Organic photoredox catalyst with substrate-capture ability: A perylene derivative bearing urethane moiety for reductive coupling of ketones and aldehydes under visible light

Article abstract of DOI:10.1246/cl.171160

A perylene derivative bearing a urethane moiety served as an efficient photoredox catalyst for the reductive coupling of ketones and aldehydes under visible light, implicating that the urethane moiety captured substrates through hydrogen bonds to lower the LUMO levels of the captured substrates, thus promoting single electron transfer from the reductant anion radical of the perylene moiety to the substrates.

Full text of DOI:10.1246/cl.171160

Advance Publication Cover Page
Organic Photoredox Catalyst with Substrate-capture Ability: A Perylene Derivative Bearing
Urethane Moiety for Reductive Coupling of Ketones and Aldehydes under Visible Light
Shusuke Okamoto, Hiroki Tsujioka, and Atsushi Sudo*
Advance Publication on the web January 10, 2018
doi:10.1246/cl.171160
© 2018 The Chemical Society of Japan
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Publication manuscripts.

Organic Photoredox Catalyst with Substrate-capture Ability: A Perylene Derivative Bearing
Urethane Moiety for Reductive Coupling of Ketones and Aldehydes under Visible Light
Shusuke Okamoto,1 Hiroki Tsujioka1 and Atsushi Sudo*1
1Department of Applied Chemistry, Faculty of Science and Engineering,
Kindai University, 11-6 Kowakae, Higashi Osaka, Osaka 577-8502, Japan
E-mail: asudo@apch.kindai.ac.jp
1
2
3
4
5
6
7
8
9
A perylene derivative bearing a urethane moiety
served as an efficient photoredox catalyst for the reductive
coupling of ketones and aldehydes under visible light,
implicating the urethane moiety captured substrates through
hydrogen bonds to lower the LUMO levels of the captured
substrates, thus promoting single electron transfer from the
reductant anion radical of the perylene moiety to the
substrates.
50 under visible light using a white LED.16 In the reaction,
51 a single electron transfer from the radical anion of
52 perylene to the substrate gives the corresponding anion
53 radicals, and their homocoupling affords the
54 corresponding 1,2-diols and 1,2-diamines. The
55 photoredox catalysis using perylene is simple and metal
56 free; however, the yields of the products are moderate,
57 particularly in the reactions of ketones and aldehydes
58 with relatively high LUMO levels.
10 Keywords: Photoredox catalysis, Perylene derivative,
11 Reductive coupling
59
To improve the visible light-driven coupling of
60 carbonyl compounds, we envisaged catalysis assisted
61 by hydrogen bonds, which could tether carbonyl
62 compounds to the PRCs non-covalently. Capture and
63 activation of carbonyl compounds by appropriately
64 designed organocatalysts with hydrogen bond donors
12
The reductive coupling of ketones and aldehydes
13 affords vicinal diols, which are attractive precursors for
14 various ligands and chiral auxiliaries.1 These reactions
15 proceed with stoichiometric amounts of metals or low-
16 valent metal compounds with high reduction potentials such
17 as Mg(0),2 Ti(II),3 Zn(0),4 and Sm(II)/Sm(0).5 One-electron
18 reduction of substrates by these metals gives the
19 corresponding radical anions, which are coupled to produce
20 vicinal diols. However, the consumption of stoichiometric
21 amounts of precious metals is a serious issue from economic
22 and environmental viewpoints.
65 have
been
efficiently
utilized
to
achieve
66 enantioselective reactions17-18 and controlled ring-
67 opening polymerizations.19 Recently, an well-
68 constructed asymmetric reaction environment was
69 achieved by designing chiral catalysts bearing a planar
70 π-conjugated wall and acidic arm, which cooperatively
71 captured and facilitated enantioselective reactions.20 In
72 the reductive coupling of aldehydes and ketones using
73 iridium(III) complexes, hydrogen bond activation of the
74 substrates by ammonium salts is postulated.11 Moreover,
75 the efficiency of the coupling of acetophenone was
76 improved by adding Brϕnsted acids.11 In the visible
77 light-driven aza-pinacol cyclization using an
78 iridium(III) complex, chiral phosphates were used as
79 additives to control enantioselectivity.12b
23
To overcome such issues, the use of photoredox
24 catalysts (PRCs) that use visible light as an energy
25 source is a promising strategy. A variety of PRCs,
26 including Ru(II) and Ir(III) complexes and organic dyes,
27 have been employed in various reactions6 such as
28 dehalogenation,7 C-heteroatom bond forming,8 and C-C
29 bond forming.7c, 9 The reductive coupling of carbonyl
30 compounds has also been a target in photoredox
31 systems. For example, the reductive coupling of
32 benzaldehyde using poly(p-phenylene) as a PRC has
33 been reported.10 Ir(III) complexes also drive the
34 coupling of aldehydes, ketones, and imines, forming a
35 variety of 1,2-diols and 1,2-diamines under visible
36 light.11 Other photocatalytic C-C bond forming
37 reactions based on one electron reduction of C=O and
38 C=N bonds have been also reported.12
80
The aforementioned studies motivated us to design
81 a PRC with a hydrogen bond donor that could capture
82 substrates and facilitate electron transfer from the
83 photo-reduced moiety of the catalyst to the substrate.
84 Specifically, we designed a perylene-derivative bearing
85 a urethane moiety as a hydrogen bond donor (Figure 1).
86 The pKa of urethanes is estimated to be approximately
87 13,21 which would be enough low to act as a hydrogen
88 bond donor. Herein, we report the visible light-driven
89 reductive coupling of ketones and aldehydes using the
90 urethane-perylene catalyst.
91
92
93
94
95
96
97
39
Recently, perylene was revealed to catalyse
40 controlled radical polymerizations under visible light,
41 where photo-excited perylene reduces C-Br into C. and
42 Br.-; the resulting perylene cation radical oxidizes Br-
43 into Br., which can recombine with a propagating
44 radical.13 Photo-excited perylene can also be used as a
45 reductant in C-CFnH(3-n) bond forming reactions.14 On
46 the other hand, photo-excited perylene can also be
47 reduced by sacrificial tertiary amines into an anion
48 radical.15 We developed the photocatalytic reductive
49 coupling of aromatic aldehydes, ketones, and imines
98
99
Figure 1. Perylene derivatives for photocatalysis of
reductive coupling of ketones and aldehydes

1
2
3
4
5
6
7
8
9
Urethane-perylene 1 was synthesized by the
reaction of its precursor 3-(hydroxymethyl)perylene22
with tert-butylisocyanate. The details are described in
the Supporting Information (SI). 1 was soluble in a
wide range of organic solvents, presumably owing to
40 than that achieved by using perylene, proving the
41 feasibility of the concept. The yield of diol 3a was
42 improved to approximately 40%. The diastereomers, dl-
43 and meso-ones, formed in an almost 1:1 ratio. In entry 4,
44 in place of the white LED, a 420 nm LED was used.
45 The coupling proceeded efficiently, confirming that 1
46 absorbed blue light to catalyse the coupling, as was
47 expected from its absorption maximum at around 420
48 nm (for the UV-vis spectrum, see Figure S3).
1
the presence of the tert-butyl group. The H- and 13C-
NMR spectra of 1 are shown in Figure S2 in the SI.
The reductive coupling of acetophenone 2a and
benzophenone 2b was performed using perylene or
10 urethane-perylene 1 as PRCs (Scheme 1, Table 1). As
11 the sacrificial electron donor and solvent, N,N-
12 diisopropylethylamine and acetonitrile were used,
13 respectively, because this combination exhibited the
14 best efficiency in the previously reported coupling of
15 benzaldehyde.16a Visible light was applied for 16 h, and
49
To confirm the validity of the design of urethane-
50 perylene
1
as PRC, reductive coupling of
a
51 acetophenone 2a was carried out using perylene and
52 benzyl tert-butylcarbamate (BTBC), where these two
53 components act as the PRC and hydrogen bond donor
54 independently (entry 5). Compared to the reaction
1
16 then the reaction mixture was analyzed via H-NMR to
55 without BTBC (Table 1, entry 2), the conversion of 2a
17 determine the conversion of 2, yield of diol 3, and
18 diastereoselectivity. The yields of alcohols 4 were
19 calculated based on the relative signal intensity of the
56 was improved from 25 to 37%, implying that the
57 urethane moiety of BTBC activated 2a by forming a
58 hydrogen bond. However, this improvement was much
59 less than that achieved using urethane-perylene 1 (Table
1
20 methine proton in the H-NMR spectra. Next, diol 3
21 was isolated by preparative thin layer chromatography
60 1, entry 3), confirming that tethering the perylene and
61 urethane moieties promoted the reaction.
1
22 (PTLC). The H-NMR spectra of the crude products
23 and the 1H- and 13C-NMR spectra of the isolated
24 products are shown in the SI.
62
63
64
65
66
67
68
69
70
71
72
73
74
75
25
Previously, the use of a large amount of perylene
26 (12 mol%) in the reductive coupling of acetophenone
27 was described (Table 1, entry 1).16a Therefore, we
28 explored suitable reaction conditions that would allow
29 us to reduce the amount of perylene. However, when
30 the amount of perylene was reduced to 1 mol%, the
31 conversion of acetophenone was as low as 25%, even
32 when the initial concentration of acetophenone 2a was
33 increased to 100 mM (Table 1, entry 2). Next, we
34 employed urethane-perylene 1 in place of perylene to
35 evaluate its performance as a PRC in the coupling of 2a,
36 expecting that the urethane moiety would capture 2a via
37 hydrogen bonds and activate 2a (entry 3). The 1H-NMR
38 spectrum of the resulting reaction mixture is shown in
39 Figure S6 in the SI. The conversion of 2a was higher
76
77
Scheme 1. Photocatalysis of reductive coupling of
aromatic ketones by perylene derivatives
78
79
Table 1. Visible light-driven reductive coupling of ketonesa
Amount of
PRC/mol%
Conversion of
Yield of
Yield of
Entry
2
PRC
Additive
[2]0/mM
dl : meso of 3b
2 /%b
3/%b
4/%b
Not
determined
1c
2
2a Perylene
12
1
1
None
None
20
(23)d
20 (16)d
43 (38)d
41
(46:54)e
-
0
2a
2a
2a
2a
2b
2b
Perylene
100
100
100
100
100
100
25
57
61
37
49
57
56:44 (49:51)e
3
1
None
52:48 (50:50)e
0
4f
5
1
1
None
59:41
0
Perylene
Perylene
1
1
BTBC (1 mol%)
None
27 (22)d
28 (23)d
45 (38)d
51:49 (49:51)e
0
6
1
-
-
21
12
7
1
None
80
a
1
81
82
83
0.500 mmol of 2 was used, and a white LED (8.5 W) was used for the irradiation of visible light. b Determined by H-NMR analysis of
the reaction mixture. c Reported in ref. 16b. d Yield of 3 isolated by preparative TLC. e Determined by the 1H-NMR analysis of isolated 3a.
f A 420 nm blue LED (6 W) was used for the irradiation of visible light.

1
2
3
4
5
6
7
8
9
The use of 1 in place of perylene resulted in the
improved coupling of benzophenone 2b (entry 6 vs.
entry 7). The photoredox reaction of 2b gave coupling
product 3b and alcohol 4b. The use of perylene resulted
in the formation of 4b in 21%, while 1 resulted in
suppressed formation of 4b, allowing the yield of diol
3b to increase to approximately 40%.
59
60
61
62
63
64
65
Upon confirming the higher performance of 1, as
compared with perylene, as a PRC for the coupling of
66
67
68
69
Scheme 2. Photocatalysis of reductive coupling of
aromatic aldehydes by perylene derivatives
10 ketones, its ability to catalyse the coupling of aldehydes
11 5 was investigated (Scheme 2, Table 2). Previously, the
12 coupling of 4-methoxybenzaldehyde 5a, benzaldehyde
13 5b, and 4-fluorobenzaldehyde 5c was performed using
14 12 mol% of perylene.16b Thus, prior to using urethane-
15 perylene 1 as a PRC, the coupling of 5 was
16 reinvestigated using 1 mol% perylene and 100 mM 5
17 instead of 20 mM. As a result, the corresponding diols 6
18 were obtained in good yields (64%~78%) (entries 1, 3,
19 and 5). The conversions of 5b and 5c were 100%;
20 however, the conversion of 5a was lower than those of
21 5b and 5c, presumably owing to its more electron rich
22 nature.
70 Table 2. Visible light-driven reductive coupling of aldehydesa
Yield
of
6/%b
dl :
meso of
6b
Yield
of
Conversion
of 5 /%b
Entry
5
PRC
7/%b
64
(62)c
69
83:17
(85:15)d
80:20
1
2
5a
5a
5b
5b
5b
5c
5c
Perylene
78
0
9
0
0
0
0
0
1
98
(66)c
(83:17)d
78
56:44
3
Perylene
Perylene
1
100
100
100
100
100
(74)e
71
(55:45)f
54:46
4g
5
(69)e
(53:47)f
23
Next, the use of 1 was investigated in the coupling
24 of 5a (entry 2). Upon replacing perylene with 1, the
25 conversion of 5a was improved from 78% to 98%, and
26 the yield of diol 6a was improved from 64% to 69%,
27 suggesting that 5a would be efficiently captured by the
28 urethane moiety and activated. On the other hand, the
29 conversions of 5b and 5c were 100% even by using
30 pristine perylene, and thus it seemed there was no
31 chance to improve the efficiency further by using 1.
32 However, it turned out that 1 gave increased yields of
33 product diols 6b and 6c (entries 5 and 7), suggesting
34 that unclarified side reactions accompanying the
35 perylene-catalyzed reductive coupling of aldehydes
36 were successfully suppressed in the 1-catalyzed
37 reactions. One possible side reaction is the coupling of
38 the anion radical formed by the one-electron reduction
39 of aldehyde and the radical formed via the one-electron
40 oxidation of the tertiary amine.12a Using 1, the coupling
41 reaction was promoted over the competing side reaction,
42 leading to high yields of 6b (88%) and 6c (77%). Such
43 a high yield of 6b was not achieved by the perylene-
44 catalyzed coupling of benzaldehyde 5b by adding
45 BTBC (entry 4), confirming that the tethering of the
46 urethane and perylene moieties in 1 was indispensable
47 for the achievement of the higher yield in entry 5 than
48 that in entry 3.
88
56:44
(86)e
69
(53:47)f
58:42
6
Perylene
1
(64)c
(63:37)d
77
(71)c
64:36
(69:31)d
7
71
a 0.500 mmol of 5 was used, and an 8.5 W white LED was used
72 for the irradiation of visible light. Determined by 1H-NMR
b
c
73 analysis of the reaction mixture.
Yield of 6 isolated by
74 preparative TLC. d Determined by 1H-NMR analysis of isolated 6.
e
f
75
Yield of 8b, diacetate of 6b, isolated by preparative TLC.
76 Determined by 1H-NMR analysis of isolated 8b. g The reaction
77 was carried out in the presence of BTBC (1 mol%).
78
79
80
81
82
83
84
85
86
87
88
89
90
91
92
93
94
95
96
97
49
Figure 2 describes possible mechanisms for the
50 photocatalysis. As previously reported, perylene can be
51 excited by visible light, and one electron can be
52 transferred from tertiary amines added as sacrificial
53 electron donors to excited perylene. Analogously, the
54 perylene moiety of 1 excited by visible light abstracts
55 an electron from the tertiary amine, leading to the
56 formation of 1.-, a strong reductant. From the radical
57 anion, a single electron transfer (SET) to substrate takes
58 place, giving the corresponding radical anion of the
98
99
Figure 2. Photocatalysis of reductive coupling of
ketones and aldehydes by urethane-perylene 1.

57
58
59
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63
64
65
66
67
68
69
70
71
72
73
74
75
76
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80
81
4
5
6
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The cation radicals of the tertiary amine act as proton
donors. As discussed above, the use of 1 led to the
higher conversions of some of the substrates such as
acetophenone and 4-methoxybenzaldehyde with
relatively high LUMO levels (for DFT calculations of
the LUMO levels, see SI); thus, capturing them through
hydrogen bonds lowered their LUMO levels.
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The pKa value was calculated using Advanced Chemistry
Development (ACD/Labs) Software V11.02.
7
Another significant aspect of the use of 1 as a PRC,
10 is that it facilitated higher yields of the coupling
11 products in reactions of substrates with lower LUMO
12 levels such as benzophenone, benzaldehyde, and 4-
13 fluorobenzaldehyde. It would be reasonable to postulate
14 a faster proton transfer from the urethane moiety to the
15 radical anions formed from these substrates. Upon
16 protonation, the radical anions can be transformed into
17 radical species without a negative charge, which can
18 undergo the coupling reaction more easily. Another
19 explanation can be based on the presence of hydrogen
20 bonds between the urethane moieties of 1. Such
21 interactions facilitate the aggregation of 1, which would
22 lead to the increased probability of coupling of radical
23 anions.
8
9
82 10
83
84 11
85
24
In summary, a new PRC bearing a visible light-
25 responsive perylene moiety and a urethane moiety was
26 synthesised and employed in the visible light-driven
27 reductive coupling of ketones and aldehydes. The
28 urethane moiety was introduced to capture and activate
29 the substrates through hydrogen bonds for efficient
30 electron transfer from the anion radical of the perylene
31 moiety to the substrates. The improved conversions of
32 substrates with higher LUMOs such as acetophenone
33 and 4-methoxybenzaldehyde prove that the urethane
34 moiety captured these substrates as expected. Further
35 investigations into the role of the urethane moiety will
36 be continued to achieve appropriate molecular designs
37 of perylene derivatives as PRCs.
86 12
87
88
89
90
91 13
92
93
94 14
95 15
96
97 16
98
99
100 17
101
38
102
39 Acknowledgement
40
103 18
104
We gratefully acknowledge the financial support
41 of the MEXT-supported Program for the Strategic 105
106
42 Research Foundation at Private Universities 2014–2018
43 (no. 26410059), a subsidy from MEXT and Kindai
44 University.
45
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available
on
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