Synthesis and properties of guanidine cocatalysts prepared by cycloadition reactions

Abstract

U sklopu ove disertacije razvijene su metode za sintezu novih polickličkih gvanidina. Pri tome je istražen utjecaj strukture gvanidinske skupine i tipa dienofila na uspješnost reakcije cikloadicije i moguća uloga protona kao zaštitne skupine. Derivati maleinske kiseline daju smjesu egzo i endo produkata neovisno o primijenjenom sintetskom pristupu. Cikloadicija furfuril-gvanidina na dimetil-acetilendikarboksilat daje ciljane produkte u dobrim prinosima uz djelomičnu konverziju u tri- ili tetracikličke derivate. Objašnjena je i pojava aza- Michaelove adicije kao nusreakcije uzrokovane nukleofilnošću aniona. Mehanizmi reakcija su istraženi i DFT kvantno kemijskim proračunima. Novim spojevima je ispitana kokatalitička aktivnost u aldolnoj reakciji kataliziranoj (S)-prolinom. Opaženo je povećanje selektivnosti i iskorištenja reakcije pri čemu se ističe rezultat od 98:2 omjer dijastereoizomera, uz enantiomerni suvišak >99,5 % i prinosom od 97 % pri 0°C. Najbolji kokatalizator je ispitan u Knoevenagelovoj reakciji gdje je primijećena slaba aktivnost, značajno manja nego kod strukturno sličnog 1,5,7-triazabiciklo[4.4.0]dec-1-ena.As part of this dissertation, methods for the synthesis of new polycyclic guanidines were developed. The influence of the guanidine structure and the type of dienophile on the success of the cycloaddition reaction and the possible role of protons as a protective group were investigated. Maleic acid derivatives give a mixture of exo and endo products regardless of the synthetic methods employed. The cycloaddition of furfuryl-guanidine to dimethyl acetylenedicarboxylate produces the target products together with three- or tetracyclic derivatives in good yields. Aza-Michael addition as a side reaction caused by the nucleophilicity of anions is also explained. Reaction mechanisms were investigated by DFT quantum chemical calculations. The cocatalytic activity of the new compounds was tested in aldol reaction catalyzed by (S)-proline. An increase in the selectivity and yield of the reaction was observed, with the best result of 98:2 diastereoisomer ratio, with an enantiomeric excess of >99.5% and a yield of 97% at 0 °C. The best cocatalyst was tested in the Knoevenagel reaction where a poor activity, significantly lower than for 1,5,7-triazabicyclo[4.4.0]dec-1-ene, was observed