7.52 (t, 1H, J = 7.9 Hz).
13C NMR (150 MHz, Cl3CD) δ : 158.2, 146.5, 143.1, 141.4,
8 | J. Name., 2012, 00, 1-3
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132.3, 123.1, 122.4, 116.9, 113.1. 19F NMR (564.603 MHz, heteroaromatic sulfides, etc. This convenient, high-yielding
Cl3CD) δ : -80.4 (t, 3F), -86.3 (m, 2F), -119.8 (m, 2F), -125.1 (m, and metal-photoorganocatalyst-free strategy outperforms
2F). HRMS (ESI): m/z [M+H]+ calcd for C13H6F9N4S: 421.0091, traditional near-UV photocatalytic methods while operating
found: 421.0045.
under visible light and in the presence of only an additive
(TMEDA).
We must remark that caution has to be exercised when
employing RFI and TMEDA, since traces of iodine in the
reagents (i.e.: RFI) can form a stable complex with TMEDA
which could be responsible for the radical initiation process
upon visible light irradiation.
2-((perfluorobutyl)thio)benzo[d]thiazole
29
19[ ]: Yield: 99 %. Isolated and purified mass obtained: 23 mg.
TLC (CHCl3: iso-octane: MeOH 0.8:1: 0.2 v/v): Rf = 0.85
In summary, we came up, serendipitously, with a convenient
radical initiator made up of TMEDA / and in-situ iodine present
in RFI, which is capable of triggering the perfluoroalkylation of
organic thiols.
1H-NMR (500 MHz, Cl3CD) δ : 8.17 (cplx d, 1H, J = 8.2 Hz, 0.7
Hz), 7.92 (cplx d, 1H, J = 8.1 Hz, 0.7 Hz), 7.58 (m, 1H, J = 8.3 Hz,
1.2 Hz), 7.52 (m, 1H, J = 7.2 Hz, 1.3 Hz). 13C NMR (125.721
MHz, Cl3CD) δ : 153.4, 150.0, 138.7, 127.2, 127.1, 124.6, 121.5.
19F NMR (470.585 MHz, Cl3CD) δ : -80.9 (t, 3F), -85.2 (t, 2F), -
119.8 (m, 2F), -125.5 (m, 2F). HRMS (ESI):m/z [M+H]+ calcd for
C11H5F9NS2: 385.9641, found: 385.9625.
Acknowledgements
Thanks are given to financial agencies: Universidad de Buenos
Aires and CONICET. SBV, MLU and AP are research members of
CONICET. DEY, AEC, MEC are Conicet doctoral Scholarship
holders. We also thank Dr Lucas Fabian for acquiring NMR
data.
2-((perfluorooctyl)thio)benzo[d]thiazole 20
Yield: 50 %. Isolated and purified mass obtained: 10 mg. TLC
(CHCl3: iso-octane: MeOH 0.8:1: 0.2 v/v): Rf = 0.75
:
1H-NMR (600 MHz, Cl3CD) δ : 8.18 (d, 1H, J = 8.2 Hz), 7.92 (d,
1H, J = 8.0 Hz), 7.58 (t, 1H, J = 7.2 Hz), 7.52 (t, 1H, J = 8.01 Hz).
13C NMR (150 MHz, Cl3CD) δ : 157.7, 153.4, 138.7, 127.2,
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A simple and metal-/ photoorganocatalyst-free strategy has
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•
•
relevant targets such as cysteine derivatives, thioaldoses,
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