10.1002/adsc.202000216
Advanced Synthesis & Catalysis
Research (B) (19H02728 to E.S.). We thank Professor Manabu
Abe (Hiroshima University) for assistance in DFT calculations.
radical I (step a), which adds to the aromatic ring of
chloroarene 2 (step b). Cl• departs from the resulting
cyclohexadienyl radical (II) to give -arylation
product 3 (step c). The eliminated Cl• undergoes H-
abstraction to regenerate -hydroxyalkyl radical I
(step d). From the results that even a weak base such
as KOAc is sufficiently effective (cf. Table 1, entries
1 and 2) and that strong bases such as K2CO3 and
Cs2CO3, which can form the corresponding metal
alkoxides, induce side reactions (cf. Table 1, entries 7
and 8), the role of a base is not likely to form a metal
alkoxide to facilitate abstraction of -hydrogen. It is
also unlikely that a base simply works to neutralize
References
[1] For examples of the transition metal-mediated
reaction: a) C. A. Correia, L. Yang, C.-J. Li, Org. Lett.
2011, 13, 4581–4583; b) C. Berini, O. Navarro, Chem.
Commun. 2012, 48, 1538–1540; c) S. Wang, S. Xing,
Y. Zhang, Y. Fan, H. Zhao, J. Wang, S. Zhang, W.
Wang, RSC Adv. 2019, 9, 41847–41850. For the
photoredox-catalyzed reaction: d) C. A. Huff, R. D.
Cohen, K. D. Dykstra, E. Streckfuss, D. A. DiRocco,
S. W. Krska, J. Org. Chem. 2016, 81, 6980–6987. For
the light-induced reaction: e) L. Niu, J. Liu, X.-A.
Liang, S. Wang, A. Lei, Nat. Commun. 2019, 10, 467.
For a review: f) S.-R. Guo, P. S. Kumar, M. Yang,
Adv. Synth. Catal. 2017, 359, 2–25.
R3
Cl
R1
R2
OH
R3
2
•
1/2 t-BuOOt-Bu
t-BuO•
Cl
step b
II
[2] For early examples, see: a) M. H. Palmer, P. S.
McIntyre, Tetrahedron Lett. 1968, 9, 2147–2150; b)
W. Buratti, G. P. Gardini, F. Minisci, F. Bertini, R.
Galli, M. Perchinunno, Tetrahedron 1971, 27, 3655–
3668. For reviews, see: c) F. Minisci, Synthesis 1973,
1–24; d) F. Minisci, E. Vismara, F. Fontana,
Heterocycles 1989, 28, 489–519. For recent advances
in the Minisci-type reaction, see refs 1d and 1e as
well as the following review: e) R. S. J. Proctor, R. J.
Phipps, Angew. Chem. Int. Ed. 2019, 58, 13666–
13699; Angew. Chem. 2019, 131, 13802–13837.
HO
R1
HO
R1
step a
•
H
R2
R2
t-BuOH
1
I
step c
step d
base•HCl
HCl
R3
Cl•
HO
R1
base
HO
R2
H
R1
3
R2
1
Scheme 3. A Plausible Mechanism.
[3] For examples of benzothiazoles: a) T. He, L. Yu, L.
Zhang, L. Wang, M. Wang, Org. Lett. 2011, 13,
5016–5019; b) W.-X. Xu, X.-Q. Dai, J.-Q. Weng,
ACS Omega 2019, 4, 11285–11292. For thiophenes
having an electron-withdrawing group: c) E.
Kianmehr, M. Fardpour, K. M. Khan, Eur. J. Org.
Chem. 2017, 2661–2668.
HCl generated in step d as the type of bases
sensitively affects the efficiency.
In conclusion, we have developed a simple
protocol for the direct -arylation of alcohols using
aryl chlorides and a substoichiometric amount of t-
BuOOt-Bu respectively as arylation reagents and a
radical initiator, where a radical chain involving a
homolytic aromatic substitution mechanism is
operative.
[4] a) A. Lipp, G. Lahm, T. Opatz, J. Org. Chem. 2016,
81, 4890–4897; b) A. M. Nauth, A. Lipp, B. Lipp, T.
Opatz, Eur. J. Org. Chem. 2017, 2099–2103.
[5] J. Twilton, M. Christensen, D. A. DiRocco, R. T.
Ruck, I. W. Davies, D. W. C. MacMillan, Angew.
Chem. Int. Ed. 2018, 57, 5369–5373; Angew. Chem.
2018, 130, 5467–5471.
Experimental Section
-Arylation of Alcohols with Aryl Chlorides (Tables 1,
2 and 3): Representative Procedure (Table 1, Entry
3).[9]
[6] a) Y. Ikeda, R. Ueno, Y. Akai, E. Shirakawa, Chem.
Commun. 2018, 54, 10471–10474. For the -
arylation of alkylamines with aryl halides using a
To a 4 mL vial equipped with a stir bar in a glove box were
added successively 2-propanol (1a: 902 mg, 15.0 mmol),
2-chlorobenzothiazole (2a: 84.8 mg, 0.500 mmol), t-
BuOOt-Bu (14.6 mg, 0.100 mmol), NaHCO3 (42.0 mg,
0.500 mmol). The vial was taken out of the glove box and
the mixture was stirred for 24 h at 120 °C. The resulting
mixture was poured into water (10 mL), extracted with
ethyl acetate (15 mL × 3), washed with brine (5 mL), and
dried over Na2SO4. After filtration and concentration, the
crude mixture was subjected to silica gel chromatography
(CHCl3/MeOH = 15/1) to give the corresponding product
(3aa: 94.7 mg, 98% yield).
stoichiometric amount of
a tert-butoxy radical
precursor, see: b) R. Ueno, Y. Ikeda, E. Shirakawa,
Eur. J. Org. Chem. 2017, 4188–4193.
[7] The stability of radical species is evaluated by bond
dissociation energy (BDE). According to DFT
calculations using B3LYP/6-31+G(d,p), BDE values
(kcal/mol) of the O–H bond in PhS(=O)O–H, the -
C–H bond in ethanol and H–Cl are 81, 93 and 100,
respectively, showing that benzenesulfonyl radical is
much more stable than -hydroxyethyl radical and
Cl•. The experimental BDE values of the latter two
are available (96 and 103, respectively) in the
literature and are almost the same as the calculated
Acknowledgements
This work has been supported financially in part by Grant-in-
Aids for Scientific Research (B) (16H04151 to E.S.) and Scientific
4
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