Protocol for Visible-Light-Promoted Desulfonylation Reactions Utilizing Catalytic Benzimidazolium Aryloxide Betaines and Stoichiometric Hydride Donor Reagents

Article abstract of DOI:10.1021/acs.joc.0c00038

An unprecedented photocatalytic system consisting of benzimidazolium aryloxide betaines (BI⁺-ArO^-) and stoichiometric hydride reducing reagents was developed for carrying out desulfonylation reactions of N-sulfonyl-indoles,-amides, and-amines, and α-sulfonyl ketones. Measurements of absorption spectra and cyclic voltammograms as well as density functional theory (DFT) calculations were carried out to gain mechanistic information. In the catalytic system, visible-light-activated benzimidazoline aryloxides (BIH-ArO^-), generated in situ by hydride reduction of the corresponding betaines BI⁺-ArO^-, donate both an electron and a hydrogen atom to the substrates. A modified protocol was also developed so that a catalytic quantity of more easily prepared hydroxyaryl benzimidazolines (BIH-ArOH) is used along with a stoichiometric hydride donor to promote the photochemical desulfonylation reactions.

Full text of DOI:10.1021/acs.joc.0c00038

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Article
A protocol for visible light promoted desulfonylation
reactions utilizing catalytic benzimidazolium aryloxide
betaines and stoichiometric hydride donor reagents
Eietsu Hasegawa, Tsukasa Tanaka, Norihiro Izumiya, Takehiro Kiuchi,
Yuuki Ooe, Hajime Iwamoto, Shin-ya Takizawa, and Shigeru Murata
J. Org. Chem., Just Accepted Manuscript • DOI: 10.1021/acs.joc.0c00038 • Publication Date (Web): 19 Feb 2020
Downloaded from pubs.acs.org on February 20, 2020
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A protocol for visible light promoted desulfonylation reactions utilizing catalytic
benzimidazolium aryloxide betaines and stoichiometric hydride donor reagents
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Eietsu Hasegawa,†* Tsukasa Tanaka,† Norihiro Izumiya,† Takehiro Kiuchi,† Yuuki Ooe,†
Hajime Iwamoto,† Shin-ya Takizawa,‡ Shigeru Murata‡
†Department of Chemistry, Faculty of Science, Niigata University, 8050 Ikarashi-2, Nishi-ku,
Niigata 950-2181, Japan.
‡Department of Basic Science, Graduate School of Arts and Sciences, The University of Tokyo,
3-8-1 Komaba, Meguro-ku, Tokyo, 153-8902, Japan
Visible light absorbing
electron & hydrogen donor photo-catalyst
h

hydride donor
Me
Me
N
H–
N
+
R– H
H
O–
N
N
Me
O–
Desulfonylation
Me
Me
NaBH4
N BH3
R– SO2R’
ABSTRACT: An unprecedented photocatalytic system consisting of benzimidazolium aryloxide
betaines (BI+–ArO–) and stoichiometric hydride reducing reagents was developed for carrying out
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desulfonylation reactions of N-sulfonyl-indoles, -amides and -amines, and -sulfonylketones.
Measurements of absorption spectra and cyclic voltammograms as well as DFT calculations were
carried out to gain mechanistic information. In the catalytic system, visible light activated
benzimidazoline aryloxides (BIH–ArO–), generated in-situ by hydride reduction of the
corresponding betaines BI+–ArO–, donate both an electron and a hydrogen atom to the substrates. A
modified protocol was also developed so that a catalytic quantity of more easily prepared
hydroxyaryl benzimidazolines (BIH–ArOH) is used along with a stoichiometric hydride donor to
promote the photochemical desulfonylation reactions.
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INTRODUCTION
Photoinduced electron transfer (PET) is a fundamental photochemical process involving single
electron transfer (SET) promoted reduction and oxidation (redox) of excited states of substances.
Extensive investigations of PET reactions conducted during the past several decades have led to the
discovery of variety of unique organic redox reactions.1 About a decade ago, the synthetic potential
of PET reactions, promoted by visible light-absorbing transition metal photoredox catalysts, were
anew demonstrated in independent studies by MacMillan, Yoon and Stephenson.2 Since then,
numerous synthetically useful photoredox reactions catalyzed by these metal complexes have been
reported.3 In contrast, protocols to accomplish visible light promoted redox reactions without using
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expensive and potentially toxic transition metal catalysts have been less well-developed. In
particular, processes promoted by organic photoredox catalysts are more desirable from a green and
sustainable perspective.
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Although a variety of organic electron-acceptor photocatalysts have been developed, their
electron-donor counterparts have been less well-explored.4 As a matter of fact, organic
photocatalysts of this type are limited to electron-donating substituent possessing arenes,
heteroarenes and dyes.5 Only recently other electron-donor photocatalysts and new protocols for
carrying out visible light induced reduction reactions have been described (Figure 1).6 The most
general types of electron donor photocatalysts (D-PC) investigated to date possess excited states
that act as SET donors (reductants) (Type A). In Type A catalytic cycles, the radical cation (D-PC•+)
generated by SET from the D-PC is converted back to D-PC by SET from an appropriate electron
donor quencher Q.5,6c,6f,6k,6l,6n Another protocol (Type B) for carrying out light induced reduction
reactions involves quenching of an excited state of an electron acceptor (A-PC) by SET from Q to
generate radical anion A–PC•–, which serves as a reductant.6a,6e,6g,6h,6m In yet another version (Type
C), a strongly reducing excited state of a preformed A–PC•– serves as the reductant.6b,6d,6i,6j
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h
h
(Type A)
D-PC
(Type B)
A-PC
(Type C)
h
*
[(A-PC)•– ]*
A-PC•–
*
D-PC
A-PC
R
•–
•+
R
R
Q
Q
9
•+
D-PC
•–
A-PC
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•–
•+
R
Q
•–
Q
R
R
A-PC
PC: photocatalyst, D-PC: electron donor PC, A-PC: electron acceptor PC
Q: quenchers (electron donors)
R: reactants (electron acceptors)
Figure 1. Three types of pathways for electron-donor photocatalyzed reduction reactions.
2-Aryl-1,3-dimethylbenzimidazolines (BIH–Ar), artificial analogues of the reduced form
(NADH) of nicotinamide adenine dinucleotide, serve as effective hydride, hydrogen atom and
electron donors.7 In earlier studies aimed at developing new organic transformations, we have
shown that BIH–Ar can be utilized as organic reductants in unique photoreduction reactions.8
Moreover, we demonstrated that introduction of hydroxyl substituents on the 2-aryl rings of BIH–
Ar gives substances (BIH–ArOH) which are deprotonated to form aryloxide analogs BIH–ArO– that
are exceptionally strong electron donors.9 For example, the electronic excited states of
2-hydroxynaphthyl-1,3-dimethylbenzimidazoline (BIH–NapOH) in the presence and absence of
appropriate bases promote reductive transformations of various organic substances (Figure 2),
which generate benzimidazolium naphthoxide (BI+–NapO–) as a stoichiometric co-product.
Recently, we discovered that BI+–NapO– is unprecedented visible light absorbing betaine
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photocatalyst,6k and that the excited state of BIH–NapO– is a stronger SET-donor than that of BI+–
NapO–.9d Also, we found that BI+–Ar, formed in the photoreduction reactions promoted by
stoichiometric quantities of BIH–Ar, can be isolated and reduced to reform BIH–Ar using hydride
donors.9a
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Figure 2. A hydroxynaphthyl-benzimidazoline (BIH–NapOH) and benzimidazolium naphthoxide
(BI+–NapO–) redox process in the operation of stoichiometric and catalytic photoreduction
reactions.
In the investigation described below, we utilized knowledge gained from our earlier efforts to
design a new protocol for visible light promoted photocatalyzed reduction reactions. In the
proposed process, BIH–ArO– serving as a photocatalyst is regenerated in-situ by reduction of BI+–
ArO– with stoichiometric amounts of simple hydride donor reagents (Figure 2).10,11 Moreover, in
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addition to being electron donors in these reactions like ordinary photocatalysts,5,6 BIH–ArO–
would donate hydrogen atoms to the substrates.12 To assess this unique design of a photocatalytic
system, we utilized five benzimidazolium aryloxides (BI+–ArO–, 1, Figure 3) as photocatalysts
together with NaBH4, picoline borane (Pic-BH3) and pinacol borane (Pin-BH) as hydride donor
reagents (Figure 3). Furthermore, because stoichiometric quantities of the reduced form of 1a
(BIH–NapOH, Figure 2) were previously observed to promote reductive desulfonylation
reactions,9d,13 we chose N-sulfonyl-indoles, -amide and -amines, and -sulfonylketones as probe
substrates to evaluate the new photocatalytic system (Figure 4).
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Figure 3. Hydride addition reactions of benzimidazolium aryloxides 1.
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Figure 4. Photocatalyzed desulfonylation reactions of N-sulfonyl-indoles 2, -amide 4 and -amines 6
and 8, and -sulfonylketones 10.
RESULTS AND DISCUSSION
In the first phase of this investigation, we carried out absorption spectroscopic measurements of
BI+–ArO– (1) in the absence and presence of hydride reducing agents (Figure S1, Table S1 and
Figure S2). We found that the spectrum of BI+–NapO– (1a) in DMSO contains a long wavelength
maximum at 415 nm6k which disappears upon addition of NaBH4 (Figure 5, also see Figure S3 for
1b, Figure S4 for 1c and Figure S5 for 1d). Subsequent addition of t-BuOK results in the
appearance of a spectrum with an absorption maximum at 399 nm. Importantly, the former and the
latter absorption spectra are similar to those of BIH–NapOH (1a-HH) and BIH–NapO– (1a-H, max
= 402 nm), respectively.9d These observations demonstrate that BI+–NapO– is reduced by hydride
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transfer from NaBH4 to form 1a-H, which exists in a base controlled equilibrium with 1a-HH.
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Figure 5. Absorption spectra of BI+–NapO– (1a) and BIH–NapOH (1a-HH) in the absence and
presence of NaBH4 (12.0 equiv) and t-BuOK (12.0 equiv) in DMSO (4.0 x 10-5 M). BIH–NapO–
(1a-H) was generated from 1a-HH by the addition of t-BuOK. Proposed structures of 1a, 1a-H and
1a-HH are also shown.
To assess the feasibility of the proposed photocatalytic process, visible light irradiation
induced desulfonylation reactions of N-sulfonylindoles 2a–2c were explored. The electron
accepting abilities of these substances are estimated by utilizing their respective Ered1/2 values (V vs
SCE) of -1.67 for 2a, -1.74 for 2b and -1.92 for 2c.9d The general procedure used in the
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photoreactions involves Xe lamp or white light emitting diode (LED) irradiation of nitrogen purged
DMSO solutions containing 2a–2c, BI+–ArO– catalysts 1a–1e (10 mol%) and various hydride
donors. The results summarized in Table 1 show that Xe-lamp irradiation of a solution of 1a,
tosylate 2a and a greater than stoichiometric quantity of NaBH4 leads to complete consumption of
2a and high yielding formation of the desulfonylation product 3a (entry 1). In contrast, incomplete
conversion along with lower yield product formation takes place when less than a stoichiometric
quantity of NaBH4 is employed (entry 2). The results of additional exploratory experiments show
that both 1a and NaBH4 are necessary to promote the desulfonylation reaction (entries 3 and 4), and
that the reaction proceeds smoothly in other polar solvents such as DMF, MeCN, MeOH and THF
but not in less polar CH2Cl2 and PhCH3 (compare entry 1 with Table S2). Moreover, other hydride
donor reagents such as NaCNBH3, PinBH and PicBH3 are also usable but the processes promoted
by these substances are less efficient (entries 5, 6 and 7). Although longer times are required,
irradiation using the LED source promotes the desulfonylation reaction (entries 8 and 10). The
presence of t-BuOK leads to a noticeable enhancement of the reaction progress but a slightly
decreased mass balance occurs (compare entry 9 with entry 8). Although longer reaction times are
required for methanesulfonate 2b and weaker electron accepting 2c, photocatalyzed desulfonylation
reactions of these sulfonates take place smoothly to form the respective products 3b and 3c (entries
11, 12 and 13). Finally, phenoxide containing betaines 1b, 1c, 1d and 1e also serve as
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photocatalysts, and NaBH4 and Me4NBH4 as hydride reductants (entries 14-19) for the
desulfonylation reaction of 2a with catalytic activities reflected in conversion vs time ratios in the
order of 1a > 1b > 1d > 1c > 1e (entries 1, 14, 17, 18 and 19).
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Table 1. Photoreductive desulfonylation reactions of N-sulfonylindoles 2 promoted by betaine
photocatalysts BI+–ArO– (1) and hydride donorsa
hydride
donor
light
source
Xe
irradiation
conv of 2
(%)b
100
80
yield of 3
(%)b,c
92
entry
1
2
time (h)
1
1a
1a
2a
2a
2a
2a
2a
2a
2a
2a
2a
2a
2b
2b
2c
2a
2a
2a
2a
NaBH4
1
1
1
1
1
1
1
1
1
5
2
5
3
1
1
12
1
d
2
NaBH4
NaBH4
Xe
72 (90)
0
e
3
-
Xe
3
f
4
1a
1a
1a
1a
1a
1a
1a
1a
1a
1a
1b
1b
1b
1c
-
Xe
7
6 (86)
20 (50)
59 (81)
40 (91)
29 (97)
51 (85)
94 [90]g
95
5
NaCNBH3
PinBH
Xe
40
6
Xe
73
7
PicBH3
NaBH4
NaBH4
NaBH4
NaBH4
NaBH4
NaBH4
NaBH4
Me4NBH4
NaBH4
NaBH4
Xe
44
8
LED
LED
LED
Xe
30
9h
10
11
12
13
14
15
16
17
60
100
100
100
100
66
LED
Xe
91
90
Xe
53 (80)
35 (95)
90
Xe
37
LED
Xe
100
38
27 (71)
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1d
1e
2a
2a
NaBH4
NaBH4
Xe
Xe
1
1
51
25
39 (76)
24 (96)
a2 (0.10 mmol), 1 (10 mol%), hydride donor (1.2 equiv): 2-picoline borane (PicBH3), pinacol
borane (PinBH), DMSO (1.0 mL); 500 W Xe-lamp ( > 390 nm) or 7.3 W LED. bDetermined by
using 1H NMR. cYields in the parenthesis are based on conversions. dNaBH4 (0.5 equiv). eAbsence
of 1a. fAbsence of hydride donor. gIsolated by using column chromatography. ht-BuOK (0.5 equiv)
is present.
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To explore the scope of the developed photocatalytic protocol, desulfonylation reactions of the
N-sulfonyl-amide 4, -amines 6 and 8, and -sulfonylketones 10a and 10b were examined (Table 2
and Table S3). Their Ered1/2 values (V vs SCE) were reported to be -1.58 for 4,9d -2.07 for 6,9d -2,39
V for 8,9d -1.48 for 10a,6k and –1.89 for 10b6k. Xe and LED irradiations of nitrogen purged DMSO
solutions of N-sulfonylbenzamide 4 using 1a and 1b as photocatalysts, and NaBH4 as the hydride
reductant promote reactions to form the corresponding amide 5 (entries 1, 2 and 8).14 Notably, a
lower quantity of 1a (1 mol%) can be employed to promote complete conversion of 4 although a
longer irradiation time is required and the yield of 5 is lower (entry 3). As expected, the reaction is
significantly deterred in the absence of either 1a, a hydride donor or irradiation (entries 4–6). The
order of catalytic activity of the betaines (1a > 1b > 1d > 1c) for this process is similar to that for
the reaction of 2a (entries 2, 7, 9-10 and Table 1). Photocatalyzed detosylation reactions of
N-tosylamine 6 and 8 also occur under the same conditions and using longer Xe and LED
irradiation times to produce the respective amines 7 and 9 in excellent yields (entries 11-13, also see
Table S3).15 Since ketone carbonyls are reduced by using NaBH4, PicBH3 was utilized as the
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hydride reducing agent in photocatalyzed desulfonylation reactions of -sulfonylketones 10a and
10b. Both betaines 1a and 1b serve to promote Xe or LED irradiation induced reactions of 10a to
produce 11a in high yields (entries 14, 15 and 17, also see Table S3) while shorter time irradiation
(2.5 h) by LED did not complete the reaction using 1a as a catalyst (entry 16). In contrast, light
source and irradiation time employed to induce efficient reaction of 8 (entry 13) are not effective to
cause desulfonylation of 10b (entry 18). The results of experiments aimed at determining the effect
of base on the latter desulfonylation reactions show that, while K2CO3 significantly accelerates the
formation of 11b (entry 19), use of the more DMSO soluble base Cs2CO3 results in a higher
yielding process (entry 20).
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Table 2. Photoreductive desulfonylation reactions of of N-sulfonyl-amide 4, -amines 6, 8, and
-sulfonylketones 10a-b promoted by betaine photocatalysts BI+–ArO– (1) and hydride
donorsa
hydride
donor
light
irradiation conv of
yields of
5,7,9,11 (%)b,c
98
entry
1
substrate
source
Xe
time (h)
4,6,8,10 (%)b
1
2
3
1a
1a
1ae
4
4
4
NaBH4
NaBH4
NaBH4
0.5
1
100
100
100
LED-1
LED-1
96 [86]d
2
80
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f
4
-
4
NaBH4
LED-1 24
5
0
g
5
1a
1a
1b
1b
1c
1d
1a
1a
1a
1a
1a
1a
1b
1a
1a
1a
4
-
LED-1
1
3
Trace
Trace
27 (64)
74
h
6
4
NaBH4
NaBH4
NaBH4
NaBH4
NaBH4
NaBH4
NaBH4
NaBH4
PicBH3
PicBH3
PicBH3
PicBH3
PicBH3
PicBH3
PicBH3
-
1
6
7
4
LED-1
LED-1
LED-1
LED-1
Xe
1
42
8
4
3
100
7
10
11
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13
14
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9
4
1
Trace
18 (78)
96
10
11
12
13
14
15
16
17
18
19i
20k
4
1
23
6
18
100
100
100
100
100
72
6
LED-1 24
LED-2 48
96 [92]d
8
87
10a
10a
10a
10a
10b
10b
10b
Xe
5
94
LED-1 24
LED-1 2.5
LED-1 24
LED-2 48
LED-2 48
LED-2 48
91 [91]d
62 (86)
85
100
26
22 (85)
74
~100j
100
85
aSubstrate (0.10 mmol), 1 (10 mol%), hydride donor (1.2 equiv): 2-picoline borane (PicBH3),
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solvent (1.0 mL); 500 W Xe-lamp ( > 390 nm), 7.3 W LED (LED-1) or 10.8 W LED x 2 (LED-2).
1
c
d
bDetermined by using H NMR. Yields in the parenthesis are based on conversion. Isolated by
e
f
g
h
using column chromatography. 1a (1 mol%) was used. Absence of 1a. Absence of NaBH4. No
i
j
1
irradiation is performed. K2CO3 (1.0 equiv) is present. Trace of 10b was detected by using H
NMR. kCs2CO3 (1.0 equiv) is present.
Reduced aryloxide betaines BIH–ArO– (1-H) are the expected intermediates in the mechanistic
cycle for the photocatalyzed desulfonylation reactions described above. Oxidation potential
measurements and DFT calculations16 were carried out in order to examine the electron donor
properties of these intermediates and the corresponding protonated forms BIH–ArOH (1-HH). The
results show that 1-HH have Eox values in the range of = +0.31 to +0.37 V (vs SCE) which is
1/2
consistent with the finding that the highest occupied molecular orbitals (HOMOs) are highly
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localized on the benzimidazoline moiety regardless of the nature of the aryloxy substituent (Figure
S7-S8 and Table S4). In contrast, the magnitudes of the HOMO coefficients are greater at positions
in the aryloxide moieties of 1-H (Figure 6). This result is consistent with the observation that the
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oxidation potentials of these intermediates are significantly lower (Eox = +0.06 to +0.19V) than
1/2
those of 1-HH and the expectation that electron donation is enhanced by the presence of the
aryloxide moieties.6k,9d,17 As previously discussed,9c,9d photoexcitation of BIH–NapO– (1a-H)
produces a naphthoxide like excited state. Indeed, the lowest unoccupied molecular orbital (LUMO)
of 1a-H is located on the naphthoxide moiety (Figure 6). On the other hand, LUMOs of phenoxide
possessing reduced betaines 1b-H–1e-H are located on the benzimidazoline moieties (Figure 6),
and thus, electronic excited states of these intermediates might have charge-transfer characters.
Figure 6. Frontier orbital coefficients of BIH–ArO– (1–H) obtained by using DFT calculations
(6-31+G(d)).
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The mechanism depicted in Scheme 1 for the photocatalyzed desulfonylation reactions is fully
consistent with the results and information presented above. In the pathway, hydride reduction of
BI+–ArO– (1) produces BIH–ArO– (1-H), which exist in an acid-base equilibrium with BIH–ArOH
(1-HH) that favors the deprotonated form in the presence of an appropriate base such as t-BuOK
(see Figures 5, S3, S4 and S5). Photoexcitation of 1-H forms the corresponding excited state that
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serves as a strong electron donor (Eox = -2.71 to -2.88 V (Table S5).18 Thermodynamically and
1/2
thus kinetically favored SET from (1-H)* to the sulfonyl substrate R–SO2R’ affords an aryloxy
radical BIH–ArO• (12) and the sulfonyl radical anion [R–SO2R’]•–,19 which then undergoes N-S or
–
•
C-S bond cleavage to produce the two possible radical and anion pairs R• / R’SO2 or R– / R’SO2
depending on the structure of the substrate.9d Finally, hydrogen atom transfer (HAT) from BIH–
ArO• to radicals R• gives the reduced product R–H and biradical BI•–ArO• (13), the latter of which
undergoes intramolecular SET to reform BI+–ArO–.
Scheme 1. Plausible Mechanism for Photocatalyzed Desulfonylation of Sulfonyl Substrates
Promoted by BI+–ArO– (1) with Hydride Donor Reagents
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hydride
donor
Me
N
Me
N
Me
H–
+H+
N
+
N
H
H
O–
OH
N
N
‒H+
O–
Me
Me
Me
BI+– ArO– (1)
BIH– ArO– (1-H)
BIH– ArOH (1-HH)
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h

SET: single electron transfer
intra-SET
HAT: hydrogen atom transfer
HAT
SET
Me
N
Me
N
R• / R’SO2•
R– SO2R’
(1-H)*
H
N
N
O•
[R– SO2R’]•–
R– H / R’SO2H
O
Me
Me
BIH– ArO• (12)
BI•– ArO• (13)
R•/– / R’SO2
– /•
We previously demonstrated that the photoexcited state of BIH–NapOH (1a-HH) is capable of
promoting desulfonylation reactions and simultaneous formation of BI+–NapO– (1a).9d This
observation suggested the possibility that catalytic amounts of 1a-HH and stoichiometric amounts
of hydride reagents could promote photochemical desulfonylation reactions of sulfonamides if
in-situ generated 1a is converted to BIH–NapO– (1a-H) by hydride reduction. To assess this
proposal, detosylation reactions of 2a and 4 were carried out by using 1a-HH (10 mol%), NaBH4
(1.2 equiv) and Xe or LED irradiation (Table 3). As expected, this protocol was effective in
promoting transformation of 2a to 3a although a longer irradiation time was required than for the
protocol using betaine catalyst 1a (compare entry 2 in Table 3 to entry 1 in Table 1). Moreover, the
presence of bases such as K2CO3 and t-BuOK leads to significant acceleration of the reactions
(compare entry 1 to entry 3 for Xe, compare entry 4 to entries 5 and 6 for LED). Also, prolonged
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irradiation leads to complete reaction while a lower quantity of t-BuOK leads to a higher yield of 3a
(compare entry 7 to entry 8). Similarly, 4 undergoes desulfonylation to form 5 in high yield by
using this modified photocatalytic protocol whose performance is comparable to the original one
(compare entry 9 to entry 2 in Table 2). This protocol was also applied to 10a to produce 11a
although the reaction does not go to the completion, which is again similar to the observation
obtained by the protocol using 1a (compare entry 10 to entry 16 in Table 2).
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Table 3. Photoreductive desulfonylation of N-sulfonyl-indole 2a, -amide 4 and
a
-sulfonylketone 10a promoted by catalytic BIH–NapOH (1a-HH) with NaBH4
hydride base
light
irradiation conv of 2a, yield of 3a,
4, 10a (%)b 5, 11a (%)b,c
entry substrate
donor
(equiv)
source time (h)
1
2
3
4
5
6
7
8
9
10
2a
2a
2a
2a
2a
2a
2a
2a
4
NaBH4
NaBH4
-
-
Xe
Xe
1
36
32 (89)
100
3
100
100
27
NaBH4 t-BuOK (1.0) Xe
1
95
NaBH4
-
LED
LED
1
22 (81)
42 (97)
72 (96)
80
NaBH4 K2CO3 (1.0)
1
43
NaBH4 t-BuOK (1.0) LED
NaBH4 t-BuOK (1.0) LED
NaBH4 t-BuOK (0.5) LED
1
75
2.5
2.5
1
100
100
100
71
98 [84]d
NaBH4
-
LED
88
10a
PicBH3
-
LED
2.5
63 (89)
aSubstrate (0.10 mmol), 1a-HH (10 mol%), hydride donor (1.2 equiv), DMSO (1.0 mL); 500 W
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Xe-lamp ( > 390 nm) or 7.3 W LED. bDetermined by using 1H NMR. cYields in the parentheses
are based on conversion. dIsolated by using column chromatography.
5
6
7
8
9
CONCLUSION
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In the investigation described above, we showed that benzimidazolium aryloxides (BI+–ArO–)
act as photocatalysts in cooperation with stoichiometric hydride donor reagents (NaBH4,
NaCNBH3, Me4NBH4 as well as picoline borane and pinacol borane) for desulfonylation reactions
of N-sulfonyl-indoles, -amines, and -amides, and -sulfonylketones. While typical photocatalysts
for reduction reactions simply behave as electron donors,5,6 the photocatalytic system newly
developed in this effort is unique in that the betaine BI+–ArO– accepts hydride from the reducing
agent in situ to form BIH–ArO–, which serves as both an electron and hydrogen atom donor in the
visible light irradiation induced catalytic cycle. Finally, a modified protocol was developed so that
the more easily prepared BIH–ArOH is used as a photocatalyst along with a stoichiometric hydride
donor to promote the photochemical desulfonylation process.
EXPERIMENTAL SECTION
1
General Methods. H and 13C{1H} NMR spectra were recorded on CDCl3, DMSO-d6 and
1
CD3CN solutions with tetramethylsilane (Me4Si) as an internal standard at 400 MHz for H NMR
13
13
and 100 MHz for C NMR. Proton-decoupled C NMR data are reported. High resolution mass
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spectra (HRMS) were recorded on an electrospray ionization (ESI) Orbitrap spectrometer.
Uncorrected melting points are reported. Oxidation and reduction potentials in
MeCN were measured using cyclic voltammetry and a previously described procedure.5d
Calibration of the potentials were performed using the formal potentials of ferrocene/ferrocenium
couple, which are 0.067 V and 0.442 V versus Ag/AgNO3 and SCE, respectively. Half-wave
potentials (E1/2) reported in the manuscript were obtained from the peak potentials by subtracting or
adding 0.029 V. Light sources for photoreactions were a 500 W Xe lamp with glass filter L-42 ( >
390 nm), 7.3 W and 10.8 W household white LED bulbs. Column chromatography was performed
with silica gel. Anhydrous solvents for photoreactions were obtained as follows. CH2Cl2 and PhCH3
were purified in a same manner by the treatment with H2SO4, water, 5% NaOH, water, and CaCl2
and then distilled over CaH2. MeCN was distilled over P2O5 and subsequently distilled with K2CO3.
THF was distilled over sodium-benzophenone under N2. Anhydrous DMF, DMSO, and MeOH
were purchased and used without distillation. Other reagents and solvents were used without further
purification.
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Preparation of benzimidazolines. 1,3-Dimethyl-2-hydroxyarylbenzimidazolines 1a-HH,9a
1b-HH20 and 1c-HH20 are known compounds. 1d-HH and 1e-HH were prepared by using the
procedure reported for preparation of 1a-HH, 1b-HH and 1c-HH. Preparation and spectroscopic
data of 1d-HH and 1e-HH are described below.
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Synthesis of 1,3-dimethyl-2-(4-hydroxy-3,5-dimethylphenyl)benzimidazoline (1d-HH). To a N2
prepurged Et2O (10 mL) containing N,N’-dimethyl-o-phenylenediamine (1.41 g, 9.98 mmol) with
molecular sieves 4A (~5 g) seated in ice-water bath was added 3,5
dimethyl-4-hydoroxybenzaldehyde (1.65 g, 10.98 mmol, 1.1 equiv) in Et2O (70 mL). The resulting
mixture was stirred for 7.5 h in ice-water bath and then filtered. The yellow solid obtained after
evaporation of the filtrate was subjected to by column chromatography, giving 1d-HH as a yellow
solid (1.47 g, 5.5 mmol, 55%); mp 157-158 °C; 1H NMR (400 MHz, CDCl3)  7.18 (s, 2H), 6.73–
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13
6.71 (m, 2H), 6.45–6.43 (m, 2H), 4.76 (s, 1H), 4.73 (br s, 1H), 2.55 (s, 6H), 2.28 (s, 6H); C{1H}
NMR (100 MHz, CDCl3)  153.1, 142.3, 130.5, 129.1, 123.1, 119.4, 105.9, 94.0, 33.3, 16.1;
HRMS (ESI) m/z calcd for C17H19N2O [M – H] 267.1492, found 267.1502.
Synthesis of 1,3-dimethyl-2-(3-hydroxyphenyl)benzimidazoline (1e-HH). To a N2 prepurged
Et2O (10 mL) containing N,N’-dimethyl-o-phenylenediamine (3.10 g, 20 mmol) with molecular
sieves 3A (~10 g) seated in ice-water bath was added 3-hydoroxybenzaldehyde (2.69 g, 22 mmol,
1.1 eq.) in Et2O (40 mL). The resulting mixture was stirred for 6.5 h in ice-water bath and then
filtered. The yellow solid obtained after evaporation of the filtrates was washed with EtOH giving
1
1e-HH as a yellow solid (3.30 g, 13.7 mmol, 69%); mp 116.5-117 °C; H NMR (400 MHz,
CD3CN)  7.27 (t, J = 7.8 Hz, 1H), 7.04–6.99 (m, 2H), 6.86 (ddd, J = 8.0, 2.4, 0.8 Hz, 1H), 6.67–
6.63 (m, 2H), 6.46–6.41 (m, 2H), 4.78 (s, 1H), 2.51 (s, 6H), hydroxy proton peak is not observed;
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13C{1H} NMR (100 MHz, CDCl3)  156.0, 142.1, 130.5, 129.8, 121.6, 119.5, 116.6, 115.3, 105.9,
93.8, 33.4; HRMS (ESI) m/z calcd for C15H15N2O [M – H] 239.1179, found 239.1187.
8
9
Preparation
of
benzimidazolium
aryloxides.
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1,3-Dimethyl-2-(2-naphthox-1-yl)-benzimidazolium 1a is a known compound and thus
benzimidazolium phenoxides 1b, 1c, 1d and 1e were prepared by using the procedure reported for
1a.6k
Synthesis of 1,3-dimethyl-2-(2-phenox-1-yl)benzimidazolium (1b). A mixture of 1b-HH (477
mg, 2.0 mmol) and 2-bromoacetophenone (616 mg, 3 mmol, 1.5 equiv) in THF (20 mL) was stirred
at room temperature for 15 h. Precipitates formed by the addition of Et2O (ca. 20 mL) were
collected
by
filtration.
The
solid,
which
was
tentatively
assigned
as
1,3-dimethyl-2-(2-hydroxy-1-phenyl) benzimidazolium bromide, was crystallized from MeOH to a
1
give colorless solid (510 mg, 1.60 mmol, 80%); mp > 300 °C; H NMR (400 MHz, DMSO-d6)
 8.12–8.09 (m, 2H), 7.78–7.73 (m, 2H), 7.68–7.64 (m, 2H), 7.21–7.15 (m, 2H), 3.87 (s, 6H). Then,
a MeOH (10.6 mL) containing KOH (95.4 mg, 1.7 mmol, 2.3 eq.) was added to the bromide (236
mg, 0.74 mmol). The resulting mixture was stirred at room temperature for 1 h and then extracted
with CH2Cl2 (20 mL × 10) after addition of water (30 mL). The extract was washed with brine and
dried over anhydrous MgSO4. The residue obtained by concentration was crystallized from MeOH–
Et2O to give 1,3-dimethyl-2-(2-phenox -1-yl) benzimidazolium (1b) (91.8 mg, 0.385 mmol, 52%).
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Yellow solid; mp 252.5-254 ℃; H NMR (400 MHz, DMSO-d6)  7.97–7.23 (m, 2H), 7.62–7.60
5
6
7
(m, 2H), 7.17–7.10 (m, 2H), 6.42 (d, J = 8.8 Hz, 1H), 6.20 (t, J = 7.2 Hz, 1H), 3.86 (s, 6H);
8
9
13C{1H}
NMR
(100
MHz,
DMSO-d6)
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          HRMS
(ESI) m/z calcd
for
C15H15N2O [M + H]+ 239.1179, found 239.1171.
Synthesis of 1,3-dimethyl-2-(4-phenox-1-yl)benzimidazolium (1c). A mixture of 1c-HH (1.49
g, 6.19 mmol) and 2-bromoacetophenone (1.84 mg, 9.29 mmol, 1.5 equiv) in THF (30 mL) was
stirred at room temperature for 3.5 h. The solid obtained by concentration was washed with Et2O to
give
colorless
solid
which
was
tentatively
assigned
as
1,3-dimethyl-2-(4-hydroxy-1-phenyl)benzimidazolium bromide (1.73 g, 5.42 mmol, 88%); mp
285-286.5 °C; 1H NMR (400 MHz, DMSO-d6)  8.10–8.07 (m, 2H), 7.74–7.69 (m, 4H), 7.11 (d, J
= 8.8 Hz, 2H), 3.89 (s, 6H). Then, a MeOH (50 mL) containing KOH (334 mg, 5.95 mmol, 1.1
equiv) was added to the bromide (1.73 mg, 5.42 mmol). The resulting mixture was stirred at room
temperature for 1 h. The residue obtained by concentration was washed with water and crystallized
from CH3CN to give 1,3-dimethyl-2-(4-phenox -1-yl)benzimidazolium (1c) (737 mg, 3.09 mmol,
57%). Pale yellow solid; mp 282.0-283.0 °C; 1H NMR(400 MHz, DMSO-d6)  7.88–7.85 (m, 2H),
7.58–7.55 (m,2H), 7.27 (d, J = 8.8 Hz, 2H), 6.28 (d, J = 8.4 Hz, 2H), 3.89 (s, 6H); 13C{1H}
NMR(100
MHz,
DMSO-d6)
         HRMS
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(ESI) m/z calcd for C15H15N2O [M + H]+ 239.1179, found 239.1172.
4
5
6
7
8
9
Synthesis of 1,3-dimethyl-2-(3,5-dimethyl-4-phenox-1-yl)benzimidazolium (1d). A mixture of
1d-HH (460 mg, 1.71 mmol) and 2-bromoacetophenone (510 mg, 2.56 mmol, 1.5 equiv) in THF
(100 mL) was stirred at room temperature for 6.5 h. The solid obtained by concentration was
washed with Et2O to give colorless solid which was tentatively assigned as
1,3-dimethyl-2-(3,5-dimethyl-4-hydroxy-1-phenyl)benzimidazolium bromide (352 mg, 1.01 mmol,
60%); mp > 300 °C; 1H NMR (400 MHz, DMSO-d6)  8.09–8.06 (m, 2H), 7.73–7.71 (m, 2H), 7.45
(s, 2H), 3.89 (s, 6H). Then, a MeOH (10 mL) containing KOH (61.7 mg, 1.11 mmol, 1.1 equiv) was
added to the bromide (352 mg, 1.01 mmol). The resulting mixture was stirred at room temperature
for 1 h. The residue obtained by concentration was washed with water and crystallized from
CH3CN to give 1,3-dimethyl-2-(3,5-dimethyl-4-phenox -1-yl)benzimidazolium (1d) (234 mg, 0.88
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mmol, 87%). Pale yellow solid; mp 157.0-158.0 °C; H NMR(400 MHz, DMSO-d6)  7.83–7.79
(m, 2H), 7.55–7.51 (m, 2H), 7.14 (s, 2H), 3.88 (s, 6H), 1.99 (s, 6H); 13C{1H} NMR(100 MHz,
DMSO-d6)
            HRMS
(ESI) m/z calcd for C17H19N2O [M + H]+ 267.1484, found 267.1492.
Synthesis of 1,3-dimethyl-2-(3-phenox-1-yl)benzimidazolium (1e). A mixture of 1e-HH (1.55
g, 6.44 mmol) and 2-bromoacetophenone (1.93 g, 9.70 mmol, 1.5 equiv) in THF (50 mL) was
stirred at room temperature for 8 h. Precipitates formed by the addition of Et2O (ca. 50 mL) were
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collected
by
filtration.
The
solid,
which
was
tentatively
assigned
as
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6
7
1,3-dimethyl-2-(3-hydroxy-1-phenyl)benzimidazolium bromide, was crystallized from MeOH to
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give colorless solid (1.61 g, 5.03 mmol, 78%); mp > 300 °C; H NMR (400 MHz, DMSO-d6)
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 10.29 (s, 1H) 8.13–8.11 (m, 2H), 7.78–7.74 (m, 2H), 7.57 (t, J = 8.0 Hz, 1H), 7.28–7.19 (m, 3H),
3.88 (s, 6H). Then, a MeOH (20.8 mL) containing KOH (105 mg, 1.87 mmol, 1.0 equiv) was added
to the bromide (603 mg, 1.89 mmol). The resulting mixture was stirred at room temperature under
N2 for 1 h. Precipitated solid containing KBr by the addition of Et2O (ca. 20 mL) was collected by
filtration and washed with CH3CN (ca. 5 mL x2). To the filtrate was added PhCH3 (20 mL), and the
appeared
solid
was
filtered
and
rinsed
with
Et2O
to
give
1,3-dimethyl-2-(3-phenox-1-yl)benzimidazolium (1e). (159 mg, 0.669 mmol, 35%). Pale yellow
solid: mp 167.5-169.0 °C; 1H NMR (400 MHz, DMSO-d6)  8.08–8.05 (m, 2H), 7.73–7.71 (m, 2H),
7.32 (t, J = 8.0 Hz, 1H), 6.90 (d, J = 8.4 Hz, 1H), 6.85 (s, 1H), 6.75 (d, J = 7.6 Hz, 1H), 3.89 (s,
1H);
13C{1H}
NMR(100
MHz,
DMSO-d6)
             HRMS
(ESI) m/z calcd for C15H15N2O [M + H]+ 239.1179, found 239.1172.
Preparation of substrates. N-Sulfonyl indoles 2a,9d 2b,9d 2c,9d N-tosyl benzamide 4,9d
N,N-diphenyl-N-tosylamine 6,9d N,N-dibenzyl-N-tosylamine 8,9d -sulfonyl ketones 10a,6k and
10b,6k which are known compounds, were prepared by using the reported procedures.
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Photoreaction Procedure. Solutions containing substrates 2, 4, 6, 8, or 10 with 1 and a
hydride donor in Pyrex test tubes (1.4 cm diameter) were irradiated with a Xe lamp or white LEDs
at room temperature. The test tubes were immersed in a water bath for the reactions using Xe
klamp. A typical procedure is described below. An appropriate solvent (1.0 mL) containing 1a (2.9
mg, 10 mol %), NaBH4 (5.0 mg, 0.12 mmol), and 2a (32.9 mg, 0.10 mmol) was purged with N2 for
10 min and then irradiated with a Xe lamp through L-42 glass filter. The photolysate was diluted
with water (30 mL) and extracted with EtOAc (20 mL × 3). The combined extracts were washed
with water (30 mL × 2), brine (30 mL), dried over anhydrous MgSO4, and concentrated in vacuo to
give a residue. The conversion of 2a and the yield of 3a were determined by using 1H NMR
analysis of the residue with triphenylmethane as an internal reference in CDCl3. Photoproducts 3a,9d
59d and 11a6l are known compounds while 3c, 7, 9 and 11b are commercial materials. Preparative
photoreactions of selected substrates such as 2a, 4, 6 and 10a with 1a and NaBH4 or picoline borane
(PicBH3) were performed (see below).
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Preparative photoreaction of 2a with 1a. Irradiation of 1a (2.9 mg,10 mol %), NaBH4 (5.0 mg,
0.12 mmol), and 2a (32.9 mg, 0.10 mol) in DMSO (1.0 mL) was carried out under the same
condition as that for entry 10 of Table 1. The reaction mixture obtained after same work-up
procedure described above was subjected to column chromatography using EtOAc and n-C6H14
1
(2/1) to give 3a (15.7 mg, 0.0896 mmol, 90%). Colorless powder solid; H NMR (400 MHz,
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CDCl3)  8.85 (br s, 1H), 7.71–7.68 (m, 1H), 7.43–7.41 (m, 1H), 7.33 (td, J = 7.2, 1.2 Hz, 1H),
7.23–7.22 (m, 1H), 7.16 (td, J = 7.6, 0.8 Hz, 1H), 3.95 (s, 3H).
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8
9
Preparative photoreaction of 4 with 1a. Irradiation of 1a (2.9 mg,10 mol %), NaBH4 (5.0 mg,
0.12 mmol), and 4 (36.5 mg, 0.10 mol) in DMSO (1.0 mL) was carried out under the same
condition as that for entry 2 of Table 2. The reaction mixture obtained after same work-up
procedure described above was subjected to column chromatography using EtOAc and n-C6H14
(2/1) to give 5 (18.1 mg, 0.0857 mmol, 86%). Colorless powder solid; 1H NMR (400 MHz, CDCl3)
 7.80–7.78 (m, 2H), 7.52–7.47 (m, 1H), 7.44–7.40 (m, 2H), 7.36–7.34 (m, 4H), 7.32–7.27 (m, 1H),
6.55 (br s, 1H), 4.66– 4.63 (m, 2H).
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Preparative photoreaction of 6 with 1a. Irradiation of 1a (2.9 mg,10 mol %), NaBH4 (5.0 mg,
0.12 mmol), and 6 (32.3 mg, 0.10 mol) in DMSO (1.0 mL) was carried out under the same
condition as that for entry 12 of Table 2. The reaction mixture obtained after same work-up
procedure described above was subjected to column chromatography using EtOAc and n-C6H14
1
(2/1) to give 7 (15.6 mg, 0.0922 mmol, 92%). Pale yellow powder solid; H NMR (400 MHz,
CD3CN)  7.28 (t, J = 8.0 Hz, 2H), 7.10 (dd, J = 8.4, 0.8 Hz, 4H), 6.91 (tt, J = 7.4, 1.0 Hz, 2H),
6.66 (br s, 1H).
Preparative photoreaction of 10a with 1a. Irradiation of 1a (2.9 mg,10 mol %), PicBH3 (15.1
mg, 0.12 mmol), and 10a (35.0 mg, 0.10 mol) in DMSO (1.0 mL) was carried out under the same
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condition as that for entry 15 of Table 2. The reaction mixture obtained after same work-up
4
5
6
7
procedure described above was subjected to column chromatography using EtOAc and n-C6H14
8
9
1
(1/2) to give 11a (19.8 mg, 0.0942 mmol, 94%). Colorless powder solid; H NMR (400 MHz,
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CD3CN)  7.99–7.97 (m, 2H), 7.61 (t, J = 7.4 Hz, 1H), 7.50 (t, J = 7.8 Hz, 2H), 7.30–7.29 (m, 4H),
7.22–7.17 (m, 1H), 3.35 (t, J = 7.6 Hz, 2H), 3.01 (t, J = 7.4 Hz, 2H).
Preparative photoreaction of 2a with 1a-HH. Irradiation of 1a-HH (2.9 mg,10 mol %),
NaBH4 (5.0 mg, 0.12 mmol), t-BuOK (5.6 mg, 0.5 mmol), and 2a (32.9 mg, 0.10 mol) in DMSO
(1.0 mL) was carried out under the same condition as that for entry 8 of Table 3. The reaction
mixture obtained after same work-up procedure described above was subjected to column
chromatography using EtOAc and n-C6H14 (1/6) to give 3a (14.7 mg, 0.0839 mmol, 84%) Colorless
1
powder solid; H NMR (400 MHz, CDCl3)  8.84 (br s, 1H), 7.70 (dd, J = 8.0, 0.8 Hz, 1H), 7.42
(dd, J = 8.4, 0.8 Hz, 1H), 7.33 (td, J = 7.6, 0.8 Hz, 1H),7.23–7.22 (m, 1H), 7.16 (td, J = 7.6, 1.2 Hz,
1H), 7.23–7.22 (m, 1H), 3.95 (s, 3H).
Density Functional Theory Calculations. Calculations were performed using the Gaussian
09 package.16 Geometry optimizations were performed on ground state structures using the
restricted B3LYP functional with the 6-31+G(d) basis set. In addition, frequency calculations were
performed on all the optimized structures to confirm the absence of imaginary frequencies. The
optimized structures and molecular orbitals were visualized with GaussView 5.0.9.
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ASSOCIATED CONTENT
Supporting Information
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The Supporting Information is available free of charge on the ACS Publications website at DOI:
Data of absorption spectra, cyclic voltammograms, additional photoreactions, DFT calculations, 1H
NMR charts of selected photoreaction products, 1H NMR charts of benzimidazolium bromides and
1H and 13C NMR spectra of new 1 and 1-HH (PDF).
AUTHOR INFORMATION
Corresponding Author
*E-mail for E.H.: ehase@chem.sc.niigata-u.ac.jp.
ORCID
Notes
The authors declare no competing financial interest.
ACKNOWLEDGEMENTS
This manuscript is dedicated to the memory of the late Professor Keiji Okada (Osaka City
University) who is one of pioneers for synthetic application of photoredox catalysts. This study was
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partially supported by JSPS KAKENHI Grants (JP 16K05689 and JP 19K05435 for E.H).
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REFERENCES
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(1) Representative book chapters and reviews for early examples of PET reactions. (a)
Photoinduced Electron Transfer, Fox, M. A.; Chanon, M., Eds.; Elsevier: Amsterdam, 1988,
Parts A–D. (b) Kavarnos, G. J. Fundamental of Photoinduced Electron Transfer; VCH: New
York, 1993. (c) Hasegawa, E. Characteristic Reactivities of Some Rearrangeable Ketyl
Radicals Generated through Photoinduced Electron Transfer Processes. J. Photosci. 2003, 10,
61–69. (d) Oelgemöller, M.; Bunte, J. O.; Mattay, J. Synthetic Organic Photochemistry in
Molecular and Supramolecular Photochemistry, Griesbeck, A. G.; Mattay, J. Eds.; Marcel
Dekker: New York, 2005; Vol. 12, pp 269–297. (e) Cossy, J.; Belotti, D. Generation of Ketyl
Radical Anions by Photoinduced Electron Transfer (PET) between Ketones and Amines.
Synthetic Applications. Tetrahedron 2006, 62, 6459–6470. (f) Floreancig, P. E. Development
and Applications of Electron-Transfer-Initiated Cyclization Reactions. Synlett 2007, 191–203.
(g) Ravelli, D.; Dondi, D.; Fagnoni, M.; Albini, A. Photocatalysis. A Multi-faceted Concept
for Green Chemistry. Chem. Soc. Rev. 2009, 38, 1999–2011. (h) Cho, D. W.; Yoon, U. C.;
Mariano, P. S. Studies Laedaing to the Development of a Single-Electron Transfer (SET)
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