# Synthetic Approaches to 1,3,4-Oxadiazole-Containing Boronic Derivatives
## 3 Synthesis of Boronic Derivatives from Reagents Containing 1,3,4-Oxadiazole Moiety
### Indirect Connection of Boron with 1,3,4-Oxadiazole Ring via Heteracyclic Linker
#### 3.3.1 Boronic Acid Derivatives of (1,3,4-Oxadiazol-2-yl)pyridines  
The pyridine ring is one of the most important heteroaromatic rings, present in many organic compounds with a wide range of applications in pharmaceuticals and agrochemicals, and is also found in certain vitamins such as B\({}_{6}\) and B\({}_{3}\)[80; 81; 82; 83]. The pyridine ring attached to the 1,3,4-oxadiazol ring was functionalized with boronic esters or acids at four possible positions (Figure 8). For clarity, boronic acids/esters located at the 6-position relative to the nitrogen (6-(1,3,4-oxadiazol-2-yl))pyridin-2-ylboronic acid (**65**)) atom are referred to as 2-pyridinylboronic acids, while those at the 5-position (5-(1,3,4-oxadiazol-2-yl))pyridin-3-ylboronic acid (**66**)) are classified as 3-pyridinylboronic acids, based on their nitrogen-boron positional relationship. There are limited reported syntheses of 1,3,4-oxadiazol-2-ylpyridine boronic acid derivatives. This is likely due to the instability of 2-pyridinyl boronic acids, which readily undergo protodeboronation [84]. To improve their stability, strategies such as the use of alternative boronate species--including \(N\)-methyliminodiacetic acid (MIDA) boronates and \(N\)-phenyldiethanolamine (PDEA) boronates--one-pot or in situ generation, or the addition of copper salts as stabilizing agents are commonly employed [84]. However, these methods have not yet been reported for the synthesis and stabilization of 1,3,4-oxadiazol-2-ylpyridine boronic acid derivatives. 2-Pyridinylboronic esters, however, are much more stable than the corresponding acids [85]. One method (Scheme 17) describes the successful Miyaura borylation (method B) of a 1,3-bis(5-(6-bromopyridin-2-yl)-1,3,4-oxadiazol-2-yl)benzene to form the desired 6,6\({}^{\prime}\)-(5,5\({}^{\prime}\)-(1,3-phenylene)bis(1,3,4-oxadiazol-5,2-diyl))bis(pyridine-6,2-diyl)diboronic acid dipinacol ester in 81% yield. This approach utilizes bis(pinacolato)diboron (B\({}_{2}\)(pin)\({}_{2}\)) as the boron source, tetrakis(triphenylphosphine)palladium(0) (Pd(PPh)\({}_{4}\)) as the catalyst, and AcOK as the base in 1,4-dioxane at 110 \({}^{\circ}\)C [86; 87]. Several studies focus on the synthesis of 1,3,4-oxadiazol-pyridine derivatives bearing a boron atom at the 3-position relative to the pyridinyl nitrogen (Figure 9) [69; 88; 89; 90; 91]. Two general approaches have been employed: Miyaura borylation (method B) and halogen-metal exchange via lithiation (method A). Table 5 summarizes the reaction conditions, cata  
Figure 8: Boronic acid derivatives and 1,3,4-oxadiazol exit vectors from pyridine linkers: 6-(1,3,4-oxadiazol-2-yl)pyridin-2-ylboronic acid (**65**), (5-(1,3,4-oxadiazol-2-yl))pyridin-3-ylboronic acid (**66**), 4-(1,3,4-oxadiazol-2-yl)pyridin-3-ylboronic acid (**67**) and 6-(1,3,4-oxadiazol-2-yl)pyridin-3-ylboronic acid (**68**). lysts, solvents, bases, and the corresponding yields, together with relevant references. The Miyaura borylation protocol involves the cross-coupling of 3-bromopicolic acid derivatives with bis(pinacolato)diboron (B\({}_{2}\)(pin)\({}_{2}\)). Common catalysts for this reaction leading to derivative 5-(1,3,4-oxadiazol-2-yl)-pyridin-3-ylboronic acid pinacol ester include Pd(dppf)Cl\({}_{2}\) (bis(diphenylphosphino)ferrocene) palladium(II) dichloride) or its DCM adduct. Solvents such as DMSO, acetonitrile, or 1,4-dioxane are typically used in conjunction with potassium acetate as the base (Table 5, Entries 1-3). Microwave irradiation can accelerate the reaction in some cases (Table 5, Entries 1-2). However, yield data are often absent from the literature. One notable exception reports a 15% yield for a reaction conducted in DMSO at 80 \({}^{\circ}\)C (Table 5, Entry 3). For 4-(1,3,4-oxadiazol-2-yl)pyridin-3-ylboronic acid pinacol ester, the synthesis involves PdCl\({}_{2}\)(PPh\({}_{3}\))\({}_{2}\) (bis(triphenylphosphine) palladium(II) dichloride), potassium acetate, and triethylamine in 1,4-dioxane at 100 \({}^{\circ}\)C, yielding the boronic ester in 76% yield (Table 5, Entry 4).