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Cite This: J. Am. Chem. Soc. 2019, 141, 9124−9128
Visible-Light-Induced Organocatalytic Borylation of Aryl Chlorides Li Zhang and Lei Jiao* Center of Basic Molecular Science, Department of Chemistry, Tsinghua University, Beijing 10084, China
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S Supporting Information *
of unactivated chloroarenes as substrates in transition-metal-free borylation reactions remains a major challenge. 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 UVirradiation, and most recently, Schelter14 realized a photoinduced borylation of aryl chlorides in the presence of a rareearth 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 an 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 a 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 that17b 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 an 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. 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
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.
A
rylboronates 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 a broad substrate scope and good functional group compatibility (Scheme 1a). More recently, transition-metal-free Scheme 1. Borylation of Aryl Chlorides
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 © 2019 American Chemical Society
Received: January 25, 2019 Published: May 29, 2019 9124
DOI: 10.1021/jacs.9b00917 J. Am. Chem. Soc. 2019, 141, 9124−9128
Communication
Journal of the American Chemical Society
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 TCSPC. (C) Stern−Volmer plot of the luminance quenching experiment with 1,4-dichlorobenzene (1,4DCB).
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 SI 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). The above experimental findings served as a proof-of-concept of the visible-light-induced electron transfer of SED complex 2, which enabled the activation and functionalization of chloroarenes via a radical pathway. In this line, we hope to develop a synthetically useful borylation reaction of chloroarenes utilizing this reaction mode. Therefore, we optimized the reaction conditions for the borylation of chloroarene 4a using a mixture of B2pin2, methoxide, and pyridine 1 to generate complex 2 in situ under visible-light irradiation (Table 1). Here only a catalytic amount of 1 was used, since 1 could be regenerated after SET and thus acts as an organocatalyst.17b It was found that the optimal reaction conditions include the use of a 10 W 400 nm LED as the light source, MeCN as the solvent, and performing the reaction at room temperature. MeOK and MeONa as the methoxide source resulted in similar yields of the desired borylation product 5a (entries 1 and 2), thus the inexpensive MeONa was employed in the synthetic reactions. Other solvents, such as MTBE, DMSO, and DMAc, were proved inferior (entries 3−5). Both UV (365 nm) and blue light (450 nm) could promote the reaction, albeit with decreased yields (entries 6 and 7). The use of 254 nm irradiation (low-pressure Hg lamp) led to a dramatically decreased conversion (entry 8), probably due to various species exhibiting intense absorption within this region, which interfere with the efficient excitation of complex 2. Control experiments revealed the essential role of both photoirradiation and pyridine 1 on the observed reactivity (entries 9 and 10). Of special note, the reaction afforded a similarly good yield when set up under air (entry 11), which renders this method rather practical, because it avoids the rigorous deoxygenation procedure. When bis(hexylene
Figure 1. Study on the reactivity of diboron-derived SEDs. (A) The formation of SEDs from diboron, methoxide, and 4-phenylpyridine (1). (B) The UV−vis 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.
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 4-chloroanisole 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; and when a 400 nm LED was used (to excite complex 2), both bromo- and 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 ). In order to figure out how the excited state of SED reacts with chloroarenes, we performed fluorescence lifetime measurement and luminance quenching experiments 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 9125
DOI: 10.1021/jacs.9b00917 J. Am. Chem. Soc. 2019, 141, 9124−9128
Communication
Journal of the American Chemical Society Table 1. Optimization of Reaction Conditionsa
Table 2. Borylation of Aryl Chlorides
entry
change from standard condtions
conv. (%)b
yield (%)b
1 2 3 4 5 6 7 8
none MeOK instead of MeONa MTBE instead of CH3CN DMSO instead of CH3CN DMAc instead of CH3CN 365 nm LED instead of 400 nm LED 450 nm LED instead of 400 nm LED 254 nm Hg lamp (28 W) instead of 400 nm LEDd without light without 4-phenylpyridine (1) reaction set up under aire B2hex2f instead of B2pin2 complex 2·DME (10 mol%) instead of 1
99 96 33 91 99 40 66 6
92 (89)c 89 26 42 52 35 53 5
