Silylboronate-Mediated Defluorosilylation of Aryl Fluorides with or without Ni-Catalyst

The defluorosilylation of aryl fluorides to access aryl silanes was achieved under transition-metal-free conditions via an inert C–F bond activation. The defluorosilylation, mediated by silylboronates and KOtBu, proceeded smoothly at room temperature to afford various aryl silanes in good yields. Although a comparative experiment indicated that Ni catalyst facilitated this transformation more efficiently, the transition-metal-free protocol is advantageous from a green chemistry perspective.

In 2018, we reported a significant achievement on the C-F bond cleavage of aryl fluorides via defluorosilylation using silylboronates (R 3 SiBPin) in the presence of potassium tert-butoxide (KOtBu) and a catalytic amount of Ni. The C-F bond cleavage occurred via the five-centered transition state via a π-nickel complex and a non-classical oxidative pathway (Scheme 1A); (Cui et al., 2018). Notably, we also found that the C-F bond activation did not require an Ni catalyst in the case of alkyl fluorides. The defluorosilylation of alkyl fluorides proceeded smoothly with R 3 SiBPin exclusively in the presence of KOtBu. A highly nucleophilic, silyl anionic species directly reacts with alkyl fluorides via a concerted S N 2 process (Scheme 1B). The defluorosilylation reaction was then successfully reported by several groups (Gao et al., 2019;Kojima et al., 2019;Mallick et al., 2019;Coates et al., 2019;Lim et al., 2020;Sheldon et al., 2020). In 2019, Martin and co-workers reported the lithiumpromoted defluorosilylation of organic fluorides, in which lithium bis(trimethylsilyl)amide (LiHMDS) and dimethyl ether (DME) cooperated well to activate the inert C-F bond (Scheme 1C); . In the same year, Uchiyama and coworkers also reported a transition-metal-free defluorosilylation of fluoroarenes using PhMe 2 SiBPin and sodium tert-butoxide (NaOtBu) (Kojima et al., 2019). In situ generated silyl anion species enabled the direct defluorosilylation of fluoroarenes (Scheme 1D). In 2021, we have continuously reported the catalyst-free carbosilylation of alkenes using R 3 SiBPin and organic fluorides, including aryl and alkyl fluorides, via selective C-F bond activation (Zhou et al., 2021). The substrate-scope showed slightly better yields when the reaction was performed in the presence of an Ni-catalyst, although we noticed that the effect of Ni-catalyst was not significant (Scheme 1E). While the results of Uchiyama and co-workers (Scheme 1D); (Kojima et al., 2019) and our recent results (Scheme 1E); (Zhou et al., 2021) indicate that Ni-catalyst is not necessary for their transformations, the conditions are not precisely the same such as bases, solvents and reaction times, which is difficult to conclude the Ni-effect. We thus decided to carefully re-examine our original work of defluorosilylation of aryl fluorides in 2018 (Scheme 1A); (Cui et al., 2018) by the same conditions, R 3 SiBPin in the presence of KOtBu, with or without an Ni-catalyst. We disclose herein the improved-catalyst-free conditions for silylboronate-mediated defluorosilylation of aryl fluorides. A wide variety of aryl fluorides 1 having a substitution at the aromatic ring were smoothly converted into the corresponding aryl silanes 3 in good yields by R 3 SiBPin 2 (2.0 equiv) in the presence of KOtBu (3.0 equiv) in a mixed solvent system (c-hex/THF 1/2) at room temperature. SCHEME 1 | Examples of defluorosilylation reactions of organic fluorides with R 3 SiBPin.
Frontiers in Chemistry | www.frontiersin.org October 2021 | Volume 9 | Article 771473 Heteroaromatic fluorides 1 are also accepted by the same conditions to provide heteroaromatic silanes 3 in good yields. We also carried out the same reactions under Ni-catalysis. While the yields under the catalyst-free conditions were lower than those under Ni-catalysis, the transition-metal-free system is advantageous from the perspective of green chemistry (Scheme 1F).

RESULTS AND DISCUSSION
To start the optimization, we selected 4-fluorobiphenyl (1a) and silylboronate Et 3 SiBpin (2a) as model substrates to examine the defluorosilylation reaction. Based on our earlier reported conditions of the Ni-catalyzed defluorinative silylation of aryl fluorides 1 [Et 3 SiBpin (1.5 equiv), KOtBu (2.5 equiv), 10 mol% Ni(cod) 2 in cyclohexane (c-hex)/THF (1/2, v/v) at room temperature], we carried out the reaction of 1a with 2a under the conditions mentioned above but without Ni-catalyst. All the optimizations were carried out on a 0.1 mmol scale of 1a. The expected biphenyl-4-yl-triethylsilane (3aa) was observed in 65% 1 H NMR yield after 8 h (entry 1, Table 1). To compare Uchiyama's reaction conditions (Kojima et al., 2019) (NaOtBu, THF), replacing KOtBu with NaOtBu, gave 58% yield of 3aa (entry 2). Other bases such as LiOtBu or KOMe resulted in no reaction (entries 3 and 4). The conditions by Martin  (LiHMDS, DME) were also attempted but using our solvent system (c-hex/THF 1/2, v/ v), but no reaction resulted (entry 5). Interestingly, KHMDS facilitated this defluorosilylation reaction by affording 3aa in 27% yield (entry 6). We subsequently attempted the reaction in a single solvent of c-hex, THF, or diglyme to investigate the effect of solvent. The mixed solvent system, c-hex/THF (entry 1), was more effective than others (entries 7-9). We next varied the amounts of 2a and KOtBu (entries 10 and 11) and found that 2.0 equiv of 2a and 3.0 equiv of KOtBu were the optimum amounts to afford 3aa in 74% yield (56% isolated yield; entry 11). To re-ascertain the effect of Ni(COD) 2 , we investigated the reaction using these optimized conditions (entry 11) but in the presence of Ni catalyst. The defluorosilylation reaction performed more efficiently under the optimal conditions with Ni(COD) 2 to give 3aa in 83% yield (65% isolated yield; entry 12), while 1a remained (detected by crude 19 F NMR). These comparative results thus convinced us that Ni(COD) 2 accelerates the present defluorinative transformation, while the transition-metal-free variant (entry 11) is advantageous from a green chemistry perspective.
Based on our previous work of defluorosilylation of alkyl fluorides 1 with R 3 SiBPin 2 mediated by a potassium base (Cui et al., 2018), the defluorosilylation of aryl fluorides mediated by a lithium base (Martin)  and by a sodium base (Uchiyama) (Kojima et al., 2019), the reaction should proceed the nucleophilic attack of the silyl anion involving a concerted S N Ar process. A schematic reaction of the catalyst-free defluorosilylation process is presented in Scheme 2 by considering our previous work and Uchiyama's elegant DFT calculations (Kojima et al., 2019). First, R 3 SiBPin 2 reacts with tBuOK to provide potassium silyl anion species C complexed with tBuO-BPin via A and B (Cui et al., 2018;Jain et al., 2018;Zhou et al., 2021). C approaches the aryl fluoride 1 to form the intermediate I. A concerted S N Ar reaction happens with the attack of the boron center of tBuO-BPin by another tBuOK via a transition state II with the key C-F bond cleavage to furnish the aryl silanes 3 with the formation of KF and D, K + [tBuO 2 BPin]-.

CONCLUSION
In summary, we reported a feasible transition-metal-free method for synthesizing aryl silanes 3 through the defluorosilylation of aryl fluorides 1 by using silylboronates R 3 SiBPin 2 and KOtBu. Furthermore, we compared our new results with a previous report on the success of Nicatalyzed defluorosilylation of fluoroarenes. Thus, we concluded that the transformation of aryl fluorides into corresponding aryl silanes via a C−F bond cleavage can be achieved even in the absence of Ni(COD) 2 , but in relatively lower yields than those of the Ni-catalyzed protocol, due to different reaction mechanisms. A further extension of this methodology is currently underway.

DATA AVAILABILITY STATEMENT
The original contributions presented in the study are included in the article/Supplementary Material, further inquiries can be directed to the corresponding author.

AUTHOR CONTRIBUTIONS
NS conceived the concept. JZ and ZZ optimized the reaction conditions and surveyed the substrate scope. NS directed the project. NS and JZ prepared the manuscript.

SUPPLEMENTARY MATERIAL
The Supplementary Material for this article can be found online at: https://www.frontiersin.org/articles/10.3389/fchem.2021.771473/ full#supplementary-material SCHEME 2 | A schematic of the reaction process of catalyst-free defluorosilylation of aryl fluorides 1 with R 3 SiBPin 2 in the presence of tBuOK.