Change search
ReferencesLink to record
Permanent link

Direct link
Palladium(II)-Catalysed Heck and Addition Reactions: Exploring Decarboxylative and Desulfitative Processes
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Medicinal Chemistry, Organic Pharmaceutical Chemistry.ORCID iD: 0000-0002-8014-5757
2016 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

Palladium complexes have the ability to catalyse cross-coupling of two organic moieties through the formation of transient metal-carbon bonds, thus bringing them closer to each other to facilitate the formation of a new bond. Palladium-catalysed coupling reactions are one of the most important carbon-carbon forming reactions available to organic chemists and many of these reactions rely on the reactivity of aryl-palladium complexes. The investigation of new aryl-palladium precursors is thus of great interest, especially as more sustainable and economic methods can be developed.

This thesis describes the use of carboxylic acids and sodium arylsulfinates as such new arylating agents. Protocols for microwave-assisted palladium(II)-catalysed decarboxylative synthesis of electron-rich styrenes and 1,1-diarylethenes were developed. However, these transformations had very limited substrate scopes which prompted the investigation of sodium arylsulfinates as alternative arylating agents. These substrates were employed in the microwave-assisted palladium(II)-catalysed desulfitative addition to nitriles, and the substrate scope was demonstrated by combining a wide array of sodium arylsulfinates and nitriles to yield the corresponding aryl ketones. The application of the desulfitative reaction in a continuous flow setup was demonstrated, and aluminium oxide was identified as safe alternative to borosilicate glass as a reactor material. The mechanisms of the decarboxylative and desulfitative transformations were investigated by density functional theory (DFT) calculations. The desulfitative reaction was also investigated by direct electrospray ionization mass spectrometry (ESI-MS), providing further mechanistic insight. Finally, a protocol for the safe and convenient synthesis of a wide range of sodium arylsulfinates was developed.

Place, publisher, year, edition, pages
Uppsala: Acta Universitatis Upsaliensis, 2016. , 100 p.
Series
Digital Comprehensive Summaries of Uppsala Dissertations from the Faculty of Pharmacy, ISSN 1651-6192 ; 221
Keyword [en]
Palladium, catalysis, palladium(II) catalysis, synthesis, Heck, carboxylic acid, sulfinic acid, sodium sulfinate, nitrile, styrene, ketone, aryl ketone, electrospray ionization mass spectrometry, density functional theory, microwave heating, continuous flow
National Category
Organic Chemistry
Research subject
Chemistry with specialization in Organic Chemistry
Identifiers
URN: urn:nbn:se:uu:diva-304746ISBN: 978-91-554-9717-0OAI: oai:DiVA.org:uu-304746DiVA: diva2:1033751
Public defence
2016-11-25, B21, BMC, Husargatan 3, Uppsala, 09:15 (English)
Opponent
Supervisors
Available from: 2016-11-04 Created: 2016-10-10 Last updated: 2016-11-16
List of papers
1. Experimental and Theoretical Investigation of Palladium(II)-Catalyzed Decarboxylative Synthesis of Electron-Rich Styrenes and 1,1-Diarylethenes
Open this publication in new window or tab >>Experimental and Theoretical Investigation of Palladium(II)-Catalyzed Decarboxylative Synthesis of Electron-Rich Styrenes and 1,1-Diarylethenes
Show others...
(English)Manuscript (preprint) (Other academic)
National Category
Organic Chemistry
Research subject
Organic Chemistry
Identifiers
urn:nbn:se:uu:diva-304720 (URN)
Available from: 2016-10-08 Created: 2016-10-08 Last updated: 2016-10-10
2. Palladium(II)-Catalyzed Desulfitative Synthesis of Aryl Ketones from Sodium Arylsulfinates and Nitriles: Scope, Limitations, and Mechanistic Studies
Open this publication in new window or tab >>Palladium(II)-Catalyzed Desulfitative Synthesis of Aryl Ketones from Sodium Arylsulfinates and Nitriles: Scope, Limitations, and Mechanistic Studies
Show others...
2014 (English)In: Journal of Organic Chemistry, ISSN 0022-3263, E-ISSN 1520-6904, Vol. 79, no 24, 12018-12032 p.Article in journal (Refereed) Published
Abstract [en]

A fast and efficient protocol for the palladium(II)-catalyzed production of aryl ketones from sodium arylsulfinates and various organic nitriles under controlled microwave irradiation has been developed. The wide scope of the reaction has been demonstrated by combining 14 sodium arylsulfinates and 21 nitriles to give 55 examples of aryl ketones. One additional example illustrated that, through the choice of the nitrile reactant, benzofurans are also accessible. The reaction mechanism was investigated by electrospray ionization mass spectrometry and DFT calculations. The desulfitative synthesis of aryl ketones from nitriles was also compared to the corresponding transformation starting from benzoic acids. Comparison of the energy profiles indicates that the free energy requirement for decarboxylation of 2,6-dimethoxybenzoic acid and especially benzoic acid is higher than the corresponding desulfitative process for generating the key aryl palladium intermediate. The palladium(II) intermediates detected by ESI-MS and the DFT calculations provide a detailed understanding of the catalytic cycle.

National Category
Chemical Sciences
Identifiers
urn:nbn:se:uu:diva-240562 (URN)10.1021/jo501875n (DOI)000346759500020 ()25295849 (PubMedID)
Available from: 2015-01-08 Created: 2015-01-07 Last updated: 2016-10-10Bibliographically approved
3. Microwave Heated Continuous Flow Palladium(II)-Catalyzed Desulfitative Synthesis of Aryl Ketones
Open this publication in new window or tab >>Microwave Heated Continuous Flow Palladium(II)-Catalyzed Desulfitative Synthesis of Aryl Ketones
2016 (English)In: Organic Process Research & Development, ISSN 1083-6160, E-ISSN 1520-586XArticle in journal (Refereed) Submitted
Place, publisher, year, edition, pages
American Chemical Society (ACS), 2016
National Category
Organic Chemistry
Identifiers
urn:nbn:se:uu:diva-304719 (URN)
Available from: 2016-10-08 Created: 2016-10-08 Last updated: 2016-10-10
4. Synthesis of sodium aryl sulfinates from aryl bromides employing 1,4-diazabicyclo[2.2.2]octane bis(sulfur dioxide) adduct (DABSO) as a bench-stable, gas-free alternative to SO2
Open this publication in new window or tab >>Synthesis of sodium aryl sulfinates from aryl bromides employing 1,4-diazabicyclo[2.2.2]octane bis(sulfur dioxide) adduct (DABSO) as a bench-stable, gas-free alternative to SO2
2016 (English)In: Tetrahedron Letters, ISSN 0040-4039, E-ISSN 1359-8562, Vol. 57, no 5, 533-536 p.Article in journal (Refereed) Published
Abstract [en]

Abstract A convenient two-step protocol for the synthesis of sodium aryl sulfinates from aryl bromides and the SO2 surrogate 1,4-diazabicyclo[2.2.2]octane bis(sulfur dioxide) adduct (DABSO) has been developed. A wide range of aryl bromides with respect to electronic properties were employed to give the corresponding sodium arylsulfinates in good to excellent yields. The protocol is especially efficient for electron poor aryl bromides which are often difficult to prepare using existing methods.

Keyword
Sodium sulfinate, Sulfur dioxide surrogate, DABSO
National Category
Organic Chemistry
Identifiers
urn:nbn:se:uu:diva-276924 (URN)10.1016/j.tetlet.2015.12.073 (DOI)000369557300007 ()
Funder
Knut and Alice Wallenberg Foundation
Available from: 2016-02-16 Created: 2016-02-16 Last updated: 2016-10-10Bibliographically approved

Open Access in DiVA

fulltext(2792 kB)76 downloads
File information
File name FULLTEXT01.pdfFile size 2792 kBChecksum SHA-512
4c85f06435fe43dbc4c005eaab1815acfcc3575709df4472fa0155bdb281facf66d632506b7a62451243590f6f40df842d7a2141fd380134da1a9edf636f021e
Type fulltextMimetype application/pdf
Buy this publication >>

Search in DiVA

By author/editor
Skillinghaug, Bobo
By organisation
Organic Pharmaceutical Chemistry
Organic Chemistry

Search outside of DiVA

GoogleGoogle Scholar
Total: 76 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

Total: 291 hits
ReferencesLink to record
Permanent link

Direct link