Application background and overview of ferrocene boric acid
The disclosure of the ferrocene structure was an important breakthrough in the field of chemistry and promoted the birth and development of modern metal-organic chemistry. Ferrocene quickly attracted scientists to think about its fascinating chemical properties. Researchers began developing synthetic methods using ferrocene derivatives and found their use in a wide range of scientific fields. In fact, more than 60 years after the discovery of ferrocene, ferrocene chemistry is still a very active area of research. The reasons for this long-term and sustained interest in ferrocene are multifactorial. First, ferrocene has a perfect sandwich structure, which breaks the traditional understanding of the nature of metal-carbon bonds. On the other hand, ferrocene and its derivatives display unusual stability against moisture, oxygen, and many chemicals, as well as other unique electrochemical properties. Currently, commonly used reagents for introducing ferrocene groups into molecules include ferrocene, ferrocene formaldehyde, etc. The above reagents are mostly used for the formation of carbon-carbon bonds. As a commercial reagent, ferrocenylboronic acid can be used not only for the construction of carbon-carbon bonds, but also for the construction of chemical bonds containing heteroatoms such as boron-silicon bonds and carbon-sulfur bonds. At the same time, compared with other ferrocene reagents, ferrocene boronic acid has obvious advantages in reaction steps and atom economy in transition metal-catalyzed coupling reactions. Therefore, ferrocenylboronic acid is widely used in the synthesis of ferrocene derivatives.
Application and preparation of ferrocenylboronic acid
A method for synthesizing ferrocenylboronic acid, the specific steps are as follows:
a) Synthesis of lithium ferrocene salt: use ferrocene as raw material, react with n-butyllithium in anhydrous ether solvent at 0-40 degrees to obtain the lithium salt of ferrocene;
b) Synthesis of ferrocene boronic acid: Add B(OR)3 to the lithium salt solution of ferrocene in a) at ‑78～‑50 degrees, where R is an alkane After adding the base, naturally raise the temperature to room temperature, stir for 2-15 hours, then add alkaline aqueous solution to quench the unreacted n-butyllithium, separate the liquids, wash the organic phase once with alkaline aqueous solution, and adjust the pH of the aqueous phase with acid =6-7, precipitate crude ferrocene boric acid, filter with suction and wash with water twice to obtain a mixture of 1-ferrocene monoboric acid and 1,1′-ferrocene diboric acid;
Applications of ferrocenylboric acid
1. Coupling reaction of ferrocenylboronic acid and iodinated aromatic hydrocarbons
There are studies reporting the coupling reaction of ferrocenylboronic acid and iodoarenes to prepare chiral asymmetric substituted binaphthyl. This experiment uses tetrakis triphenylphosphine palladium as the catalyst, sodium carbonate as the base, and the reaction solvent is dioxane Ring/water mixed solvent system, the reaction temperature was 109-120°C, the reaction lasted for 4 days, and the yield of coupling product 3 was 27%. The research group also performed a coupling reaction between ferrocenylboronic acid 1 and diiodoarene 4 under similar reaction conditions, using potassium phosphate as a base and a reaction temperature of 70°C, to obtain coupling product 5 with a yield of 38%. . Although the yield of this method is average, the coupling reaction using ferrocenylboronic acid is the shortest and most economical synthesis route for the synthesis of chiral asymmetric binaphthyl compounds.
2. Coupling reaction of ferrocenylboronic acid and brominated aromatics
Ferrocenyl anthraquinone 10 was prepared by reacting ferrocenylboronic acid 6 with bromoanthraquinone 9, with a yield of 91%. The reaction conditions are: the catalyst is Pd (PPh3) 4, the base is potassium carbonate, the solvent is DMF, reflux for 20 minutes, then stir at room temperature in the dark for 2 days. This report is the first to utilize direct polymerization of ferrocenyl anthraquinone to generate anthracene polysulfide polymers. In 2015, a coupling reaction of ferrocenylboronic acid 6 and dibromoarene 11 was reported. The reaction used sodium hydroxide as the base, dioxane as the solvent, and refluxed for 16 hours to obtain a good yield. The reaction product 12 can regulate the steric interaction between the two ferrocenes through thioether.
1) Coupling reaction of ferrocenylboronic acid and iodinated heterocyclic aromatic hydrocarbons
Aryl-substituted pyridine 22 was prepared by the coupling reaction of ferrocene boronic acid 6 and iodopyridine 21. Potassium bicarbonate was used as the base. The reaction temperature was 110°C and the yield was 88%. Experiments have shown that the preparation of aryl-substituted pyridine using a coupling reaction involving ferrocene boronic acid has good reaction yield and functional group compatibility, and is a simple and efficient synthesis method.
2) Coupling reaction of ferrocenylboronic acid and brominated heterocyclic aromatic hydrocarbons
Dipyridine-substituted ferrocene 24 was prepared by reacting 1,1’-ferrocene diboronic acid 6a with dimethyl sulfoxide 3-bromopyridine 23. The reaction conditions are: sodium carbonate and sodium hydroxide are bases, the reaction solvent is dioxane/water, the reaction is refluxed for 24 hours, and the yield is 68%. Studies have shown that due to π-π stacking, the pyridine substituent in the reaction product is in the π-stacked rotamer dominant conformation; when product 24 is quaternized, the pyridinium group is in the π-stacking configuration due to electrostatic repulsion. The stack is completely rotated away from the dominant conformation. Such compounds have broad application prospects in the field of developing and constructing electrostatically driven ferrocene platform molecular motors.
3. Other reactions involving ferrocenylboronic acid
1) Reaction of ferrocenylboronic acid and aromatic aldehydes
Nucleophilic addition reaction of ferrocenylboronic acid and aromatic aldehydes: One-pot asymmetric nucleophilic addition reaction of ferroceneboronic acid 6 and benzaldehyde. The reaction first utilizes ferrocenylboronic acid and diethylzinc to perform a metal transfer reaction to generate ferrocenezinc reagent. Subsequently, the asymmetric nucleophilic addition reaction of ferrocene zinc reagent with benzaldehyde was induced by the chiral binaphthyl-derivatized aminoalcohol 31 to generate the chiral diarylThe base alcohol is 32, the reaction yield is 91%, and the ee is 61 (S). The reaction process is shown in the figure.
Usually, in order to obtain higher enantioselectivity, the preparation of diarylzinc reagents requires the use of lithium reagent Grignard reagents for metal transfer reactions, which is very difficult. Due to the high reactivity of lithium and magnesium intermediates, many functionalized diarylzinc reagents have not yet been prepared. The preparation of diarylzinc reagents was successfully achieved by using arylboronic acid and diethylzinc; by changing the structure of the nucleophile and aldehyde, asymmetric diarylcarbinols can be prepared in one step. This reaction method is important in the field of biomedicine. application value.
Coupling reaction of ferrocenylboronic acid and aromatic aldehydes: reaction of ferroceneboronic acid 6 and aromatic aldehydes to prepare ferrocene alcohol ester. The reaction uses N-heterocyclic carbene 33 as the catalyst, cesium carbonate as the base, and toluene as the solvent. The reaction takes place in the air for 3 to 6 hours. The reaction temperature is 50°C or 70°C. The product has a medium reaction yield. The reaction formula is shown in the figure. 5. Typically ferrocene alcohol esters are prepared by reacting ferrocene iodide with carboxylic acids under copper(II) catalysis. A series of ferrocene alcohol ester compounds that cannot be synthesized by other reactions were prepared using the reported method. First, carbene reacts with the carbonyl group of the aromatic aldehyde to form intermediate II, and then intermediate II reacts with oxygen and boric acid to form intermediate II. The aryl group in intermediate II quickly transfers to the peroxy bond and forms a borate anion ( Ⅲ). Finally, intermediate III decomposes into the target product and boronic acid, and the carbene returns to the catalytic cycle.
2) Reaction of ferrocenylboronic acid and alkylsilanol
Using the dehydration reaction of ferrocenylboronic acid 6 and tert-butylsilanetriol 34 to generate cage-like borosiloxane compound 35. See the reaction diagram.
The reaction conditions were toluene refluxing for 15 hours, and the reaction yield was 82%. Such three-dimensional compounds can be used for the controllable preparation of molecular scaffolds.
3) Reaction of ferrocenylboronic acid and sodium arylthiosulfonate
A copper(II)-catalyzed direct oxidative cross-coupling reaction between ferrocenylboronic acid 6 and p-chlorophenyl sodium thiosulfate 36 was reported in 2015. The reaction cyanopyridine formula is shown in the figure:
The reaction conditions are: copper chloride is used as the catalyst, the oxidant is DTBP, other additives are silver carbonate A, potassium phosphate and o-phenanthroline, the reaction solvent is DMF, the reaction is carried out at 80°C for 7 hours, and the yield of the product is 37 is 62%. Research shows that carbon dioxide can effectively inhibit the formation of disulfide by-products. This reaction provides an effective way to develop new sulfur-containing ferrocene ligands.
4) Reaction of ferrocenylboronic acid and trifluoroacetate
Some studies have reported the reaction of ferroceneboronic acid 6 and gold trifluoroacetate complex 38 to prepare metallocycloboroxane. The reaction was carried out using KtOBu as base and toluene as solvent. The reaction was carried out at room temperature for 3 hours. The yield of product 39 was 72%. Metalloborane derivatives are usually prepared by heavy metal-catalyzed coupling reactions or high-temperature heating reactions. This study provides a simple, mild, and efficient method for the preparation of gold (III) borane derivatives.
