G4 Doctoral dissertation (monograph)
2,5-diarylpyrrolidines and pyroglutamic-acid-derived 2-diarylmethyl-5-aryl-pyrrolidines : their synthesis and use in asymmetric synthesis (2020)

Kortet, S. (2020). 2,5-diarylpyrrolidines and pyroglutamic-acid-derived 2-diarylmethyl-5-aryl-pyrrolidines : their synthesis and use in asymmetric synthesis [Doctoral dissertation]. Jyväskylän yliopisto. JYU dissertations, 337. http://urn.fi/URN:ISBN:978-951-39-8465-6

JYU authors or editors

Publication details

All authors or editors: Kortet, Sami

eISBN: 978-951-39-8465-6

Journal or series: JYU dissertations

eISSN: 2489-9003

Publication year: 2020

Number in series: 337

Number of pages in the book: 1 verkkoaineisto (221 sivua)

Publisher: Jyväskylän yliopisto

Place of Publication: Jyväskylä

Publication country: Finland

Publication language: English

Persistent website address: http://urn.fi/URN:ISBN:978-951-39-8465-6

Publication open access: Openly available

Publication channel open access: Open Access channel

Abstract

Pyrrolidine is a nitrogen-containing heterocycle, and various natural products contain this five-membered structure. It is also present in chiral organocatalysts, which are used in asymmetric synthesis. Examples of such compounds include proline, the Hayashi–Jørgensen catalyst, 2,5-diarylpyrrolidines and pyroglutamic-acid-derived 2-diarylmethyl-5-aryl-pyrrolidines. The latter two are in the focus of this dissertation, and in Chapters two and three, compendiums of the synthesis strategies and routes of the pyrrolidines are presented. The routes are categorised based on the retrosynthetic scissions, critical for the formation of the 2,5-disubstituted pyrrolidine cores. Lastly, the usefulness of these pyrrolidines in the field of asymmetric synthesis is summarised. Chapter four describes the method development of an iminium-catalysed Mukaiyama–Michael reaction, the focus being in the organocatalyst optimisa-tion. 2,5-diarylpyrrolidines and pyroglutamic-acid-derived 2-diarylmethyl-5-aryl-pyrrolidines were prioritised in the research. Eventually, an excellent level of enantioselectivity was reached by using a 2,5-diarylpyrrolidine catalyst, equipped with strongly electron-withdrawing substituents. In the fifth chapter, the above-mentioned reaction was utilised as the key transformation in a total synthesis route of an amino acid, (+)-lycoperdic acid. With another organocatalytic reaction, namely an enamine-catalysed α-chlorination, the full stereocontrol of the stereogenic centers was achieved. The target natural product was synthesised in nine steps from a commercially available compound. The last chapter compiles together additional studies related to the 2,5-diarylpyrrolidine synthesis and the Mukaiyama–Michael reaction of interest. An alternative way to reduce 1,4-bis(aryl)butane-1,4-diones enantioselectively was studied, and commercially available ketoreductase enzymes gave encour-aging results. Studies for replacing acrolein with its diethyl acetal in the stud-ied Mukaiyama–Michael reaction were started with promising results. Lastly, another type of pyrrolidine organocatalyst, which gave eventually the best er in the above-mentioned reaction, was found.

Keywords: organic compounds; amines; amino acids; naturally occurring substances; chemical synthesis; catalysis; catalysts

Free keywords: Mukaiyama–Michael reaction; asymmetric natural product total synthesis; pyrrolidines; organocatalysis; lycoperdic acid

Contributing organizations

Ministry reporting: Yes

Reporting Year: 2020