Digitala Vetenskapliga Arkivet

Change search
CiteExportLink to record
Permanent link

Direct link
Cite
Citation style
  • apa
  • ieee
  • modern-language-association-8th-edition
  • vancouver
  • Other style
More styles
Language
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Other locale
More languages
Output format
  • html
  • text
  • asciidoc
  • rtf
Construction of Five-Membered Heterocyclic Compounds via Radical Cyclization
Uppsala University, Teknisk-naturvetenskapliga vetenskapsområdet, Chemistry, Department of Chemistry.
2003 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

This thesis describes how radical cyclization chemistry can be applied for the construction of heterocyclic compounds.

In the first part, a series of electron deficient α-phenylselenenylalkenes were prepared via a PhSeCl-addition/HCl-elimination sequence. Allyl- and propargylamines readily underwent conjugate addition to these species to produce pyrrolidines or dihydropyrrol derivatives, after triethylborane initiated reductive radical cyclization in the presence of tris(trimethylsilyl)silane.

The second part describes a convergent synthesis of the pineal hormone melatonin. The indole nucleus is secured via a tris(trimethylsilyl)silane mediated 5-exo radical cyclization. The protocol provides convenient and simple access to compounds useful for studies of biological activity and structure activity relationships.

The third part describes construction of substituted tetrahydrofuran-3-ones and pyrrolidin-3-ones. Regioselective ring-opening of epoxides or aziridines with benzeneselenolate/tellurolate, followed by Michael addition to electron deficient alkynes afforded the corresponding O/N-vinylated compounds. The tetrahydrofuran-3-ones and pyrrolidin-3-ones were secured via radical carbonylation/reductive cyclization using pressurized carbon monoxide (80 atm).

The fourth part is concerned with the effect of an N-protecting group on the cyclization of 2-substituted-3-aza-5-hexenyl radicals. Relative energies for reactants and transition states were determined using density functional calculations. Reactant and transition state conformers leading to cis-product were lower in energy than those leading to trans-product. The results can be explained by the unfavorable 1,2-strain present in chair-equatorial and boat-equatorial conformers.

Place, publisher, year, edition, pages
Uppsala: Acta Universitatis Upsaliensis , 2003. , p. 59
Series
Comprehensive Summaries of Uppsala Dissertations from the Faculty of Science and Technology, ISSN 1104-232X ; 845
Keywords [en]
Organic chemistry, radical, cyclization, carbonylation, melatonin, pyrrolidine, pyrrolidin-3-one, tetrahydrofuran-3-one
Keywords [sv]
Organisk kemi
National Category
Organic Chemistry
Research subject
Organic Chemistry
Identifiers
URN: urn:nbn:se:uu:diva-3429ISBN: 91-554-5648-0 (print)OAI: oai:DiVA.org:uu-3429DiVA, id: diva2:162772
Public defence
2003-06-04, B42, BMC, Uppsala, 10:15
Opponent
Supervisors
Available from: 2003-05-12 Created: 2003-05-12Bibliographically approved
List of papers
1. A Radical Cyclization Route to Pyrrolidines Based on Conjugate Addition to Electron Deficient Phenylselenenylalkenes
Open this publication in new window or tab >>A Radical Cyclization Route to Pyrrolidines Based on Conjugate Addition to Electron Deficient Phenylselenenylalkenes
2000 In: Tetrahedron Letters, Vol. 41, no 19, p. 3701-3704Article in journal (Refereed) Published
Identifiers
urn:nbn:se:uu:diva-90418 (URN)
Available from: 2003-05-12 Created: 2003-05-12Bibliographically approved
2. Efficient Route to the Pineal Hormone Melatonin by Radical-Based Indole Synthesis
Open this publication in new window or tab >>Efficient Route to the Pineal Hormone Melatonin by Radical-Based Indole Synthesis
2003 (English)In: Synthetic Communications, ISSN 0039-7911, E-ISSN 1532-2432, Vol. 33, no 20, p. 3631-3641Article in journal (Refereed) Published
Abstract [en]

The hormone melatonin, which is known to have a range of important biological effects, has been prepared in a high-yielding route that features formation of the indole nucleus by radical cyclization. Mediation of the radical cyclization by tristrimethylsilylsilane (TTMSS) is more efficient than by N-ethylpiperidine hypophosphite.

National Category
Natural Sciences
Identifiers
urn:nbn:se:uu:diva-90419 (URN)10.1081/SCC-120024751 (DOI)
Available from: 2003-05-12 Created: 2003-05-12 Last updated: 2017-12-14Bibliographically approved
3. Construction of Tetrahydrofuran-3-ones from Readily Available Organochalcogen Precursors via Radical Carbonylation/Reductive Cyclization
Open this publication in new window or tab >>Construction of Tetrahydrofuran-3-ones from Readily Available Organochalcogen Precursors via Radical Carbonylation/Reductive Cyclization
2002 In: Organic Letters, Vol. 4, p. 3-6Article in journal (Refereed) Published
Identifiers
urn:nbn:se:uu:diva-90420 (URN)
Available from: 2003-05-12 Created: 2003-05-12Bibliographically approved
4. Radical Carbonylation/Reductive Cyclization for the Construction of Tetrahydrofuran-3-ones and Pyrrolidin3-0nes
Open this publication in new window or tab >>Radical Carbonylation/Reductive Cyclization for the Construction of Tetrahydrofuran-3-ones and Pyrrolidin3-0nes
In: Journal of Organic ChemistryArticle in journal (Refereed) Submitted
Identifiers
urn:nbn:se:uu:diva-90421 (URN)
Available from: 2003-05-12 Created: 2003-05-12Bibliographically approved
5. On the origin of cis selectivity in the cyclization of N-protected 2-substituted 3-aza-5-hexenyl radicals: a density functional study
Open this publication in new window or tab >>On the origin of cis selectivity in the cyclization of N-protected 2-substituted 3-aza-5-hexenyl radicals: a density functional study
Show others...
2004 (English)In: Journal of Organic Chemistry, ISSN 0022-3263, E-ISSN 1520-6904, Vol. 69, no 5, p. 1487-1491Article in journal (Refereed) Published
Abstract [en]

Cyclization of the N-dimethylphosphinoyl-2-methyl-3-aza-5-hexenyl radical has been studied at the UB3LYP/6-31+G(d)//UB3LYP/6-31G(d) hybrid density functional level. The corresponding radical precursor has been synthesized and found to give cis/trans ratios of up to 10/1 in reductive radical cyclizations. The relative energies of reactant and transition state conformers were determined. In discord with the Beckwith-Houk model, it has been found that chair-axial transition states, which lead to cis products, are lowest in energy, rationalizing the observed experimental diastereoselectivity.

National Category
Natural Sciences
Identifiers
urn:nbn:se:uu:diva-90422 (URN)10.1021/jo030294h (DOI)14987001 (PubMedID)
Available from: 2003-05-12 Created: 2003-05-12 Last updated: 2017-12-14Bibliographically approved

Open Access in DiVA

fulltext(903 kB)5598 downloads
File information
File name FULLTEXT01.pdfFile size 903 kBChecksum SHA-1
2a6fab906ee31484b924a3c4400af92d2902587a57160960280bf0146a67ad27c3ee83c1
Type fulltextMimetype application/pdf

By organisation
Department of Chemistry
Organic Chemistry

Search outside of DiVA

GoogleGoogle Scholar
Total: 5598 downloads
The number of downloads is the sum of all downloads of full texts. It may include eg previous versions that are now no longer available

isbn
urn-nbn

Altmetric score

isbn
urn-nbn
Total: 1310 hits
CiteExportLink to record
Permanent link

Direct link
Cite
Citation style
  • apa
  • ieee
  • modern-language-association-8th-edition
  • vancouver
  • Other style
More styles
Language
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Other locale
More languages
Output format
  • html
  • text
  • asciidoc
  • rtf