Pd/C-CATALISED HYDROGENIZATION OF METHYL PYRROLE-3-CARBOXYLATES IN THE DIASTEREOSELECTIVE SYNTHESIS OF α-SUBSTITUTED β-PROLINES
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Keywords

pyrrol-3-carboxylates, Pd/C-catalised hydrogenization, diastereoselective synthesis, β-prolines.

How to Cite

Kemskiy, S., Grozav, A., Sujkov, S., Yurchenko, O., & Vovk, M. (2020). Pd/C-CATALISED HYDROGENIZATION OF METHYL PYRROLE-3-CARBOXYLATES IN THE DIASTEREOSELECTIVE SYNTHESIS OF α-SUBSTITUTED β-PROLINES. Ukrainian Chemistry Journal, 86(2), 100-110. https://doi.org/10.33609/0041-6045.86.2.2020.100-110

Abstract

The analysis of synthetic and biological importance of α-substituted β-prolines was conducted. Methods of synthesis of β-prolines and their esters, based on both intra- and intermolecular reactions of formation of functionalized pyrrolidinic cycle, as well as catalytic reduction of corresponding 2,3-substituted pyrroles and their dihydro derivatives, were systematized. The necessity of the hydrogenation process improvement of 2,3-di-substituted pyrroles using cheap catalysts was justified. The approach to α-substituted β-prolines (2-substituted pyrrolidine-3-carboxylic acids) was pro-posed, the first stage of which is N-Boc-protection of 2-substituted pyrrolidine-3-carboxylates with di-tert-butyl dicarbonate (Boc-anhydride) in the dichloromethane solution at the room temperature in presence of catalytic amounts of N,N-dime-thylaminopyridine. Obtained derivatives were subjected to hydrogenation in the autoclave at 45 atm. at 40 oC for 20 hours in presence of 10 % Pd/C catalyst. It was found, that reaction at such conditions proceeds with the full conversion of starting compounds and demonstrates high stereoselec-tivity and leads to the mixture of diastereomeric N-Boc-protected pyrrolidine-3-carboxylates of cis- and trans-configurations with corresponding contents of 84–87 % and 13–16 % according to NMR 1Н and chromato-mass spectra. The mild hydrolysis of isolated reaction mixtures in the water solution of lithium hydroxide followed by neutrali-zation and N-Boc-deprotection with 15 % hydrochloric acid allows isolating pure major diaste-reomers of α-substituted β-prolines with 69–74 % yields. Their trans-configuration was reliably confirmed by NMR 1Н spectroscopy using the NOESY experiment.

https://doi.org/10.33609/0041-6045.86.2.2020.100-110
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