Photoinduced hydroxylation of arylboronic acids with molecular oxygen under photocatalyst-free conditions

Article abstract of DOI:10.1039/c9gc02229e

Photoinduced hydroxylation of boronic acids with molecular oxygen under photocatalyst-free conditions is reported, providing a green entry to a variety of phenols and aliphatic alcohols in a highly concise fashion. This new protocol features photocatalyst-free conditions, wide substrate scope and excellent functional group compatibility.

Full text of DOI:10.1039/c9gc02229e

View Article Online
View Journal
Green
Chemistry
Cutting-edge research for a greener sustainable future
Accepted Manuscript
This article can be cited before page numbers have been issued, to do this please use: Y. Xu, C. Li, X.
Huang, W. Gao, Y. Zhou, M. Liu and H. Wu, Green Chem., 2019, DOI: 10.1039/C9GC02229E.
Volume 20
This is an Accepted Manuscript, which has been through the
Number
May 2018
Pages 1919-2160
9
7
Royal Society of Chemistry peer review process and has been
accepted for publication.
Green
Chemistry
Cutting-edge research for a greener sustainable future
rsc.li/greenchem
Accepted Manuscripts are published online shortly after acceptance,
before technical editing, formatting and proof reading. Using this free
service, authors can make their results available to the community, in
citable form, before we publish the edited article. We will replace this
Accepted Manuscript with the edited and formatted Advance Article as
soon as it is available.
You can find more information about Accepted Manuscripts in the
Information for Authors.
Please note that technical editing may introduce minor changes to the
text and/or graphics, which may alter content. The journal’s standard
Terms & Conditions and the Ethical guidelines still apply. In no event
shall the Royal Society of Chemistry be held responsible for any errors
or omissions in this Accepted Manuscript or any consequences arising
from the use of any information it contains.
ISSN 1463-9262
PAPER
Paul T. Anastas et al.
The Green ChemisTREE: 20 years after taking root with the 12
principles
rsc.li/greenchem

Please do not adjust margins
Page 1 of 5
Green Chemistry
View Article Online
DOI: 10.1039/C9GC02229E
COMMUNICATION
Photoinduced hydroxylation of arylboronic acids with molecular
oxygen under photocatalyst-free conditions
Received 00th January 20xx,
Yu-Ting Xu, Chen-Yuan Li, Xiao-Bo Huang, Wen-Xia Gao, Yun-Bing Zhou,* Miao-Chang Liu* and
Hua-Yue Wu
Accepted 00th January 20xx
DOI: 10.1039/x0xx00000x
Photoinduced hydroxylation of boronic acids with molecular Table 1 Optimization of reaction conditionsa
oxygen under photocatalyst-free conditions is reported, providing
a green entry to a variety of phenols and aliphatic alcohols in a
B(OH)2
highly concise fashion. This new protocol features photocatalyst-
solvent, rt
O2
light, additive
OH
free conditions, wide substrate scope and excellent functional
1a
1b
group compatibility.
entry
1
light source
UV lamp
UV lamp
UV lamp
UV lamp
UV lamp
UV lamp
UV lamp
UV lamp
UV lamp
UV lamp
UV lamp
UV lamp
UV lamp
UV lamp
filament lamp
green LED
blue LED
dark
additive
--
solvent
yield(%)
23
87
40
53
77
41
23
33
92
82
83
65
58
0
Phenols and their derivatives represent an important class of
compounds because they are structural motifs in many in
natural products and biologically active compounds, and
versatile synthetic intermediates.1 For this reason,
considerable attention has been aroused in the construction of
phenols and their derivatives.2 One of the most effective
established strategies toward their synthesis phenols is the
hydroxylation of arylboronic acids. Pioneering work on the
conditions for the hydroxylation of arylboronic acids focused
on the use of transition metals3 with the requirement of a
strong base in some case. Alternatively in the absence of
transition metals, the use of stoichiometric strong oxidants
such as hydrogen peroxide,4 PhI(OAc)2,5 benzoquinone,6
mCPBA,7 TBHP,8 NaBO3,9 oxone10 and amine oxide11 enabled
directly hydroxylation of arylboronic acids to access phenols. In
addition, organic electrochemistry as an efficient synthetic
technology has been applied in the hydroxylation of boronic
acids.12
On the other hand, photoredox catalysis has emerged as a
powerful strategy for construction of C-C and C-heteroatom
bonds in the organic synthesis.13 Groundbreaking effort on
light-promoted aerobic oxidative hydroxylation of arylboronic
acids to phenols in the presence of Ru(bpy)3Cl2 was made by
Xiao’s group.14 Subsequently, much attention has been
focused in the development of photocatalysts for
photocatalytic oxidative hydroxylation of arylboronic acids.15
Nevertheless, most of these photocatalysts suffered from
tedious synthesis and expensive cost. In this regard, these
DMF
2
3
Et3N
Et3N
DMF
dioxane
THF
4
Et3N
5
Et3N
CH3CN
6
Et3N
toluene
DCM
7
Et3N
8
Et3N
DMSO
9
Et3N
2-MeTHF
2-MeTHF
2-MeTHF
2-MeTHF
2-MeTHF
2-MeTHF
2-MeTHF
2-MeTHF
2-MeTHF
2-MeTHF
10
11
12
13b
14c
15
16
17
18
DIPEA
(Me)2EtN
n
(Me)2 BuN
Et3N
Et3N
Et3N
Et3N
Et3N
Et3N
10
83
80
0
aReaction conditions: 1a (0.3 mmol), O2 (1 atm), light source
(15 W), additive (0.45 mmol), solvent (4 mL), rt, 24 h, isolated
yields. bUnder the air atmosphere. cUnder the N2 atmosphere.
issues can be solved by photocatalyst-free aerobic
hydroxylation of arylboronic acids, which represents an
attractive and cost-effective strategy for building phenols.
Herein, we disclosed a photocatalyst-free method for light-
promoted aerobic hydroxylation of arylboronic acids for the
first time, with triethylamine being used as an additive.
College of Chemistry and Materials Engineering, Wenzhou University, Wenzhou
325035, China. E-mail: zyb@wzu.edu.cn; mcl@wzu.edu.cn
Electronic Supplementary Information (ESI) available: [details of any
supplementary information available should be included here]. See
DOI: 10.1039/x0xx00000x
Please do not adjust margins

Please do not adjust margins
Green Chemistry
Page 2 of 5
COMMUNICATION
Journal Name
Table 2 Substrate Scope of boronic acidsa
View Article Online
DOI: 10.1039/C9GC02229E
O2
UV, Et3N
B(OH)2
OH
R
R
2-MeTHF, rt
b
a
OH
R
OH
OH
R
R
b
2b
3b
4b
5b
6b
7b
8b
9b
, R = CH3, 99%
21b
22b
23b
24b
25b
26b
27b
28b
, R = Me, 93%
, R = F, 70%
12b
13b
14b
15b
16b
17b
18b
19b
20b
, R = SCH3, 70%
, R = TMS, 95%
, R = CF3, 84%
, R = CN, 91%
, R = NO2, 91%
, R = CHO, 94%
29b
30b
31b
32b
33b
, R = Me, 63%
t
b
, R = Bu, 86%
, R = OMe, 69%
b
, R = F, 95%
, R = Cl, 85%
, R = Br, 52%
, R = I, 24%
, R = Cl, 67%
, R = CO2CH3, 65%
b
, R = CF3, 96%
, R = NO2, 93%
, R = acetyl, 68%
, R = OMe, 99%
%
, R = Ph, 86
, R = vinyl, 23%
, R =OPh, 73%
, R = acetyl, 73%
b
, R = OCH Ph, 67%
, R = OH, 98%
, R = CO2CH3, 93%
2
b
10b
11b
, R = OMe, 71%
, R = vinyl, 58%
b
, R = OH, 91%
OMe
OH
MeO
MeO
OH
OH
OH
OH
OH
OMe
38b
b
39b
34b
35b
, 80%
, 53%
, 73%
36b
, 55%
OH
37b
, 78%
OH
, 76%
OH
OH
O
O
OH
OH
O
N
b
b
b
43b
41b
, 82%
, 0%
42b
45b
, 50%
, 0%
44b
40b
, 79%
, 88%
OH
S
OH
OH
N
OH
S
N
OH
Ph
b
b
b
b
b
47b
50b
, 85%
46b
, 73%
, 71%
49b
48b
, 71%
, 85%
OH
OH
b
b
51b
52b
, 99%
, 71%
aReaction conditions: a (0.3 mmol), O2 (1 atm), UV lamp (15 W), Et3N (0.45 mmol), 2-MeTHF (4 mL), rt, 24 h, isolated yields. b48 h.
We set out to screen the optimal reaction conditions by The similar result was obtained when the reaction was
selecting [1,1'-biphenyl]-4-ylboronic acid 1a as model performed under air atmosphere (entry 13). The replacement
substrate (Table 1). It was observed that the model reaction of the O2 with the N2 atmosphere shut down this
carried out in DMF under O2 atmosphere at room temperature transformation (entry 14), indicating that oxygen played an
with UV irradiation in the absence of a photocatalyst furnished essential role in the reaction. Further investigation of light
the expected product 1b in 23% yield (entry 1). To our delight, sources showed that visible light also successfully enabled this
the addition of Et3N as an additive resulted in a remarkably transformation in the absence of a photocatalyst, albeit in
increased yield (entry 2). Screening of solvents indicated that relatively lower yields (entries 15-17). Control experiment in
2-MeTHF served as the optimal solvent, affording the desired dark conditions failed to deliver the desired product,
product in 92% yield (entries 3-9). Switching the Et3N to other confirming the necessity of continuous UV irradiation (entry
n
additives such as DIPEA, (Me)2EtN or (Me)2 BuN gave the 18). Therefore, the reaction conditions of entry 9 proved to be
expected products in relatively lower yields (entries 10-12). optimal.
2 | J. Name., 2012, 00, 1-3
This journal is © The Royal Society of Chemistry 20xx
Please do not adjust margins

Please do not adjust margins
Page 3 of 5
Green Chemistry
Journal Name
With the optimized reaction conditions in hand, we next
COMMUNICATION
To shed light on the mechanism of this photochemical
View Article Online
investigated the substrate scope of boronic acids including hydroxylation of boronic acids, someDOcoI:n1t0r.1o0l39e/Cxp9GerCi0m2e22n9tEs
arylboronic acids and alkylboronic acids (Table 2). Arylboronic were conducted (Scheme 1). First, The model reaction
acids containing various functional groups on the aromatic ring performed under 18O2 atmosphere successfully offered the
have proved to be compatible in the standard conditions and 18O-labeled product (Scheme 1a), demonstrating the oxygen
afforded hydroxylated products (2b-50b). Arylboronic acids atom of the phenol product was derived from O2. Then we
bearing various substitutions at the para-position of the intended to exam the effect of photocatalysts on the reaction
aromatic ring ranging from electron-donating groups such as efficiency. Surprisingly, it was found that the presence of
alkyl (2a and 3a), alkoxy (8a-10a), methylthio (12a) and TMS photocatalysts such as RuCl2(bpy)3.6H2O, Zinc phthalocyanine
(13a) to electron-withdrawing groups such as halogens (4a- and methylene blue trihydrate did not facilitate this reaction
7a), trifluoromethyl (14a), nitro (16a), acetyl (18a) and ester but slightly descreased the reaction efficiency (Figure S2, see
(19a), reacted well to provide the desired products under the the supporting information). On basis of these results and
standard conditions. Among these, the resulting products previous references,16 it could be inferred that the amines may
bearing halogens such as Cl, Br and I could be further utilized promote the generation of superoxide radical anion (O2•−).
for the synthesis of more complex organic compounds. It is Inspired by previous work17 which demonstrated that p-cresol
worth noting that these sensitive groups including phenolic was an efficient superoxide generator, we reckoned that in
hydroxyl (11a), aldehyde (17a) and vinyl (20a) groups were situ generated phenols also could contribute as a catalyst to
also amenable to the reaction conditions, offering the desired the generation of O2•−. This inference was supported by the
product in 91%, 94% and 58% yields respectively. Thus, it can fact that the replacement of Et3N with 2,6-dimethyl phenol led
be inferred from these results that electronic properties of to excellent reaction efficiency (Figure S3, see the supporting
substitution had little effect on reaction efficiency. In addition, information). The O2•− intermediate was detected by nitro-blue
the optimized reaction conditions were compatible with a tetrazolium (NBT),18 judged from the color change of the
range of substitutions at the ortho and meta-positions of the reaction solution from light brown to deep purple during the
•−
aromatic ring (21a-33a). These observations revealed that the reaction (Figure 1). Additionally, the existence of O2
substitutions at the meta and para-positions led to higher intermediate was further confirmed by the control experiment
yields compared with that at the ortho-position. Hindered 2,6- in which PhB(OH)2 reacted with in situ generated NaO2 under
substituted arylboronic acids have proved to be suitable dark condition (Scheme 1b).19 When triethylamine was
substrates (35a-38a). The substrates with multiple strong replaced by N,N-dicyclohexylmethylamine, the co-proyduct
electron-donating groups was successfully converted to the dicyclohexylamine was detected by GC-MS (Scheme 1c).
NBT(0.3 equiv)
Et3N (1.5 equiv)
desired products in good yields (38b-40b). Unfortunately,
B(OH)2
OH
heterocyclic boronic acids were ineffective under the standard
reaction conditions to provide the desired products (41b and
42b). The substrates bearing a fused ring smoothly underwent
the photocatalyst-free aerobic hydroxylation, affording the
corresponding products with 50%-85% yields (43b-49b). In the
case of (9,9-dimethyl-9H-fluoren-2-yl)boronic acid, the
reaction delivered the product 50b in 85% yield. Remarkably,
the scope could be expanded to alkylboronic acids under the
standard reaction conditions, providing the desired products in
71% and 99% yields respectively (51b and 52 b).
UV (15 W), O2 (1 atm)
2-MeTHF (4 mL), rt, 24 h
Me
Me
2a
2b
Figure 1. The color change of the reaction solution during the
18O2 (1 atm)
reaction in the presence of NBT.
UV, Et3N (1.5 equiv)
18OH
1a
(a)
(b)
2-MeTHF (4 mL), rt, 24 h
According to these results and relevant literature,14, 15c, 15f
a
O18
-
, 90% yield
1b
possible mechanism for the photocatalytic oxidative
hydroxylation of boronic acids is described in Scheme 2. At the
beginning, Et3N can serve as photosensitizer and afford singlet
oxygen (1O2) under UV irradiation. Next, the O2 obtains an
electron from Et3N (or phenols), producing a O2 along with a
radical cation (Et3N•+). The resulting O2•− can add to the vacant
porbital of boron to afford intermediate A which undergoes
single electron transfer (SET) with Et3N•+ to give intermediate
B, while Et3N•+ is converted into Et2NH. Next, intermediate B
undergoes 1,2-aryl shift, followed by hydrolysis to provide the
final product.
distilled water, N2
2a
NaO2
NaOH
H2O2
2b
rt, 10 min, dark
2-MeTHF, N2
rt, 24 h, dark
96% yield
1
•−
N,N-dicyclohexylmethylamine
(1.5 equiv)
UV, O2
(c)
1a
1b
91% yield
N
H
2-MeTHF (4 mL), rt, 24 h
detected by GC-MS
Scheme 1. Some control experiments.
This journal is © The Royal Society of Chemistry 20xx
J. Name., 2013, 00, 1-3 | 3
Please do not adjust margins

Please do not adjust margins
Green Chemistry
Page 4 of 5
COMMUNICATION
Journal Name
SET
Et3N
UV
2009, 48, 8725; (f) L. Yang, Z. Huang, G. Li, W. Zhang, R. Cao,
1O2
C. Wang, J. Xiao and D. Xue, Angew. Chem., Int. VEiedw.,A2rt0ic1le8O,n5lin7e,
O2
O2
Et3N
DOI: 10.1039/C9GC02229E
1968.
(or phenols)
3
(a) J. Zheng, S. Lin, X. Zhu, B. Jiang, Z. Yang and Z. Pan, Chem.
Commun., 2012, 48, 6235; (b) L. Wang, W. Zhang, D. Sheng
Su, X. Meng and F.-S. Xiao, Chem. Commun., 2012, 48, 5476;
(c) T. Begum, A. Gogoi, P. K. Gogoi and U. Bora, Tetrahedron
Lett., 2015, 56, 95; (d) A. D. Chowdhury, S. M. Mobin, S.
Mukherjee, S. Bhaduri and G. K. Lahiri, Eur. J. Inorg. Chem.,
2011, 2011, 3232; (e) H. Yang, Y. Li, M. Jiang, J. Wang and H.
Fu, Chem. - Eur. J., 2011, 17, 5652; (f) J. Xu, X. Wang, C. Shao,
D. Su, G. Cheng and Y. Hu, Org. Lett., 2010, 12, 1964; (g) K.
Inamoto, K. Nozawa, M. Yonemoto and Y. Kondo, Chem.
Commun., 2011, 47, 11775; (h) N. Gogoi, P. K. Gogoi, G.
Borah and U. Bora, Tetrahedron Lett., 2016, 57, 4050.
(a) A. Gogoi and U. Bora, Tetrahedron Lett., 2013, 54, 1821;
(b) S. Gupta, P. Chaudhary, V. Srivastava and J. Kandasamy,
Tetrahedron Lett., 2016, 57, 2506.
RB(OH)2
Et2NH
OH
OH
Et3N
O
O
B
O
B
OH
OH
SET
R
R
OH
B
A
Migration
-OH
OH
B(OH)3
O
R
OH
B
R
hydrolysis
OH
C
4
5
Scheme 2. A plausible mechanism
N. Chatterjee and A. Goswami, Tetrahedron Lett., 2015, 56,
1524.
6
7
8
9
G. Cheng, X. Zeng and X. Cui, Synthesis, 2014, 46, 295.
D.-S. Chen and J.-M. Huang, Synlett, 2013, 24, 499.
S. Guo, L. Lu and H. Cai, Synlett, 2013, 24, 1712.
G. W. Kabalka, T. M. Shoup and N. M. Goudgaon,
Tetrahedron Lett., 1989, 30, 1483.
Conclusions
In conclusion, we have disclosed a the photocatalytic aerobic
hydroxylation of boronic acids using O2 as the oxidant,
providing a green entry to a variety of functionalized phenols
and aliphatic alcohols in a highly concise fashion. This new
protocol features photocatalyst-free conditions, wide
substrate scope and excellent functional group compatibility.
In particular, the advantages including the mild reaction
conditions and good functional group tolerance enabled late
stage modification of complex molecules. Furthermore, the
photocatalyst-free and metal-free conditions wouldn’t only
significantly decrease the costs, but also allow for easy
separation of products, thus offering the approach an
opportunity to find some applications in synthetic chemistry.
10 (a) G. A. Molander and L. N. J. Cavalcanti, J. Org. Chem.,
2011, 76, 623; (b) J. J. Molloy, T. A. Clohessy, C. Irving, N. A.
Anderson, G. C. Lloyd-Jones and A. J. B. Watson, Chem. Sci.,
2017, 8, 1551.
11 C. Zhu, R. Wang and J. R. Falck, Org. Lett., 2012, 14, 3494.
12 (a) K. Hosoi, Y. Kuriyama, S. Inagi and T. Fuchigami, Chem.
Commun., 2010, 46, 1284; (b) H.-L. Qi, D.-S. Chen, J.-S. Ye
and J.-M. Huang, J. Org. Chem., 2013, 78, 7482; (c) H. Jiang,
L. Lykke, S. U. Pedersen, W.-J. Xiao and K. A. Jørgensen,
Chem. Commun., 2012, 48, 7203.
13 (a) J. Twilton, C. C. Le, P. Zhang, M. H. Shaw, R. W. Evans and
D. W. C. MacMillan, Nat. Rev., 2017, 1, 0052; (b) K. L. Skubi,
T. R. Blum and T. P. Yoon, Chem. Rev., 2016, 116, 10035.
14 Y.-Q. Zou, J.-R. Chen, X.-P. Liu, L.-Q. Lu, R. L. Davis, K. A.
Jørgensen and W.-J. Xiao, Angew. Chem., Int. Ed., 2012, 51,
784.
Conflicts of interest
15 (a) T. Toyao, N. Ueno, K. Miyahara, Y. Matsui, T.-H. Kim, Y.
Horiuchi, H. Ikeda and M. Matsuoka, Chem. Commun., 2015,
51, 16103; (b) X. Yu and S. M. Cohen, Chem. Commun., 2015,
51, 9880; (c) J. A. Johnson, J. Luo, X. Zhang, Y.-S. Chen, M. D.
Morton, E. Echeverría, F. E. Torres and J. Zhang, ACS Catal.,
2015, 5, 5283; (d) A. K. Simlandy, B. Bhattacharyya, A.
Pandey and S. Mukherjee, ACS Catal., 2018, 8, 5206; (e) H.-P.
Liang, Q. Chen and B.-H. Han, ACS Catal., 2018, 8, 5313; (f) S.
P. Pitre, C. D. McTiernan, H. Ismaili and J. C. Scaiano, J. Am.
Chem. Soc., 2013, 135, 13286; (g) H.-Y. Xie, L.-S. Han, S.
Huang, X. Lei, Y. Cheng, W. Zhao, H. Sun, X. Wen and Q.-L.
Xu, J. Org. Chem., 2017, 82, 5236; (h) I. Kumar, R. Sharma, R.
Kumar, R. Kumar and U. Sharma, Adv. Synth. Catal., 2018,
360, 2013; (i) D.-P. Luo, Y.-F. Huang, X.-Y. Hong, D. Chen, G.-
X. Li, X.-B. Huang, W.-X. Gao, M.-C. Liu, Y.-B. Zhou and H.-Y.
Wu, Adv. Synth. Catal., 2019, 361, 961.
16 C. Ferroud, P. Rool and J. Santamaria, Tetrahedron Lett.,
1998, 39, 9423.
17 W. M. Draper and D. G. Crosby, J. Agric. Food Chem., 1983,
31, 734.
18 (a) M. Hayyan, M. A. Hashim and I. M. AlNashef, Chem. Rev.,
2016, 116, 3029; (b) H. Wohlgemuth, K. Mittelstrass, S.
schieschan, J. Bender, H.-J. Weigel, K. Overmyer, J.
Kangasjärvi, H.J. andermann and C. Langebartels, Plant, Cell
& Environment, 2002, 25, 717.
19 U. Stoin, A.r I. Shames, I. Malka, I. Bar and Y. Sasson,
ChemPhysChem, 2013, 14, 4158.
There are no conflicts to declare.
Acknowledgements
We are grateful for financial support from the National Natural
Science Foundation of China (21472140 and 21372177), the
Wenzhou Science
& Technology Bureau Program (No.
G20170021) and Xinmiao Talent Planning Foundation of
Zhejiang Province (No. 2018R429058).
Notes and references
1
(a) S. Quideau, D. Deffieux, C. Douat-Casassus and L.
Pouységu, Angew. Chem., Int. Ed., 2011, 50, 586; (b) Z.
Rappoport, The Chemistry of Phenols; Wiley-VCH: Weinheim,
2003.
(a) K. W. Anderson, T. Ikawa, R. E. Tundel and S. L. Buchwald,
J. Am. Chem. Soc., 2006, 128, 10694; (b) T. Schulz, C.
Torborg, B. Schäffner, J. Huang, A. Zapf, R. Kadyrov, A.
Börner and M. Beller, Angew. Chem., Int. Ed., 2009, 48, 918;
(c) J. W. Han, J. Jung, Y.-M. Lee, W. Nam and S. Fukuzumi,
Chem. Sci., 2017, 8, 7119; (d) G. Shan, X. Yang, L. Ma and Y.
Rao, Angew. Chem., Int. Ed., 2012, 51, 13070; (e) A. Tlili, N.
Xia, F. Monnier and M. Taillefer, Angew. Chem., Int. Ed.,
2
4 | J. Name., 2012, 00, 1-3
This journal is © The Royal Society of Chemistry 20xx
Please do not adjust margins

Page 5 of 5
Green Chemistry
View Article Online
DOI: 10.1039/C9GC02229E
O2 (1 atm)
UV (15 W), Et3N
B(OH)2
OH
R
R
2-MeTHF, rt
R = Aryl, alkyl
metal-free and photocatalyst-free
mild conditions
wide substrate scope
excellent functional group compatibility
We disclose a photoinduced aerobic hydroxylation of boronic acids under photocatalyst-free
conditions, providing a green entry to phenols and alcohols.