Reaction optimization. We began our study with the electrochemical deaminative borylation using alkyl triflimidate (1) and B2cat2 (2) and treated under constant current electrolysis (CCE) (Table 1). After detailed investigations, we found that the desired alkyl boron (3) could be obtained in 88% yield under an undivided cell set-up with magnesium anode and nickel foam cathode in a working current of 20 mA (Table 1, entry 1). Other anode materials, such as zinc, iron, and carbon were unable to provide higher reaction efficiency (entries 2–4). In the case of carbon as the cathode, a lower yield of 36% is observed (entry 5). Notably, the use of nBu4NBF4 instead of TBAI proved incompatible, which indicated that the reaction could be mediated by alkyl iodide (entry 6). Varied current (10 mA and 30 mA) caused decreased yields of the product (Table 1, entries 8 and 9). The presence of air leaded to a product loss of approximately 15% (entry 7). Remarkably, activation of the primary alkyl amine with TsCl and preparation as Katritzky salt proved to be impractical under the given reaction conditions, leading to significant challenges in achieving the desired target product.(entries 10 and 11).
With the optimized conditions in hand, the generality of this electrochemical transformation has been evaluated. As shown in Fig. 2, this protocol exhibited good efficiency toward the borylation of alkyl triflimidates, showcasing wide functional tolerance and generated the borylation products in moderate to high yields. Notably, various functional groups, including halides (4–5, 8–9, 25), trifluoromethyl (6–7), ethers (14, 16), ester (24), aromatic and heterocyclic (11–13, 17–20), naphthalene ring (21), cyanides (15, 31), protected alcohol (29), and thioether (32), have demonstrated compatibility with this electrochemical scheme. This underscores the robustness of our electrochemical methodology. Additionally, recognizing the crucial role of polyboron compounds in organic synthesis and the limitations of direct synthesis methods, this paper outlines the preparation of diverse diboron compounds through diamine (26, 30). We next extended this borylation reaction to secondary alkyl amines. Secondary amines were also amenable to this method, as exemplified by 2-Amino-4-phenylbutane, which gave product 33 in 45% yield. Cyclic alkylamines, such as cyclohexyl, cyclododecyl, and 4-aminotetrahydropyran, also result in moderate yields of the boronated products (34–36).
Having successfully established the C − B bond, we explored the possibility of forming other C − X bonds within this framework. Disulfide is selected as the radical receptor. As depicted in Fig. 3, under the standard conditions, we found both alkyl and aryl sulfide were generated in high yields (37, 41–44). In addition, we efficiently achieved deaminative selenation (38), stibnation (39), and sulfonylation (40), resulting in high yield products.
To further demonstrate the practicality of the deaminative functionalization approach for alkyl triflimidates, we conducted various deamination reactions. As illustrated in Fig. 4, halogenation (Cl, Br, I) achieved comparable conversion rates (46–48). Furthermore, under catalytic base conditions and heating at 60°C, the deaminative oxidation of alkyl triflimidate 1 successfully yielded the corresponding ethers (49). Reaction of alkyl triflimidates with amides led to the formation of ester compounds (50–53). Notably, alkyl triflimidates facilitated deamination Ritter reactions, efficiently producing a diverse array of amide compounds, including alkyl and aryl amides (54–61).
To explore the reaction mechanism, a series of experiments were conducted. The intermediate verification experiment demonstrated that alkyl triflimidate (5a) was completely converted to alkyl iodide (5b) within 2 mins, followed by the consumption of 5b and its conversion into the corresponding product within 40 mins (Fig. 5A). The in-situ 19F NMR also indicated that the iodination of 5a was rapid (Fig. 5B).47–48 The radical trapping experiment with TEMPO under standard conditions resulted in the alkyl adduct 45, which was detected by HRMS. This observation validated the radical mechanism (Fig. 5E). The CV experiments were performed to verify the species undergoing cathodic reduction. The reduction potential of the alkyl triflimidate 8a (-3.6 V) was higher than that of the iodide 8b (-3.1 V), with the reduction potential of B2cat2 (-3.4 V) falling between the two, indicating that the direct reduction of alkyl triflimidate to radicals is challenging, whereas 8b is more likely to be reduced to generate alkyl radicals, according to the literature (Fig. 5C).49–50 To further improve the reaction efficiency, the microfluidic electrochemistry platform was introduced for scale-up reactions. Under a flow rate of 0.025 mL/min and an electrolysis current of 10 mA, we obtained a yield of 76% for the product (Fig. 5D). To validate the applicability of this protocol, a 3 mmol-scale reaction was carried out, yielding the boronated product in 75% within 5 hours at 100 mA (Fig. 5F). Furthermore, utilizing a one-pot synthesis approach, we were able to achieve a 43% yield of the boronated product, demonstrating the practicality of this method under the given reaction conditions (Fig. 5G).
Based on the previous reports and the above experiments, we propose a possible mechanism as shown in Fig. 5H.51–55 The reaction is initiated with rapid iodination of alkyl triflimidate to generate alkyl iodide. Meanwhile, the DMA combines with one equivalent of B2cat2 to form complexe A and undergoes single-electron reduction at the cathode to form radical B. Subsequently, this radical may undergo two different paths. In path a, the reaction of the alkyl radical with A gives the alkyl boronate product and C/D, which is eventually oxidized on the anode to form E. In path b, radical − radical cross-coupling of alkyl radical and B furnishes the alkyl boronate and complex F.