Transition-Metal-Free and Visible-Light-Mediated Desulfonylation and Dehalogenation Reactions: Hantzsch Ester Anion as Electron and Hydrogen Atom Donor

Article abstract of DOI:10.1021/acs.joc.0c01523

Novel approaches for N- and O-desulfonylation under room temperature (rt) and transition-metal-free conditions have been developed. The first methodology involves the transformation of a variety of N-sulfonyl heterocycles and phenyl benzenesulfonates to the corresponding desulfonylated products in good to excellent yields using only KO^tBu in dimethyl sulfoxide (DMSO) at rt. Alternately, a visible light method has been used for deprotection of N-methyl-N-arylsulfonamides with Hantzsch ester (HE) anion serving as the visible-light-absorbing reagent and electron and hydrogen atom donor to promote the desulfonylation reaction. The HE anion can be easily prepared in situ by reaction of the corresponding HE with KO^tBu in DMSO at rt. Both protocols were further explored in terms of synthetic scope as well as mechanistic aspects to rationalize key features of desulfonylation processes. Furthermore, the HE anion induces reductive dehalogenation reaction of aryl halides under visible light irradiation.

Full text of DOI:10.1021/acs.joc.0c01523

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Article
TRANSITION-METAL-FREE AND VISIBLE LIGHT MEDIATED
DESULFONYLATION AND DEHALOGENATION REACTIONS: HANTZSCH
ESTER ANION AS ELECTRON AND HYDROGEN ATOM DONOR
Micaela D. Heredia, Walter Damian Guerra, Silvia Maricel Barolo, Santiago
José Fornasier, Roberto Arturo Rossi, and María E. BUDEN
J. Org. Chem., Just Accepted Manuscript • DOI: 10.1021/acs.joc.0c01523 • Publication Date (Web): 06 Sep 2020
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TRANSITION-METAL-FREE AND VISIBLE LIGHT MEDIATED
DESULFONYLATION AND DEHALOGENATION REACTIONS: HANTZSCH
ESTER ANION AS ELECTRON AND HYDROGEN ATOM DONOR
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Micaela D. Heredia,a Walter D. Guerra,a Silvia M. Barolo,a Santiago J. Fornasier,a Roberto A.
Rossia and María E. Budén a*
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aINFIQC, Facultad de Ciencias Químicas, Universidad Nacional de Cꢀrdoba, X5000HUA
Cꢀrdoba, Argentina
TOC
Abstract
Novel approaches for N and O-desulfonylation under room temperature (rt) and transition-
metal-free conditions have been developed. The first methodology involves the transformation
of a variety of N-sulfonyl heterocycles and phenyl benzenesulfonates to the corresponding
desulfonylated products in good to excellent yields using only KOtBu in DMSO at rt.
Alternately, a visible light method has been used for deprotection of N-methyl-N-
arylsulfonamides with Hantzsch ester (HE) anion serving as visible light absorbing reagent and
electron and hydrogen atom donor to promote the desulfonylation reaction. HE anion can be
easily prepared in situ by reaction of the corresponding HE with KOtBu in DMSO at rt. Both
protocols were further explored in terms of synthetic scope as well as mechanistic aspects in
order to rationalize key features of desulfonylation processes. Furthermore, HE anion induces
reductive dehalogenation reaction of aryl halides under visible light irradiation.
Keywords: Desulfonylation, Dehalogenation, Visible Light, Hantzsch ester (HE)
Introduction
Many protecting groups were developed for amine functionality and provide desired
stability towards acid, basic, reducing or oxidizing conditions.1,2 In particular, sulfonamides as
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nitrogen protecting groups play an important role in amine chemistry.3 For instance, benzene
sulfonyl or p-toluenesulfonyl (tosyl, Ts) groups are easy to introduce offering extreme
robustness and high crystallinity helping in the compound purification.1 However, drastic
conditions are required to remove sulfonyl groups and, consequently, several methodologies to
promote desulfonylation reactions have been described. Deprotection methods can be classified
into three large families: acidic reductive conditions, reductions in strongly basic media or
electron transfer (ET) cleavage.
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The cleavage of N-S bond can be acid-mediated by HBr,4–6 HCl,7 H2SO4,7,8 CF3COOH,9
CF3SO3H,10 HF-pyridine with anisole11 or CH3COOH/HClO4 mostly in very harsh conditions
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or at high temperatures. Moreover, N-deprotection method using HBr requires a bromine
scavenger such as phenol4 to avoid monobromination and/or dibromination of the aromatic ring
of aniline.
Likewise, many methods using strong bases or nucleophiles are well known, such as
NaOH or KOH in MeOH,13,14 KOH in THF/H2O mixture,15 NaOtBu in dioxane,16 thioglycolate
in DMF,17 Cs2CO3 in THF/MeOH,18 PhMe2SiLi in THF,19 sodium bis(2-
methoxyethoxy)aluminum hydride in benzene or toluene as solvents20 and n-Bu4NF21 in dry
THF. Despite the large number of N-desulfonylation methodologies in basic media, only a few
are useful in industries due to long time reactions and high temperatures are required to obtain
the corresponding desulfonylated products. In some cases, a phase transfer catalyst such as
cetyltrimethylammonium bromide is needed due to the low solubility of the amines in the
media. The use of MeOH is discouraged by its toxicity and production of toxic methyl p-
toluenesulfonate as byproduct, as consequence of esterification of p-toluensulfonic acid
liberated during the reaction. Moreover, Cs2CO3 in MeOH produces an N-methylated impurity
that is difficult to remove during purification processes18 and also, NaOH at reflux in EtOH led
to degradation products.22
Desulfonylation induced by ET is also widely described. The most common approaches
of this type of reductions are promoted by SmI2,23–28 Mg/MeOH,29–33 alkali metals,34–39 low-
valent titanium,40,41 organic electron donors42–44 and electrochemistry.45–48 In particular,
photoinduced ET (PET) has also been applied for desulfonylation reactions.49 PET process
under UV irradiation using 2-phenyl-N,N´-dimethylbenzimidazoline as electron and hydrogen
donor has been used in tosyl amides deprotection.50 N-sulfonyl indoles can be deprotected by a
PET reaction with NEt3 serving as both an electron and proton donor and n-Bu3SnH as a
hydrogen atom donor.51 In 2013, Xiao et al. reported N-detosylation of tosyl amides using
visible light and iridium as photocatalysts with Hantzsch ester (HE, diethyl 2,6-dimethyl-1,4-
dihydropyridine-3,5-dicarboxylate) as electron donor.52 Moreover, in 2018, Hasegawa and co-
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workers demonstrated that benzimidazolium naphthoxide betaine and 1,3-dimethyl-2-
hydroxynaphthylbenzimidazoline (HONap-BIH) can serve as light absorbing, electron and
hydrogen atom donor for desulfonylation of N-sulfonyl-amides and amines.53,54 Another study
of Hasegawa has reported a new visible-light-promoted system for desulfonylation process
consisting of benzimidazolium aryloxide betaines (BI+_ ArO–) and stoichiometric hydride
reducing reagents.55 More recently, a visible light protocol using Cu complex/HE has just been
developed in order to deprotect N-heterocycles.56 Finally, an acridine radical as a single-electron
reductant has been also used for desulfonylation reactions.57 However, all these recent visible
light protocols use expensive photocatalysts or even catalysts that are not commercially
available.
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Over the past few years Hantzsch esters (HEs) were extensively used in hydrogen
transfer reactions.58 Additionally, with the continuous advances in visible light photocatalysis
field,59–61 HEs have also been used as electron donor and proton source in a large number of
photoredox processes.62 In this sense, a wide range of organic transformations involve the use of
transition-metal photocatalysts in combination with HEs as reductants.63–68 Other recent reports
demonstrated the formation of an electron donor-acceptor (EDA) complex between HE and N-
alkoxyl derivatives, N-acyloxyphthalimides, N-alkyl-pyridinium salts or heteroaryl N-oxides to
undergo PET in absence of a photocatalyst under visible light irradiation.69–72 Furthermore, HE
in the presence of base was recently used as visible light catalyst to obtain alkenes and diaryl
sulfinates.73,74
In this context, the development of a convenient, practical and more economical method
to cleavage N-S bonds avoiding the use of high temperatures, harmful solvents and expensive
transition-metal catalysts is highly desired. Herein, we describe two efficient transition-metal-
free protocols whose application is related to the nature of the sulfonamide moiety. KOtBu in
DMSO at rt provides a clean approach for deprotection of N-sulfonyl heterocycles and phenyl
benzenesulfonates.53 However, for N-methyl-N-arylsulfonamides a stronger reductive method
for an effective desulfonylation is needed. Thus, the use of the anion of HE to promote the
deprotection of N-methyl-N-arylsulfonamides under visible light irradiation was explored. In
this work HE anion is easily prepared in situ by reaction of the commercial HE with KOtBu in
DMSO. Additionally, HE anion absorbs light in visible region; hence this protocol does not
require a transition metal photocatalyst or an absorbing light complex.
Finally, mechanistic insights were explored in order to understand the difference in
reactivity and the mechanisms involved. The scope of these two methods of N-S (or O-S)
cleavage were successfully examined using a large variety of N-sulfonyl heterocycles, N-
sulfonylamines and even phenyl benzenesulfonates. Furthermore, the use of HE anion as visible
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light absorbing reagent was studied in the reduction of several aryl and heteroaryl halides (RX)
including iodide, bromide and chloride derivatives.
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Results
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N-tosylated indole 1a was selected as model substrate to optimize our N-desulfonylation
reaction conditions. As summarized in Table 1, 2a was obtained in 49% yield when the reaction
was carried out in DMF for 1 h, using three equivalents of KOtBu at rt (Table 1, entry 1).
Notably, yield was increased to 96% when DMSO was employed as solvent (entry 2). A variety
of solvents revealed that the reaction media had a significant impact on the reaction efficiency.
THF and ethanol did not work well for this desulfonylation process, and 2a was obtained in
26% yield and traces, respectively after 1 h (entries 3 and 4). Incomplete conversion was
observed when the amount of KOtBu was lowered (entry 5). Base effect was also examined
(entries 6-11) founding that the reaction did not work using K2CO3, Cs2CO3 or KOH at rt and
only 12% yield of 2a was obtained when the reaction was carried out with KOH at 65 ºC.13
Moreover, 21% and 84% yields of 2a were obtained when other bases such as NaH and NaOtBu
were employed. This environmentally friendly methodology avoided the use of transition-
metal56 or phase transfer catalysts,15 toxic solvents and high temperature conditions.13
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Table 1. N-Desulfonylation reaction of N-indole 1aa
Entry
Conditionsa
Yields 2ab
49
96 (91c)
26
< 5
48
--
--
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3 equiv. KOtBu, DMF
3 equiv. KOtBu, DMSO
3 equiv. KOtBu, THF
3 equiv. KOtBu, EtOH
1.1 equiv. KOtBu, DMSO
3 equiv. K2CO3, DMSO
3 equiv. Cs2CO3, DMSO
3 equiv. KOH, DMSO
3 equiv. KOH, 65 °C, DMSO
3 equiv. NaH, DMSO
3 equiv. NaOtBu, DMSO
--
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21
84
aThe reaction was carried out under N2 atmosphere using 1a (1 equiv, 0.1 mmol)
and base in 1 mL of solvent and the mixture was protected from light with
b
aluminum foil. Yields were quantified by GC using internal standard method.
cIsolated yield.
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Once optimal reaction conditions were determinated, several heterocycles were
deprotected using only KOtBu in DMSO at rt. Results are shown in Table 2. A complete N-
desulfonylation of N-tosyl 7-azaindole (1b), benzotriazole (1c) and pyrrole (1d) was achieved
after 1 h (entries 1-3) whereas only 47% yield of carbazole was obtained under identical
condition (entry 4). Other sulfonyl protecting groups were tested such as benzenesulfonyl, 2-
chlorobenzenesulfonyl and 2-nitrobenzenesulfonyl (o-Ns) groups (substrates 1f-1h) and
desulfonylated product 2a was also obtained in very good yields (entries 5-7). Additionally,
desulfonylation reaction of compound 1f was carried out at higher concentrations in order to
demonstrate the practical utility of this methodology. Product 2a was successfully obtained
without a decrease in the isolated yield when 0.5 mmol of 1f in DMSO were employed or even
when the reaction was scaled-up to 1 gram (3.9 mmol, entry 5).
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Table 2. N-Desulfonylation of indoles and related heterocyclesa
Yield
Entry
Substrate
Product
(%)b
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87
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3
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99
47 (1 h)
48 (3 h)c
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5
91, 88,d
86e
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aThe reaction was carried out under N2 atmosphere using 1 (1 equiv, 0.1 mmol) and KOtBu (3
equiv) in DMSO (1 mL) and the mixture was protected from light with aluminum foil.
bIsolated yields after column chromatography. N-tosylcarbazole (1e) was recuperated in 50%
yield. Reaction carried out 5 times more concentrated (0.5 mmol of 1f in 1 mL of DMSO).
eReaction carried out starting from 1gram of 1f in 7.8 mL.
c
d
Next, our attention was focused on the scope of this desulfonylation process to deprotect
different N-arylsulfonamides and phenyl benzenesulfonates. For instance, N,N-diphenyl
tosylamine (1i) was chosen as representative derivative of aromatic p-toluenesulfonamides
giving the desufonylted product 2i in 72% yield (Table 3, entry 1). However, N,N-diphenyl
benzenesulfonamide (1j) and unsubstituted or N-methylsubstituted aromatic sulfonamides (1k
and 1l) did not give the corresponding products 2j, 2k or 2l (Table 3, entries 2-4). These results
led us to explore the possibility of carrying out selectively the removal of p-toluenesulfonyl
group. In this way, the polytosylated substrate 1m was tested and benzenesulfonate moiety
could be selectively deprotected in presence of p-toluenesulfonamide moiety, giving 2m in
moderate isolated yield (entry 5). There are few examples of removing sulfonyl groups from
sulfonates such as KOH in refluxing MeOH,75 KOH with tBuOH in toluene at 100 °C,76 n-PrSLi
in HMPA at 180 °C77 or by using photochemical process via PET.78,79 Thus, other
benzenesulfonate substrates were studied following our protocol such as 4-methoxyphenyl 4-
methylbenzenesulfonate (1n), 4-cyanophenyl 4-methylbenzenesulfonate (1o), 2-iodophenyl 4-
methylbenzenesulfonate (1p) and 2-iodophenyl benzenesulfonate (1q) giving the corresponding
phenols 2n-p in very good yields (74-89%) and using only KOtBu in DMSO at rt.
Table 3. N-Detosylation of amino and sulfonate moietya
Entry
Substrate
Product
Yield (%)b
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72
--
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--
10
5c
44 c,d
6
7
74 (75)c
89 (90)c
8
88 (93)c
9
80
aThe reaction was carried out under N2 atmosphere using 1 (1 equiv, 0.1 mmol) and
KOtBu (3 equiv) in DMSO (1 mL) and the mixture was protected from light with
aluminium foil. bYields were quantified by GC using internal standard method.
cIsolated yield. dUsing 5 equiv. of KOtBu for 3 h.
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A plausible mechanism for the desulfonylation reaction, which is consistent with the
observations described above, is shown in Scheme 1. Although the pKa (methyl group) of
toluensulfonamide is unknown, it can be approximated to that of 1-methyl-4-
(phenylsulfonyl)benzene (5), whose pKa is 29.880 in DMSO. Therefore, the N-tosylsulfonamide
forms the corresponding anion 3 in the presence of KOtBu (tBuOH, pKa=32.2),81 which was
indicated by the observation that the solution turned to blue. The N-S bond of anion 3 could
fragment to produce amide anion 4, which after protonation finally gives the deprotected
product 2. This fragmentation is thermodynamically controlled by the acidity (pKa value) of the
final deprotected product 2. Since the conjugate base of compound 5 is more basic than those of
indole (pKa= 21.0 in DMSO)82 and diphenyl amine (pKa= 25.0 in DMSO),83 this process is
favored for N-tosyl indole (1a) and diphenyl N-tosylamine (1i). Meanwhile, for N-methyl-N-
phenyltosylamine (1l) this fragmentation does not take-place due to the higher pKa value for N-
methyl-N-phenylamine (pKa= 30.6 for aniline in DMSO).83
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Scheme 1. Possible mechanism of N-detosylation reactions in basic medium
A different mechanism for the deprotection of N-benzenesulfonamides is proposed
involving a direct attack of the base to the sulfur atom (Scheme 2). This behavior explains the
reactivity of 1f-h with phenyl, 2-chlorophenyl and 2-nitrophenyl as substituents. This
mechanism could also explain the lack of reactivity for N,N-diphenyl benzenesulfonamide (1j)
due to a high steric hindrance for the nucleophilic attack of the base.
Scheme 2. Possible reaction mechanism for deprotection of N-benzenesulfonamides
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In order to demonstrate the presence of a polar mechanism, the reaction of 1a was
quenched with benzyl bromide and benzyl indole (2q) was obtained in quantitative isolated
yield (eq 1). In addition, the reaction of 1a with KOtBu was carried out in presence of 2,2,6,6-
tetramethyl-1-piperidinyloxy (TEMPO) as a radical trapping and similar yield of 2a was
obtained (87% yield) indicating the absence of radicals as intermediates (eq 2).
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Regarding to the lack of reactivity of 1j and 1l substrates under proposed polar
mechanism (Table 3, entries 2 and 4), we decided to explore PET for N-desulfonylation
reactions. As dimsyl anion is able to form aryl and alkyl radicals from RX under visible light
irradiation,84,85 we carried out the reaction for substrate 1j with KOtBu in DMSO under
irradiation using UV-vis lamps ( > 350 nm) for 3 h giving the desulfonylation product 2i in
65% yield (Table 4, entry 1). Moreover, product 2i was obtained in 88% yield when UV-vis
lamps were replaced by using 3W blue light-emitting diodes (LEDs) (entry 2). In order to rule
out homolytic fragmentation, photoinduced reaction was performed in absence of base and
substrate 1j was recovered in quantitative yield (entry 3). When same conditions were applied to
substrate 1r, the desulfonylated product 2l was given in only 20% yield (entry 4). Probably, the
reduction potential of the excited dimsyl anion (unknown) could not achieve the ET to initiate
the reaction. As some anions of substituted dihydro ethyl benzoates and quinoline previously
prepared in liquid ammonia have been used as hydrogen donors in reductive reactions,86,87 we
proposed HE anion as both an electron and hydrogen atom donor to promote desulfonylation
reaction of N-methyl-N-arylsulfonamides as an alternative strategy to [Ir(ppy)2(dtb-
bpy)PF6]/HE52 and Cu complex/HE.55
Therefore, the reaction of 1r with 1 equiv. of HE and 1.1 of KOtBu for 17 h using blue
LED afforded product 2l in 46% yield (Table 4, entry 5). Furthermore, higher yield was
observed when the reaction was carried out employing 2.2 equiv of KOtBu (73% of 2l, entry 6).
Notably, the yield was increased to 79 and 88% when higher amounts of HE (1.3 and 1.5 equiv)
were used (entries 7 and 8). Finally, product 1r was obtained in 98% yield when 2 equiv of HE
were employed (entry 9). No reaction is detected in dark conditions (entry 10) discarding a
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spontaneous ET or polar mechanism. Moreover, similar yield of 2l was given when the reaction
was carried out in 1 h, reducing considerably the reaction time (entry 11). No product 2l was
obtained in absence of base (entry 12) or when other bases and reducing reagents such as NEt3
or N-ethyldiisopropylamine (DIPEA) were used as control experiments (entries 13-14). Finally,
the desulfonylation was carried out in presence of TEMPO and 1,1-diphenylethylene as radical
scavengers and reaction was partially inhibited (entries 15 and 16). We suggest that radical
formation could be involved in the key step of this mechanism (Scheme 3).
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Table 4. Photodesulfonylation of 1j and 1r in DMSOa
Entry
Substrate
Conditions
Time (h)
Yieldb
1c
3
2i, 65
hnm, KOtBu (3 equiv)
2
3
KOtBu (3 equiv)
Without base
3
3
2i, 88
2i, --
1j
1j
4
KOtBu (3 euiv)
1
2l, 20
1r
1r
1r
1r
HE (1 equiv) KOtBu (1.1 equiv)
HE (1 equiv) KOtBu (2.2 equiv)
HE (1.3 equiv) KOtBu (2.2 equiv)
HE (1.5 equiv) KOtBu (2.2 equiv)
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2l, 46
2l, 73
2l, 79
2l, 88
2l, 98
(95)d
2l, --
1r
HE (2 equiv) KOtBu (2.2 equiv)
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17
1r
1r
1r
1r
1r
1r
DarkHE (2 equiv) KOtBu (2.2 equiv)
HE (2 equiv) KOtBu (2.2 equiv)
 (2 equiv)
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2l, 98
2l, --
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DIPEA (2 equiv)
1
2l, --
t3 (2 equiv)
1
2l, --
1
2l, 77
1,1-diphenylethene (0.5 equiv) 
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HE (2 equiv) KOtBu (2.2 equiv)
TEMPO (30 mol%)HE (2 equiv)
KOtBu (2.2 equiv)
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2l, 68
1r
aUnless otherwise noted, the photostimulated reaction conditions was carried out under N2 atmosphere using
1 (1 equiv, 0.1 mmol), base and/or additive in DMSO (1 mL) with blue-LED (3 W) in a sealed tube. bYields
c
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were quantified by GC using internal standard method. Irradiation was conducted in a photochemical
reactor equipped with two HPIT 400W lamps ( ≥ 350 nm). dIsolated yield.
A proposed mechanism for photoinduced N-desulfonylation reaction in presence of HE
anion is shown in Scheme 3. HE anion is easily prepared in situ by reaction of HE with KOtBu
in DMSO as solvent. Anion formation is rapidly detected due to the color of the solution
(orange) indicating that HE anion is the visible light absorbing reagent (max= 475 nm).88 After
irradiation, ET occurs between the photoexcited HE anion and N-methylarylsulfonylamine 1
forming the corresponding radical anion of the substrate (initial step) and HE radical. The N-S
bond cleavage in these radical anions can generate either N-centered anions or -radicals
depending on the nature of the N-substituent. It is known that N-tosyl-N,N-phenylamine (1i) and
N-benzyl-N-phenyl p-toluensulfonamide fragments to give aminyl radicals (Ph2N• and
–
Ph(Bn)N•)53,43 and sulfonate anions (TolSO2 ) (Step 1). A fast hydrogen transfer from HE anion
to aminyl radical affords product 2 and HE radical anion. Alternatively, sulfonate anion can
deprotonate HE radical to give the corresponding HE radical anion and sulfonic acid. The
driving force for this reaction is the rearomatization of HE anion (or HE radical) to give HE
radical anion (Step 2). Following, ET from HE radical anion to 1 give a pyridine derivative and
N-methylarylsulfonylamides radical anion to continue the radical chain process (Step 3).
Finally, the intermediate aminyl radical can generate the reductive product 2 removing a
hydrogen from HE radical (final step).
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Scheme 3. Proposed photodesulfonylation reaction mechanism using HE anion as visible
light absorbing reagent and electron and hydrogen atom donor
Next, several N-methyl-N-arylsulfonamides (1l and 1s-1ab) were examined under the
same photoinduced conditions in presence of HE anion (Table 5). Desulfonylation reaction
exhibited high functional group tolerance and yields. For orto or para substituted sulfonamides
with electron-donating and electron-withdrawing groups the reaction gives the desired products
in good to excellent yields (51-98 % yields, entries 1-11). Furthermore, similar yields were also
obtained if tosyl or benzenesulfonyl protecting groups were used.
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Table 5. Substrate scope examination of photodesulfonylation reactiona
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Entry
Substrate
Product
Yieldb
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51
2
3
4
5
6
7
95(80)c
98
93c
97 (80)c
98 (90)c
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90 (85)c
aThe photostimulated reaction was carried out under N2 atmosphere using 1 (1 equiv, 0.1 mmol), HE (2
equiv) and KOtBu (2.2 equiv) in DMSO (1 mL) using 3 W blue LED, at rt in a sealed tube. Yields
b
were quantified by GC using internal standard method. cIsolated yields.
For N-(4-iodophenyl)-N-methylbenzenesulfonamide (1aa, Table 5, entry 10), the
dehalogented product 2l was obtained as main product. Regarding to this result and the
mechanism presented in Scheme 4, the formation of radical anion 1aa as intermediate is
proposed (Scheme 4). This radical anion has two possible reaction pathways. First, a C-I bond
fragmentation may occur to give radical 6 which after reduction affords intermediate 7 (Path A).
This intermediate can also react with HE anion under photostimulated conditions to finally yield
the product 2l. The other possibility is a N-S bond fragmentation to give anion 8 which finally
provides product 9 with retention of iodine atom (Path B). In this case, path B was discarded
because 9 was not detected. This result suggests that C-I fragmentation rate giving radical 6 is
faster than N-S fragmentation to give 9. Furthermore, it confirms the presence of radical anions
as intermediates in the proposed photoinduced reaction (Scheme 3). Otherwise, C-I
fragmentation was not observed for substrates 1p-q in the first approach (KOtBu in DMSO at rt,
Table 3, entries 8 and 9) showing an important difference between both examined mechanisms.
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Scheme 4. Possible fragmentations of radical anion 1aa
PET also provides an alternative route for dehalogenation reactions. In recent years,
Pd,89 Ir,90 Cu,91 Pt complex92 and Ni supported on carbon nitride89 have been used to undergo
reductions of aryl halides under visible light irradiation. Particularly, dehalogenation and aryl
radical generation could also be achieved by using many visible light organic photoreductants93–
or photocatalyts.96–102 To further explore our visible-light-promoted method, reduction
95
reaction of aryl or heteroaryl halides in presence of HE anion was studied. As shown in Table 6
aryl chloride, bromide and iodide derivatives are dehalogenated (entries 1-10) in good to
excellent yields under visible light irradiation using HE anion as electron and hydrogen atom
*
donor. We finally suggest that oxidation potential of photoexcited HE anion (Eox HE /HE
-
= -2.490
V)103 is higher than photoexcited dimsyl anion which does not effectively reduce aryl bromides
or chlorides.84,85
Table 6. Photoinduced reduction of ArX with HE aniona
Entry
Substrate
Product
Yieldb
1
81
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a
The photostimulated reaction (1 h) was carried out under N2 atmosphere using 10 (1 equiv, 0.1
mmol), HE (2 equiv) and KOtBu (2.2 equiv) in DMSO (1 mL) using 3 W blue LED, at rt in a sealed
tube. bYields were quantified by GC using internal standard method.
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Conclusions
In order to summarize, in this work we presented two green synthetic methodologies
towards the desulfonylation process under transition-metal-free and rt conditions. First
methodology proceeds under mild reaction conditions using only KOtBu in DMSO at rt where a
variety of N-sulfonyl heterocycles and phenyl benzenesulfonates were effectively deprotected.
This strategy involves a polar mechanism very sensitive to both electronic and steric effects.
Second methodology involves a visible-light-promoted method utilizing HE anion as electron
and hydrogen atom donor and blue LED as a light source. In this way, several N-methyl-N-
arylsulfonamides have given the corresponding products in good to excellent yields.
Furthermore, the reaction was highly tolerant to a variety of functional groups and was
successfully scaled-up to 1 gram. Moreover, this methodology was also expanded to aryl halides
substrates and it is noteworthy that even the ArCl react giving ArH with good yields. HE anion
as visible-light absorbing reagent does not require previous preparation and is a convenient
alternative to expensive transition-metal photocatalysts.
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Experimental Section
General Methods. Purification of desired compounds was made by column chromatography on
silica gel. Gas chromatographic (GC) analysis were performed with a flame-ionization detector,
on 30 m capillary column of a 0.32 mm x 0.25 μm film thickness, with a 5%
phenylpolysiloxane phase. Gas chromatography-mass spectroscopy (GC-MS) analysis were
performed employing an electronic impact (EI) ionization method and a 25 m x 0.2 mm x 0.33
1
μm column with a 5% phenylpolysiloxane phase. H NMR and 13C NMR1H spectra were
recorded on 400 and 500 MHz in spectrometer CDCl3 or Acetone-d6 as solvents with TMS as
internal standard. Additional 19F NMR spectra was performed for fluorinated compounds and
was recorded on 377 MHz in spectrometer CDCl3, Acetone-d6 (CD3COCD3) or DMSO-d6
(CD3S(O)CD3) as solvents. Coupling constants are given in Hz and chemical shifts are reported
in δ values in ppm. Data are reported as followed: chemical shift, multiplicity (s = singlet, s br =
broad singlet, d = doublet, t = triplet, dd = double doublet, dt = double triplet, ddd = double
double doublet, m = multiplet), coupling constants (Hz), and integration. All new products were
1
further characterized by 2D NMR techniques (1H/1H COSY, 1H/13C HSQC and H/13C HMBC)
and high resolution mass spectrometry (HRMS). HRMS analyses were carried out using a time-
of-flight mass spectrometry (TOF-MS) instrument with an electrospray ionization (ESI) source.
Photoinduced reactions were conducted with blue LED (= (465 20) nm) lights performing at
3W of potency and 700 mV of current emission spectra (Figure S1) and HPIT 400W lamps (≥
350 nm, Figure S2). Apparatus and irradiation setup are shown in Figure S3.
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Materials. 1H-Indole (2a), 1H-pyrrolo[2,3-b]pyridine (2b), 1H-benzo[d][1,2,3]triazole
(2c), 1H-pyrrole (2d), 9H-carbazole (2e), N,N-diphenylamine (2i), 4-methoxyphenol (2n), 4-
hydroxybenzonitrile (2o), 2-iodophenol (2p), aniline, benzyl bromide, 4-methoxyaniline, 4-
methylaniline, 4-aminobenzonitrile, 4-(tert-butil)-aniline, [1,1'-biphenyl]-2-amine, 4-
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(trifluoromethoxy)aniline,
4-fluoroaniline,
4-iodoaniline,
4-aminophenol,
3-
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aminoacetophenone, benzenesulfonyl chloride, 2-chlorobenzenesulfonyl chloride, 2-
nitrobenzenesulfonyl chloride, 2-iodonaphtalene (10a), 1-bromonaphtalene (10b), 1-
chloronaphtalene (10c), 9-bromoanthracene (10d), 9-bromophenanthrene (10e), 4-bromo-1,1'-
biphenyl (10f), 3-iodopyridine (10g), 2-chloropyridine (10h), 4-bromobenzonitrile (10i), 4-
chlorobenzonitrile (10j), naphtalene (11a), anthracene (11d), phenanthrene (11e), biphenyl
(11f), pyridine (11g), cyanobenzene (11i), KOtBu, NaOtBu, K2CO3, Cs2CO3, KOH, NaOH, NaH
(60% in mineral oil), NH4NO3, NH4Cl, tetrabutylammonium hydrogensulfate, Na2SO4, 2,2,6,6-
tetramethyl-1-piperidinyloxy (TEMPO), Hantzsch ester, NEt3, DIPEA, 1,1-diphenyl ethene,
pyridine were purchased from commercial suppliers and used without further purification.
DMSO, DMF, THF, CH2Cl2 and toluene were distilled and dried under molecular sieves (3 Å).
All solvents were analytical grade. The silica used in column chromatography corresponds to
silica gel 60 (0.063−0.200 mm).
Typical Procedures for Synthesis of Sulfonamides.
Method A. The reaction was carried out in a Schlenk tube equipped with an inert N2 inlet and
magnetic stirred at rt. In the Schlenk tube, DMSO (5 mL) was dried and deoxygenated, KOtBu
(1.0 equiv, 112 mg, 1 mmol) was added and the mixture was protected from light with
aluminum foil. Then, the corresponding NH-heterocycle or aniline (1 equiv, 1 mmol) and
benzenesulfonyl chloride (1.2 equiv, 1.2 mmol) were added and the reaction mixture was stirred
overnight (18 hours). After the reaction was finished, it was quenched with NH4NO3 or NH4Cl
and water in excess and the residue was extracted with EtOAc or CH2Cl2 (3 x 30 mL), the
organic layers extracted were combined, washed with water, dried with anhydrous Na2SO4 and
concentered under reduced pressure to leave the crude products. The reaction was analyzed with
TLC, GC and isolated with column chromatography over silica gel.
For details of Methods B to E see SI.
Characterization Data of Synthetized Sulfonamides.
1-[(2-Chlorophenyl)sulfonyl]-1H-indole (1g). Titled compound was obtained according to
Method B and was purified by column chromatography on silica gel eluting with hexane/EtOAc
1
(90:10 → 80:20). Light yellow solid was isolated in 71% yield (0.71 mmol, 207 mg). H NMR
(400 MHz, CDCl3) δ 8.15 (dd, J = 8.2, 1.8 Hz, 1H), 7.74 (d, J = 3.7 Hz, 1H), 7.71 - 7.65 (m,
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1H), 7.60 - 7.54 (m, 1H), 7.51 - 7.39 (m, 3H), 7.25 - 7.18 (m, 2H), 6.67 (d, J = 3.7 Hz, 1H). 13C
NMR 1H (101 MHz, CDCl3) δ 136.4, 134.8, 134.5, 132.9, 132.4, 131.2, 130.6, 127.9, 127.2,
124.3, 123.3, 121.5, 113.0, 107.5. 1H/1H COSY NMR (400 MHz, CDCl3) δH/δH 8.15/7.51-7.39,
1
7.74/6.67, 7.71-7.65/7.60-7.54, 7.60-7.54/7.25-7.18, 7.51-7.39/7.51-7.39. H/13C HSQC NMR
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(400 MHz, CDCl3) δH/δC 8.15/131.4, 7.74/127.9, 7.71-7.65/113.0, 7.60-7.54/121.5, 7.51-
7.39/134.8, 7.51-7.39/132.4, 7.51-7.39/127.2, 7.25-7.18/123.3, 7.25-7.18/124.3, 6.67/107.5.
1H/13C HMBC NMR (400 MHz, CDCl3) δH/δC 8.15/132.9, 8.15/134.8, 7.74/107.5, 7.74/130.6,
7.74/134.5, 7.71-7.65/132.4, 7.71-7.65/130.6, 7.60- 7.54/124.3, 7.60-7.54/134.5, 7.51-
7.39/127.2, 7.51-7.39/131.2, 7.51-7.39/132.4, 7.51-7.39/132.9, 7.51-7.39/136.4, 7.25-
7.18/113.0, 7.25-7.18/121.5, 7.25-7.18/130.6, 7.25-7.18/134.5, 6.67/127.9, 6.67/130.6,
6.67/134.5. GC/MS EI m/z 293 (M+ +2, 9), 291 (M+, 22), 117 (10), 116 (100), 111 (27), 90 (11),
89 (61), 75 (35), 63 (37), 51 (10), 50 (17). HRMS (ESI) m/z: [M + H]+ Calcd for C14H11ClNO2S
292.0194; Found 292.0189.
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Methylation of Synthetized Sulfonamides (Method F). The reaction was carried out in a
round-bottom flask equipped with a magnetic stirred bar. KOtBu was added (1.1 equiv) to a
solution of sulfonamide (1 equiv) in DMSO (2 mL) then, iodomethane (3 equiv) was slowly
added. The resulting mixture was stirred at rt overnight. Water was added, the crude was
extracted with EtOAc (3 x 30 mL), and the layers were separated. The organic layers extracted
were combined, washed with water, dried with anhydrous Na2SO4 and concentered under
reduced pressure to leave the crude products. The reaction was analyzed with TLC, GC and
isolated with column chromatography over silica gel.
N-(4-(tert-Butyl)phenyl)-N-methylbenzenesulfonamide (1v) was obtained from 1v-s and was
purified by column chromatography on silica gel eluting with hexane/EtOAc (95:5 → 80:20).
1
Colorless oil was isolated in 74% yield (0.73 mmol, 223 mg). H NMR (400 MHz, CDCl3) δ
7.59-7.57 (m, 3H), 7.46 (t, J = 7.6 Hz, 2H), 7.30 (d, J = 8.5 Hz, 2H), 7.00 (d, J = 8.5 Hz, 2H),
3.16 (s, 3H), 1.30 (s, 9H). 13C NMR1H (101 MHz, CDCl3) δ 150.5, 138.8, 136.9, 132.6,
128.7, 127.9, 126.2, 125.8, 38.2, 34.6, 31.3. 1H/1H COSY NMR (400 MHz, CDCl3) δH/δH 7.59-
1
7.57/7.46, 7.30/7.00, 3.16/3.16, 1.30/1.30. H/13C HSQC NMR (400 MHz, CDCl3) δH/δC 7.59-
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7.57/127.9, 7.59-7.54/132.6, 7.46/128.7, 7.30/125.5, 7.00/126.2, 3.16/38.2, 1.30/31.3. H/13C
HMBC NMR (400 MHz, CDCl3) δH/δC 7.59-7.57/127.9, 7.59-7.57/132.6, 7.46/128.7,
7.46/136.9, 7.30/125.8, 7.30/138.8, 7.00/126.2, 7.00/138.8, 7.00/150.5, 3.16/138.8, 1.30/31.3,
1.30/34.6, 1.30/150.5. GC/MS EI m/z 304 (M+ +1, 2), 303 (M+, 14), 288 (20), 162 (45), 147
(24), 146 (25), 141 (11), 132 (21), 118 (12), 91 (21), 78 (11), 77 (100), 51 (42). HRMS (ESI-
TOF+) m/z: [M + H]+ Calcd for C17H22NO2S: 304.1366; Found 304.1383.
N-([1,1'-Biphenyl]-2-yl)-N-methylbenzenesulfonamide (1w) was obtained from 1w-s and was
purified by column chromatography on silica gel eluting with pentane/EtOAc (90:10 → 70:30).
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Brown solid was isolated in 80% yield (1.33 mmol, 431.3 mg). H NMR (400 MHz, CDCl3) δ
7.60-7.53(m, 3H), 7.44-7.34 (m, 9H), 7.28-7.23 (m, 1H), 7.01 (d, J = 7.8 Hz, 1H), 2.99 (s, 3H).
13C NMR1H (101 MHz, CDCl3) δ 142.4, 139.3, 139.1, 138.8, 132.5, 131.5, 129.1, 128.8,
128.4, 128.1, 128.1, 127.8, 127.7, 127.2, 39.2. H/1H COSY NMR (400 MHz, CDCl3) δH/δH
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7.60-7.54/7.46-7.35, 7.46-7.35/7.29-7.25, 7.46-7.35/7.00, 7.29-7.25/7.00, 3.00/3.00. 1H/13C
HSQC NMR (400 MHz, CDCl3) δH/δC 7.60-7.54/127.8, 7.60-7.54/132.5, 7.46-7.35/127.2, 7.46-
7.35/128.1, 7.46-7.35/128.4, 7.46-7.35/128.8, 7.46-7.35/129.1, 7.46-7.35/131.5, 7.29-
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7.25/128.1, 7.00/127.7, 3.00/39.2. H/13C HMBC NMR (400 MHz, CDCl3) δH/δC 7.60-
7.54/127.8, 7.60-7.54/132.5, 7.60-7.54/127.8, 7.46-7.35/127.2, 7.45-7.35/127.7, 7.46-
7.35/127.8, 7.46-7.35/128.1, 7.46-7.35/128.8, 7.46-7.35/129.1, 7.46-7.35/138.8, 7.46-
7.35/139.3, 7.46-7.35/142.4, 7.29-7.25/131.5, 7.29-7.25/139.1, 7.00/128.4, 7.00/142.4,
3.00/139.1. GC/MS EI m/z 323 (M+, 1), 182 (66), 181 (26), 180 (28), 167 (85), 166 (14), 152
(15), 115 (11), 77 (100), 51 (54), 50 (11). HRMS (ESI-TOF+) m/z: [M + H]+ Calcd for
C19H18NO2S 324.1053; Found 324.1077.
N-Methyl-N-(4-(trifluoromethoxy)phenyl)benzenesulfonamide (1y) was obtained from 1y-s
and was purified by column chromatography on silica gel eluting with hexane/EtOAc (95:5 →
80:20). Brown oil was isolated in 70% yield (0.7 mmol, 232 mg). 1H NMR (400 MHz, CDCl3) δ
7.61-7.45 (m, 5H), 7.16-7.10 (m, 4H), 3.16 (s, 3H). 13C NMR1H (101 MHz, CDCl3) δ 147.9,
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140.0, 136.2, 133.0, 128.9, 128.0, 127.8, 121.3, 38.1. H/1H COSY NMR (400 MHz, CDCl3)
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7.61-7.45/7.61-7.45, 7.16-7.10/7.16-7.10, 3.16/3.16. H/13C HSQC NMR (400 MHz,
CDCl3) C 7.61-7.45/127.8, 7.61-7.45/128.9, 7.61-7.45/133.0, 7.16-7.10/121.3, 7.16-
1
7.10/128.0, 3.16/38.1. H/13C HMBC NMR (400 MHz, CDCl3) C 7.61-7.45/127.8, 7.61-
7.45/128.9, 7.61-7.45/133.0, 7.61-7.45/136.1, 7.16-7.10/121.3, 7.16-7.10/128.0, 7.16-
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7.10/139.9, 7.16-7.10/147.9, 3.16/139.9. F NMR (377 MHz, CDCl3)  - 58.0. GC/MS EI m/z
332 (M+ +1, 2), 331 (M+, 15), 190 (81), 162 (11), 95 (20), 92 (11), 78 (11), 77 (100), 69 (16), 66
(12), 65 (11), 51 (61), 50 (16). HRMS (ESI-TOF+) m/z: [M + H]+ Calcd for C14H13F3NO3S
332.0563; Found 332.0572.
One-pot Synthesis of N-methyl-N-arylsulfonamides. 1s, 1t, 1x, 1z and 1ab were prepared by
a one-pot synthesis starting from the corresponding anilines (2 mmol). First, the sulfonylation
reaction was carried out according to Methods A to E and secondly, without purification,
methylation reaction proceeded.
N-(4-Fluorophenyl)-N-methylbenzenesulfonamide (1z) was obtained from 4-fluoroaniline
according to Methods E and methylation reaction and was purified by column chromatography
on silica gel eluting with hexane/EtOAc (95:5 → 80:20). Brown oil was isolated in 79% global
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yield (1.57 mmol, 416 mg). H NMR (400 MHz, CDCl3) δ 7.61-7.44 (m, 5H). 7.06-6.95 (m,
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4H), 3.16 (s, 3H). 13C NMR1H (101 MHz, CDCl3) δ 161.5 (d, J = 248 Hz, 1C), 137.4 (d, J =
3, 1C), 136.3, 132.8, 128.8, 128.5 (d, J = 9 Hz, 2C), 127.8, 115.7 (d, J = 23 Hz, 2C), 38.3. 1H/1H
COSY NMR (400 MHz, CDCl3) δH/δH 7.61-7.44/7.61-7.44, 7.06-6.95/7.06-6.95, 3.16/3.16.
1H/13C HSQC NMR (400 MHz, CDCl3) δH/δC 7.61-7.44/127.8, 7.61-7.44/128.8, 7.61-
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7.44/132.8, 7.06-6.95/115.7, 7.06-6.95/128.5, 3.16/38.3. H/13C HMBC NMR (400 MHz,
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CDCl3) δH/δC 7.61-7.44/127.8, 7.61-7.44/128.8, 7.61-7.44/132.8, 7.61-7.44/136.3, 7.06-
6.95/115.7, 7.06-6.95/128.5, 7.06-6.95/137.4, 7.06-6.95/161.5, 3.16/137.4. 19F NMR (377 MHz,
CDCl3) -113.8. GC/MS EI m/z 266 (M+ +1, 2), 265 (M+, 17), 124 (100), 122 (14), 97 (26), 96
(29), 95 (41), 77 (80), 75 (21), 57 (13), 51 (51), 50 (15). HRMS (ESI-TOF+) m/z: [M + H]+
Calcd for C13H13FNO2S 266.0646; Found 266.0654.
N-(3-Acetylphenyl)-N-methylbenzenesulfonamide (1ab) was obtained from 1-(3-amino
phenyl)ethan-1-one according to Methods B and methylation reaction and was purified by
column chromatography on silica gel eluting with hexane/EtOAc (100:0 → 75:25). Orange oil
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was isolated in 65% global yield (1.3 mmol, 373.4 mg). H NMR (400 MHz, CDCl3) δ 7.87-
13
7.85 (m, 1H), 7.62-7.37 (m, 8H), 3.20 (s, 3H), 2.56 (s, 3H). C NMR 1H (101 MHz, CDCl3)
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δ 197.1, 142.0, 137.7, 136.0, 133.0, 131.4, 129.1, 128.8, 127.7, 127.1, 125.7, 37.9, 26.6. H/1H
COSY NMR (400 MHz, CDCl3) δH/δH 7.87-7.85 /7.62-7.37, 3.20/3.20, 2.56/2.56. 1H/13C HSQC
NMR (400 MHz, CDCl3) δH/δC 7.87-7.85 /121.1, 7.62-7.37/125.7, 7.62-7.37/133.0, 7.62-
7.37/127.7, 7.62-7.37/129.1, 7.62-7.37/128.8, 7.62-7.37/131.4. 1H/13C HMBC NMR (400 MHz,
CDCl3) δH/δC 7.87-7.85 /125.7, 7.87-7.85 /134.4, 7.87-7.85/197.1, 7.62-7.37/127.1, 7.62-
7.37/127.7, 7.62-7.37/128.8, 7.62-7.37/131.4, 7.62-7.37/133.0, 7.62-7.37/136.0, 7.62-
7.37/137.7, 7.62-7.37/142.0, 7.62-7.37/197.1, 3.20/142.0, 2.56/197.1. HRMS (ESI-TOF+) m/z:
[M + H]+ Calcd for C15H16NO3S 290.0845; Found 290.0860.
Desulfonylation Reactions in Dark Conditions. The desulfonylation reaction was carried out
in a Schlenk tube equipped with an inert N2 inlet and magnetic stirred at rt. In the Schlenk tube,
DMSO (1 mL) was dried and deoxygenated, then the corresponding sulfonamide (1 equiv, 0.1
mmol) and KOtBu (3 equiv, 0.3 mmol) were added and the mixture was protected from light
with aluminum foil. After the reaction was finished, it was quenched with NH4NO3 or NH4Cl
and water in excess and the residue was extracted with EtOAc (3 x 30 mL), the organic layers
extracted were combined, washed with water, dried with anhydrous Na2SO4 and concentered
under reduced pressure to leave the crude products. Yields were quantified by GC employing
internal method using biphenyl as internal standard.
Photodesulfonylation Reactions under Visible Light Irradiation. The photodesulfonylation
reactions were carried out in a vial at rt and under N2 atmosphere and irradiated with blue- LED
(3 W) using 1 equiv. (0.1 mmol) of sulfonamide, 2.2 equiv. of KOtBu (0.22 mmol) and 2 equiv.
of Hantzsch ester (0.2 mmol) in DMSO (1 mL previously dried and deoxygenated). After the
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reaction was finished, it was quenched with NH4NO3 or NH4Cl and water in excess and the
residue was extracted with EtOAc (3 x 30 mL), the organic layers extracted were combined,
washed with water, dried with anhydrous Na2SO4 and concentered under reduced pressure to
leave the crude products. Yields were quantified by GC using internal method employing 9H-
carbazole as internal standard.
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Characterization Data of Desulfonylation Products (2). 1H-Indole (2a), 1H-pyrrolo[2,3-
b]pyridine (2b), 1H-benzo[d][1,2,3]triazole (2c), 1H-pyrrole (2d), 9H-carbazole (2e),
diphenylamine (2i), aniline (2k), 4-methoxyphenol (2n), 4-hydroxybenzonitrile (2o), 2-
iodophenol (2p) and 1-benzyl-1H-indole (2q) were identified by comparing with authentic
samples (GC/FID and GC–MS).
1H-Indole (2a). Titled compound was purified by column chromatography on silica gel eluting
with hexane/EtOAc (100:0 → 80:20) in 91% yield (0.091 mmol, 10.6 mg) as white solid.
Starting from 0.5 mmol of substrate, 88% isolated yield (0.44 mmol, 51.5 mg) was obtained.
For large-scale reaction, 86% isolated yield (3.6 mmol, 423 mg) starting from 1.080 g of
substrate.
1H-pyrrolo[2,3-b]pyridine (2b). Titled compound was purified by column chromatography on
silica gel eluting with hexane/EtOAc (100:0 → 80:20) in 87% yield (0.087 mmol, 10.2 mg) as
white solid.
1H-benzo[d][1,2,3]triazole (2c). Titled compound was purified by column chromatography on
silica gel eluting with hexane/EtOAc (100:0 → 80:20) in 67% yield (0.067 mmol, 8.0 mg) as
white solid.
1H-pyrrole (2d). Titled compound was purified by column chromatography on silica gel
eluting with hexane/EtOAc (100:0 → 80:20) in 99% yield (0.099 mmol, 6.6 mg) as colorless
oil.
9H-carbazole (2e). Titled compound was purified by column chromatography on silica gel
eluting with hexane/EtOAc (100:0 → 80:20) in 47% yield (0.047 mmol, 7.8 mg) as white solid.
Diphenylamine (2i). Titled compound was obtained in 72% yield (0.072 mmol, 12.2 mg) as
brown solid.
4-Methoxyphenol (2n). Titled compound was purified by column chromatography on silica gel
eluting with hexane/EtOAc (50:50) in 75% yield (0.075 mmol, 9.3 mg) as light-pink solid.
4-Hydroxybenzonitrile (2o). Titled compound was purified by column chromatography on
silica gel eluting with hexane/EtOAc (50:50) in 90% yield (0.09 mmol, 10.7 mg) as white solid.
2-Iodophenol (2p). Titled compound was purified by column chromatography on silica gel
eluting with hexane/EtOAc (50:50) in 93% yield (0.093 mmol, 20.5 mg) as grey solid.
1-Benzyl-1H-indole (2q). Titled compound was purified by column chromatography on silica
gel eluting with hexane/EtOAc (80:20) in 98% yield (0.098 mmol, 20.3 mg) as colorless oil.
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N-Methylaniline (2l).134 Titled compound was purified by column chromatography on silica gel
eluting with hexane/EtOAc (90:10 → 50:50) in 95% yield (0.095 mmol, 10 mg) as brown oil.
1H NMR (400 MHz, CDCl3) δ 7.20-7.16 (m, 2H), 6.70 (t, J = 7.3 Hz, 1H), 6.59 (d, J = 7.7 Hz,
2H), 3.64 (s br, 1H), 2.80 (s, 3H). 13C NMR1H (101 MHz, CDCl3) δ 149.3, 129.1, 117.2,
112.3, 30.6. GC/MS EI m/z 108 (8, M+ +1), 107 (81 M+), 106 (100), 79 (33), 78 (14), 77 (39),
65 (14), 51 (23), 50 (8).
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N-(4-Hydroxyphenyl)-N,4-dimethylbenzenesulfonamide (2m).135 Titled compound was
purified by column chromatography on silica gel eluting with hexane/EtOAc (90:10 → 50:50).
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Brown oil was isolated in 44 % yield (0.014 mmol, 4 mg). H NMR (400 MHz, CDCl3) δ 7.45
(d, J = 8.0 Hz, 2H), 7.26-7.24 (m, 2H), 6.93 (d, J = 8.6 Hz, 2H), 6.73 (d, J = 8.6 Hz, 2H), 5.19 (s
br, 1H), 3.12 (s, 3H), 2.42 (s, 3H). 13C NMR1H (101 MHz, CDCl3) δ 154.9, 143.5, 134.4,
133.6, 129.3, 128.4, 128.0, 115.6, 38.4, 21.5. GC/MS EI m/z 279 (M+ +2, 1), 278 (M+ +1, 2),
277 (M+, 10), 123 (7), 122 (100), 94 (19), 91 (11), 65 (18).
4-Methoxy-N-methylaniline (2s).136 Titled compound was purified by column chromatography
on silica gel eluting with hexane/EtOAc (100:0 → 70:30). Light yellow oil was isolated in 80 %
yield (0.08 mmol, 9.8 mg). 1H NMR (400 MHz, CDCl3) δ 7.25 (s, 1H), 6.82-6.78 (m, 2H), 6.61-
6.57 (m, 2H), 3.75 (s, 3H), 2.80 (s, 3H). 13C NMR1H (101 MHz, CDCl3) δ 152.1, 143.7,
114.9, 113.6, 55.8, 31.6. GC/MS EI m/z 138 (M+ +1, 4), 137 (M+, 61), 122 (100), 94 (60), 77
(13), 67 (13), 66 (12), 65 (35), 63 (23), 53 (18), 52 (26), 51 (15), 50 (8).
4-Methyl-N-methylaniline (2t).134 Titled compound was obtained in 98% yield (0.098 mmol,
11.9 mg). 1H NMR (400 MHz, CDCl3) δ 6.99 (d, J = 8.5 Hz, 2H), 6.54 (d, J = 8.4 Hz, 2H), 3.51
13
(s br, 1H), 2.80 (s, 3H), 2.24 (s, 3H). C NMR1H (101 MHz, CDCl3) δ 147.2, 129.7, 126.4,
112.6, 31.1, 20.3. GC/MS EI m/z 122 (M+ +1, 7), 121 (M+, 93), 120 (100), 106 (13), 91 (41), 89
(10), 79 (12), 78 (15), 77 (26), 65 (25), 63 (16), 60 (12), 53 (11), 52 (18), 51 (26), 50 (16).
4-Cyano-N-methylaniline (2u).137 Titled compound was purified by column chromatography
on silica gel eluting with hexane/EtOAc (80:20 → 50:50) as colorless oil and isolated in 50 %
yield (0.05 mmol, 6.6 mg). 1H NMR (400 MHz, CDCl3) δ 7.43 (d, J = 8.6 Hz, 2H), 6.55 (d, J =
8.6 Hz, 2H), 4.25 (s br, 1H), 2.88 (s, 3H). 13C NMR1H (101 MHz, CDCl3) δ 152.2, 133.7,
120.4, 111.8, 30.0. GC/MS EI m/z 133 (M+ +1, 7), 132 (M+, 74), 131 (100), 104 (22), 102 (14),
77 (17), 76 (13), 75 (14), 66 (12), 64 (11), 63 (13), 51 (15), 50 (11).
4-(tert-Butyl)-N-methylaniline (2v).136 Titled compound was purified by column
chromatography on silica gel eluting with hexane/EtOAc (95:5 → 80:20) as colorless oil and
isolated in 80 % yield (0.08 mmol, 13.0 mg). 1H NMR (400 MHz, CDCl3) δ 7.22 (d, J = 8.5 Hz,
2H), 6.59 (d, J = 8.5 Hz, 2H), 3.57 (s br, 1H), 2.82 (s, 3H), 1.28 (s, 9H). 13C NMR1H (101
MHz, CDCl3) δ 147.0, 140.1, 126.0, 112.2, 33.8, 31.6, 31.0. GC/MS EI m/z 164 (M+ +1, 3), 163
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(M+, 28), 149 (11), 148 (100), 133 (16), 120 (21), 108 (12), 107 (13), 91 (13), 77 (16), 65 (12),
50 (3).
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N-Methyl-[1,1'-biphenyl]-2-amine (2w).134 Titled compound was purified by column
chromatography on silica gel eluting with hexane/EtOAc (100:0 → 90:10) as light yellow oil
and isolated in 86 % yield (0.086 mmol, 15.7 mg). 1H NMR (400 MHz, CDCl3) δ 7.44-7.40 (m,
4H), 7.35-7.32 (m, 2H), 7.08 (dd, J =7.4, 1.2 Hz, 1H), 6.76 (t, J = 7.4 Hz, 1H), 6.68 (d, J = 8.1
Hz, 1H), 4.09 (s br, 1H), 2.78 (s, 3H).
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4-(Trifluoromethoxy)-N-methylaniline (2y).137 Titled compound was purified by column
chromatography on silica gel eluting with hexane/EtOAc (90:10 → 70:30) as a colorless oil and
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isolated in 58 % yield (0.058 mmol, 11.1 mg). H NMR (400 MHz, CDCl3) δ 7.03 (d, J = 8.8
Hz, 2H), 6.54-6.52 (m, 2H), 3.72 (s br, 1H), 2.8 (s, 3H). 13C NMR1H (101 MHz, CDCl3) δ
148.1, 140.4, 122.3, 120.8 (q, J = 255 Hz, 1C), 112.5, 30.7. GC/MS EI m/z 192 (M+ +1, 6), 191
(M+,60), 190 (16), 123 (10), 122 (100), 106 (11), 95 (16), 94 (54), 79 (12), 78 (12), 77 (32), 75
(11), 69 (36), 67 (15), 66 (15), 65 (38), 64 (16), 63 (21), 53 (17), 52 (23), 51 (14).
4-Fluoro-N-methylaniline (2z).137 Titled compound was obtained in 85% yield (0.085 mmol,
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10.6 mg) as a colorless oil. H NMR (400 MHz, CDCl3) δ 6.93-6.86 (m, 2H), 6.55-6.51 (m,
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2H), 3.32 (s br, 1H), 2.80 (s, 3H). C NMR1H (101 MHz, CDCl3) δ 155.8 (d, J = 234, 1C),
145.7, 115.6 (d, J = 22 Hz, 2C), 113.1 (d, J = 7 Hz, 2C), 31.3. GC/MS EI m/z 126 (M+ +1, 7),
125 (M+, 89), 124 (100), 97 (32), 96 (20), 95 (20), 83 (23), 77 (17), 75 (18), 62 (15), 57 (12).
1-(3-(Methylamino)phenyl)ethan-1-one (2ab).138 Titled coumpound was purified by column
chromatography on silica gel eluting with hexane/EtOAc (90:10 → 70:30) as a white solid in
85% yield (0.085 mmol, 12.7 mg) as a white solid. 1H NMR (400 MHz, CDCl3) δ 7.28-7.26 (m,
2H), 7.20-7.18 (m, 1H), 6-81-6.78 (m, 1H), 3.90 (s br, 1H), 2.88 (s, 3H), 2.58 (s, 3H).
Photoinduced Reduction of Aryl Halides in presence of HE. The photostimulated reduction
was carried out under N2 atmosphere using 1 equiv. (0.1 mmol) of the corresponding aryl
halide, 2 equiv. of HE and KOtBu (2.2 equiv) in DMSO (1 mL) and irradiating with 3 W blue
LED at rt. DMSO was previously dried and deoxygenated. After the reaction was finished, it
was quenched with NH4NO3 or NH4Cl and water in excess. The residue was extracted with
EtOAc (3 x 30 mL), and the organic layers were combined, washed with water, dried with
anhydrous Na2SO4 and concentered under reduced pressure to leave the crude products. Yields
were quantified by GC using internal method using 9H-carbazole as internal standard.
Naphtalene (11a), anthracene (11d), phenanthrene (11e), biphenyl (11f), pyridine (11g) and
cyanobenzene (11i) were identified by comparing with authentic samples (GC/FID and GC–
MS).
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Naphtalene (11a). Titled compound was obtained in 81% yield (0.081 mmol, 10.4 mg) as a
white solid.
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Anthracene (11d). Titled compound was obtained in 89 % yield (0.089 mmol, 15.9 mg) as a
white solid.
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Phenanthrene (11e). Titled compound was obtained in 93 % yield (0.093 mmol, 16.5 mg) as
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white solid.
Biphenyl (11f). Titled compound was obtained in 76 % yield (0.076 mmol, 11.6 mg) as a white
solid.
Pyridine (11g). Titled compound was obtained in 59 % yield (0.059 mmol, 4.67 mg) as a
colorless oil.
Cyanobenzene (11i). Titled compound was obtained in 45 % yield (0.045 mmol, 4.6 mg) as a
colorless oil.
ASSOCIATED CONTENT
Supporting Information
The Supporting Information is available free of charge on the ACS Publications website. Extra
experimental details, UV−vis spectra, H NMR and 13C NMR1H spectra for substrates and
1
products, Emission Spectrum for Blue-LEDs and HPIT 400W lamps (≥ 350 nm, Figures S1
and S2), Figures S3-S6, and Tables S1−S3 (PDF).
AUTHOR INFORMATION
Corresponding Author
*E-mail for M. E.B.: eugebuden@unc.edu.ar
ORCID:
Micaela D. Heredia: 0000-0002-5688-4162
Walter D. Guerra: 0000-0003-0712-2740
Silvia M. Barolo: 0000-0003-3730-0018
Santiago J. Formasier: 0000-0001-8675-1160
Roberto A. Rossi: 0000-0001-8659-082X
María E. Budén: 0000-0002-2424-3299
Notes
The authors declare no competing financial interest.
ACKNOWLEDGEMENTS
This work was supported partly by Agencia Cꢀrdoba Ciencia, Consejo Nacional de
Investigaciones Científicas y Técnicas (CONICET), Secretaría de Ciencia y Tecnología,
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Universidad Nacional de Cꢀrdoba (SECyT) and Agencia Nacional de Promoción Científica y
Técnica (ANPCyT). M. D. H. gratefully acknowledge receipt of fellowship from CONICET.
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REFERENCES AND ENDNOTES
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(1)
Wuts, P. G. M.; Greene, T. W. Protection for the Amino Group. In Greene’s Protective
Groups in Organic Synthesis; John Wiley & Sons, Inc.: Hoboken, NJ, USA, 2006; 696–
926.
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(2)
(3)
(4)
(5)
(6)
(7)
(8)
(9)
Thomas, E. J. Protecting Groups. Philip J. Kocienski. Georg Thieme, Stuttgart, New
York. Appl. Organomet. Chem. 2001, 15, 725-726.
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