Organokatalizirana spiroheterociklizacija arilidenskih derivatov pirolona z 1,4-ditian-2,5-diolom

Gnidovec, Jan (author), Grošelj, Uroš (mentor)

Optimiziral sem organokatalizirano sulfa-Michaelovo/aldolno kaskadno reakcijo med benzilidenskim derivatom pirolona in 2-merkaptoacetaldehidom. Pri optimalnih reakcijskih pogojih sem iz heteroarilidenskih derivatov pirolin-4-onov pripravil knjižnico desetih spirocikličnih spojin. Reakcije so v večini primerov potekle izredno stereoselektivno (do >99% ee, dr 96:4), produkti so bili izolirani s solidnimi izkoristki (32–84%). Produkti vsebujejo spirociklične, pirolonske in tetrahidrotiofenske motive, ki pogosto izražajo biološko aktivnost. Iz aminokislinskih gradnikov sem sintetiziral pirolin-4-onom sorodno tetramsko kislino in njen benzilidenski derivat. Slednjega sem uporabil v dveh organokataliziranih pretvorbah z 1,4-ditian-2,5-diolom in izoliral spirociklični produkt. Uporaba dveh različnih katalizatorjev je privedla do nastanka popolnoma različnih diastereomerov.

• Language: Slovenian
• Keywords: asimetrična sinteza, organokataliza, bifunkcionalna kataliza, piroloni, 1, 4-ditian-2, 5-diol, spiroheterocikli, tetramska kislina.
• Work type: Master's thesis/paper
• Typology: 2.09 - Master's Thesis
• Organization: FKKT - Faculty of Chemistry and Chemical Technology
• Year: 2019
• PID: 20.500.12556/RUL-109429
• COBISS.SI-ID: 1538324675
• Publication date in RUL: 02.09.2019

Secondary language

• Language: English
• Title: Organocatalyzed spiroheterocyclization of arylidene-pyrrolone derivatives with 1,4-dithiane-2,5-diole

Abstract

Optimization of organocatalyzed sulfa-Michael/aldol cascade reaction of benzylidene-pyrrolone derivative using 2-mercaptoacetaldehyde was carried out. Under optimized reaction conditions, a library of 10 spirocyclic compounds was synthesized from respective heteroarylidene-pyrroline-4-ones. Reactions proved to be highly stereoselective (up to >99% ee, dr 96:4), yielding decent amounts of isolated spirocyclic compounds (32–84%). The end products contain spirocyclic, pyrrolone and tetrahidrothiophene motifs that frequently exhibit biological activity. Amino acid building blocks have been used to synthesize pyrroline-4-one related tetramic acid and its benzylidene derivative. Benzylidene-tetramic acid has been subsequently reacted with 1,4-dithiane-2,5-diol in the presence of an organocatalyst yielding a novel spirocyclic product. The application of two different organocatalysts led to the formation of two different diastereomers.

• Keywords: asymmetric synthesis, organocatalysis, bifunctional catalysis, pyrrolones, 1, 4-dithiane-2, 5-diol, spiroheterocycles, tetramic acid.