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Visible-Light-Induced Organocatalytic Borylation of Aryl Chlorides Li Zhang, and Lei Jiao J. Am. Chem. Soc., Just Accepted Manuscript • DOI: 10.1021/jacs.9b00917 • Publication Date (Web): 29 May 2019 Downloaded from http://pubs.acs.org on May 29, 2019
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Journal of the American Chemical Society
Visible-Light-Induced Chlorides
Organocatalytic
Borylation
of
Aryl
Li Zhang and Lei Jiao* Center of Basic Molecular Science (CBMS), Department of Chemistry, Tsinghua University, Beijing 10084, China
Supporting Information Placeholder ABSTRACT: The preparation of arylboronates from unactivated aryl chlorides in a transition-metal-free manner is rather challenging. There are only few examples to achieve this goal by using ultraviolet irradiation. Based on the mechanistic understanding of the diboron/methoxide/pyridine reaction system, we achieved photoactivation of the in situ generated super electron donor, and developed a visible-light-induced organocatalytic method for efficient borylation of unactivated aryl chlorides.
Arylboronates are widely utilized in organic synthesis, materials science, and drug discovery as key building blocks.1-2 There is a constant quest for efficient synthetic methods to access arylboronates from simple and readily available starting materials.3-5 Haloarenes are most commonly employed precursors to arylboronates. Over the past decades, transition metal catalysis (e.g., Pd, Cu, Ni, Co,3 and Zn4) enabled an efficient approach to arylboronates employing iodo-, bromo-, and more challenging chloroarenes as substrates, which featured broad substrate scope and good functional group compatibility (Scheme 1a). More recently, transition-metal-free borylation methods,6-12 in particular photochemical borylation reactions,8-9,10f-g,11b-d,13-14 have attracted great research interests and opened a new avenue to arylboronates. However, most of these methods exhibit limited reactivities compared with transition-metal-catalyzed reactions, which often require the use of more reactive aryl iodides and bromides as substrates. The use of unactivated chloroarenes as substrates in transition-metal-free borylation reactions remains a major challenge.
photoinduced borylation of aryl chlorides in the presence of a rare-earth metal photocatalyst, CeCl63− (Scheme 1b). Despite these achievements, more efficient solutions to chloroarene borylation are still in a high demand, and it would be valuable to develop a new mode for chloroarene borylation avoiding the use of expensive quartz reactor and rare-earth metal photocatalyst. Herein, we report an efficient visible-light-induced organocatalytic borylation reaction of aryl chlorides developed based on mechanistic study, which features broad substrate scope and operational convenience (Scheme 1c). Recently, we have developed a radical borylation reaction of aryl iodides and bromides employing diboron(4) as the boron source and 4-phenylpyridine (1) as the catalyst.17a Further mechanistic study showed that,17b the reaction between B2pin2 and pyridine 1 in the presence of base produces a mixture of super electron donors (SEDs) consisting of complexes 2 and 3 (Figure 1A). The SED mixture activates haloarenes via single electron transfer (SET) to form aryl radical as a key intermediate, which undergoes borylation with the diboron(4) compound. With this mechanistic information in mind, we hoped to realize the activation of chloroarenes utilizing the B2pin2/methoxide/pyridine reaction system by studying the substituent effect of the SEDs. However, attempts to improve the reduction ability of the SED mixture by tuning the electronic nature of the substituents on pyridine 1 proved unsuccessful.
Considering the nature of aryl chlorides [e.g., for PhCl, Ered(PhCl/PhCl•-) = -3.28 V vs Fc+/0;15 BDE(C-Cl) = 97.1 kcal/mol16], the cleavage of the C—Cl bond in a transitionmetal-free manner is rather difficult. As a breakthrough, Li8a,d and Larionov8b,c independently reported the borylation of aryl chlorides with a diboron(4) reagent under 254 nm UV-irradiation; and most recently, Schelter14 realized a
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Scheme 1. Borylation of Aryl Chlorides
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H
B2pin2
(a) Transition-metal-catalyzed borylation of aryl halides: Ar
X
X = I, Br, Cl
Various transition-metal catalyst
+
Ar
HB(OR)2 or B2(OR)4
Ar
Cl
B2(OR)4 (ref. 8)
or
N
cat. CeCl63UV light (365 nm) glass reactor B2(OR)4 (ref. 14)
Ar
+
2
1
(b) Photoinduced borylation of aryl chlorides: Catalyst free UV light (254 nm) quartz reactor
K
THF, rt, 2 h
+ Ph
H N B O O
N
18-C-6
MeOK
OR (refs. 3-4) B OR
Ph
Ph
Ph
(A)
N Me O B O O K 3
Mixture of super electron donors (SEDs)
OR B OR
(c) Transition-metal-free borylation of aryl chlorides under visible light (this work):
Ar
Cl
cat. 4-PhPy (1) visible light (400 nm) glass reactor base, B2(OR)4
Ar
OR B OR
Inspired by the principle that photoexcitation of an electron donor (or acceptor) could enhance its reduction (or oxidation) ability significantly,18-20 we intended to investigate the photochemical properties of these SED complexes, which remains unexplored and may lead to a solution for chloroarene activation. The UV-vis spectrum showed that ate complex 2 has an absorption band in the 300-500 nm region, while radical anion complex 3 exhibits a characteristic absorption band in the 500-600 nm region (Figure 1B). Fluorescence spectroscopic study revealed that the emission maximums of complexes 2 and 3 are at 547 and 621 nm, respectively. The observed absorption allows for visible-light photoactivation of these SED complexes, and the redox potentials of their excited states should be significantly decreased as estimated by the Rehm-Weller formalism21 (e.g., Eox(2•+/2) = -1.11 V and Eox*(2•+/2*) = 3.87 V vs Fc+/0). In principle, the SED mixture, after photoexcitation, is able to undergo SET with more difficult substrates, such as chloroarenes. Gratifyingly, this proposal was proved feasible by a series of control experiments (Figure 1C): without photoirradiation, the SED mixture was able to slowly reduce 4-bromoanisole but not 4chloroanisole at room temperature; when a 520 nm LED was applied as the light source (to excite complex 3), the reduction of 4-bromoanisole took place more efficiently and the reduction of 4-chloroanisole became observable; when a 400 nm LED was used (to excite complex 2), both bromoand chloroarenes could be reduced efficiently. These observations indicated that, the reduction abilities of both complexes have indeed been enhanced after photoexcitation, and complex 2 exhibits a superior reactivity. A further experiment with independently prepared complex 2·DME under 400 nm photoirradiation emphasized the important role of complex 2 in the activation of chloroarene by photoinduced SET (Figure 1D). The reduction of 4chloroanisole to anisole was confirmed to proceed via the aryl radical intermediate, since the reaction performed in THF-d8 as the solvent resulted in significant deuterium incorporation in the 4-position of the anisole product (see the Supporting Information).
Ph
(D)
Ph H
MeO
Cl +
4a (2 equiv.)
O
K O
H N B O O
N
400 nm LED (10 W) THF, rt, 3 h = 9.3% (@ 24% conversion)
MeO
H
82% yield (GC)
2·DME (1 equiv.)
Figure 1. Study on the reactivity of diboron-derived super electron donors (SEDs). (A) The formation of SEDs from diboron, methoxide, and 4-phenylpyridine (1); (B) The UVvis spectra of pure ate complex 2 and the SED mixture of complexes 2 and 3; (C) Reactivity of the SED mixture for haloarene activation under photoexcitation; (D) Photoinduced activation of chloroarene by ate complex 2. In order to figure out how the excited state of SED reacts with chloroarenes, we performed fluorescence lifetime measurement and luminance quenching experiment of ate complex 2. The time-correlated single photon counting (TCSPC) experiment showed that complex 2 has a fluorescence lifetime (τ) of 6.1 ± 0.2 ns (Figure 2B). The luminance quenching experiment with 1,4-dichlorobenzene (4w) as the quencher revealed a linear relationship defined by the Stern-Volmer equation, with a Stern-Volmer constant, Ksv, of 8.6 M-1 (Figure 2C). Thus the quenching rate coefficient (kq) between the singlet excited state (S1) of 2 and chloroarene 4w was calculated to be 1.4 ×109 M-1·s-1, indicating a diffusion-controlled process. Given that the formation of a donor-acceptor complex between 2 and the chloroarene has not been observed, and the possibility of the triplet excited state (T1) of 2 participating in the SET process has been excluded (see the Supporting Information for details), it is most likely that the S1 state of 2 is the reactive species that undergoes SET with the chloroarene substrate (Figure 2A).
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Complex 2 (Ground state)
Eox(2•+ /2) = -1.11 V
hv
Eox*(2•+ /2*) = -3.87 V Fluorescence emission (max 547 nm)
Quench of 2* by chloroarene via SET
(400 nm)
Complex 2* (Singlet excited state)
ArCl
Table 2. Borylation of Aryl Chlorides
Ar
[ArCl]
SET
borylation reaction of chloroarenes utilizing this reaction m o d e . T h e r e f o r e
Ar
Cl
cat. 4-PhPy (1)
Cl + B2pin2
Ar
MeONa, CH3CN 400 nm LED, rt, 12 h
4
Bpin 5
MeO MeO
CH3
Bpin 5a (89%)
Bpin
Bpin 5b (83%) (80%b for 1.88 g scale)
H 3C
Bpin 5d (90%) (68%b for 1.37 g scale)
H 3C Bpin H3C
Bpin
Bpin
5e (92%)
Figure 2. Reaction of excited state ate complex with aryl chloride. (A) Proposed reaction mechanism; (B) Determination of the fluorescence lifetime of complex 2 by time-correlated single photon counting (TCSPC); (C) SternVolmer plot of the luminance quenching experiment with 1,4-dichlorobenzene (1,4-DCB).
5c (90%)
t
Bpin
Bu
H3C 5g (88%)
5f (90%)
5h (86%)
Me N
Bpin
O
F
Bpin
Bpin
AcHN
Bpin
Me 5j (40%)
5i (74%) O
O Bpin
Bpin
Bpin
MeO
EtO
NC
5n (82%c)
5m (90%)
5l (72%)
5k (85%) (78%b for 1.73 g scale) NC
5o (80%)
Bpin 5p (80%)
Bpin
Table 1. Optimization of Reaction Conditionsa
N Bpin Bpin
Ph MeO
Cl + B2pin2 4a
Entry 1
5q (80%)
N (1)
OR
MeONa, CH3CN 400 nm LED, rt, Ar, 12 h
Change from standard condtions
MeO
Conv. (%)b
Yield (%)b
99
92 (89)c
None
pinB
OR 5a/5a'
2
MeOK instead of MeONa
96
89
3
MTBE instead of CH3CN
33
26
4
DMSO instead of CH3CN
91
42
5
DMAc instead of CH3CN
99
52
6
365 nm LED instead of 400 nm LED
40
35
7
450 nm LED instead of 400 nm LED
66
53
8
254 nm Hg lamp (28 W) instead of 400 nm LEDd
6
5
9
Without light
