Cesium carbonate is an inorganic compound with the chemical formula Cs2CO3. It is a white solid at room temperature and pressure. It is very soluble in water and absorbs moisture quickly in the air. Its aqueous solution is strongly alkaline, which is mainly attributed to the fact that cesium carbonate can ionize cesium ions and carbonate ions in water, and carbonate ions react with water molecules to form hydroxide ions and bicarbonate ions, which increases the pH value of the aqueous solution and thus shows alkalinity.
Carbon dioxide (CO2) is a rich, non-toxic and sustainable carbon resource. Its efficient conversion to synthesize a variety of high-value-added chemicals has attracted widespread attention from chemists. In the past few decades, researchers have developed a series of methods to convert CO2 into a variety of carboxylic acid compounds, but due to the thermodynamic stability and kinetic inertness of CO2 itself, its conversion usually requires harsh conditions. Although there have been some reports on asymmetric catalytic conversion of CO2 in recent years, most of them focus on the construction of central chirality, and there are few studies on the construction of axial chiral carbonyl compounds using asymmetric carboxylation reactions of CO2.
Using a photo/palladium synergistic catalytic system and cesium carbonate as a base, a tandem asymmetric carboxylation and in situ esterification reaction of heteroaromatic ring (quasi) halides with CO2 and alkyl bromides was developed. Through a dynamic kinetic asymmetric transformation process, the efficient and highly selective synthesis of axial chiral esters with CO2 was successfully achieved.
The researchers used 1-(2-bromonaphthalene-1-yl)isoquinoline 1a and 1-bromohexane 2a as template substrates, 4CzIPN as a photocatalyst, Pd(acac)2 as a palladium catalyst precursor, (R)-BTFM-Garphos (L1) as a chiral ligand, DIPEA as a reducing agent, cesium carbonate as a base, lithium bis(trifluoromethanesulfonyl)imide and 4Å molecular sieves as reaction additives, and N, N-dimethylacetamide as a solvent. Under an atmospheric pressure CO2 atmosphere and 455 nm blue light irradiation, the reaction was carried out at 16 °C for 24 hours, and the product was obtained with an isolated yield of 89% and an ee value of 96%. Under the optimal reaction conditions, the researchers first investigated the scope of application of alkyl bromide substrates. Various functional groups on various alkyl bromides, such as fluorine, chlorine, methoxy, trifluoromethyl, phosphonate groups, and some drug molecular fragments, all have good compatibility.
Subsequently, the researchers also investigated heteroaromatic ring halides. Various substituents at different positions of the naphthalene ring have little effect on the reaction, and the corresponding products can be obtained with good to excellent yields and excellent enantioselectivity.
In order to gain a deeper understanding of the reaction mechanism, the researchers designed a series of control experiments to study the reaction mechanism, including fluorescence quenching experiments, cyclic voltammetry experiments, free radical quenching and free radical clock experiments, reaction kinetics experiments, and product racemization kinetics experiments. The experimental results show that: (1) The reaction involves a tandem enantioconvergent carboxylation/substitution esterification process catalyzed by photoredox/transition metal coordination; (2) The carboxylate anion produced by the carboxylation reaction is rapidly captured in situ by the alkyl bromide, thereby generating a conformationally stable axial chiral ester, which is one of the key factors for the high enantioselectivity of the reaction.
