Hidroformilação de compostos de origem natural catalisada por complexos de ródio

Abstract

Transition metal catalyzed hydroformylation is one of the most powerful tools for the formation of carbon-carbon bonds in organic synthesis. In the present work, the rhodium catalyzed hydroformylation of α-terpineol, terpinen-4-ol, α-bisabolol, α-ionone, limonene, β-caryophyllene and cis-jasmone was studied aiming to convert these natural substrates into more functionalized compounds, which could be interesting for pharmaceutical, fragrance and flavor applications. The effects of reaction variables, such as temperature, carbon monoxide and hydrogen pressure, nature of solvent, nature of phosphorous ligands and their concentrations, were evaluated to achieve better performance of the catalytic system. Successful hydroformylation of the trisubstituted endocyclic double bonds in α-terpineol and terpinen-4-ol molecules could be performed only under relatively drastic conditions: 120 °C and 80 atm of the gas mixture. In spite of that, two major aldehydes were obtained with high combined selectivity from both substrates, either in the presence of tris(2,4-di-tert-butylphenyl)phosphite or in the absence of any phosphorus ligand. Under similar conditions, it was also possible to promote the hydroformylation of α-ionone, despite the low reactivity presented by this compound, and to reach approximately 80% of combined selectivity for the products of this reaction. The results obtained in the study of the hydroformylation of α-bisabolol were not satisfactory due to the low selectivity for the products of interest. On the other hand, the double hydroformylation of limonene and β-caryophyllene was performed by a procedure consisting of two consecutive steps at different temperatures allowing for high selectivity for the formation of dialdehydes. More sustainable methods were also developed by the use of environmentally friendly solvents such as diethylcarbonate, 2-methyltetrahydrofuran, p-cymene and anisole, alternatively to toluene. Furthermore, the hydroformylation of cis-jasmone was performed successfully to give two major aldehydes. This compound was reactive even in the absence of auxiliary phosphorus ligands, but with relatively low selectivity for carbonylated products due to the significant substrate isomerization. In toluene solutions, the use of triphenylphosphine and tris(2,4-di-tert-butylphenyl)phosphite as auxiliary ligands was beneficial for the catalytic performance of the system. Through the application of tandem catalytic processes, the aldehydes derived from cis-jasmone were converted into new compounds. The use of ethanol as a solvent promoted the acetalization of the aldehydes, without the need for acid additives; while the use of morpholine and 4-methylpiperidine as additional reagents enabled the formation of the corresponding amines through hydroaminomethylation.