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Åkerbladh, Linda
Publications (9 of 9) Show all publications
Åkerbladh, L., Odell, L. R. & Larhed, M. (2019). Palladium-Catalyzed Molybdenum Hexacarbonyl-Mediated Gas-Free Carbonylative Reactions. Synlett: Accounts and Rapid Communications in Synthetic Organic Chemistry, 30(2), 141-155
Open this publication in new window or tab >>Palladium-Catalyzed Molybdenum Hexacarbonyl-Mediated Gas-Free Carbonylative Reactions
2019 (English)In: Synlett: Accounts and Rapid Communications in Synthetic Organic Chemistry, ISSN 0936-5214, E-ISSN 1437-2096, Vol. 30, no 2, p. 141-155Article in journal (Refereed) Published
Abstract [en]

This account summarizes Pd(0)-catalyzed Mo(CO) 6-mediated gas-free carbonylative reactions published in the period October 2011 to May 2018. Presented reactions include inter-and intramolecular carbonylations, carbonylative cross-couplings, and carbonylative multicomponent reactions using Mo(CO) 6 as a solid source of CO. The presented methodologies were developed mainly for small-scale applications, avoiding the problematic use of gaseous CO in a standard laboratory. In most cases, the reported Mo(CO) 6-mediated carbonylations were conducted in sealed vials or by using two-chamber solutions. 1 Introduction 2 Recent Developments 2.1 New CO Sources 2.2 Two-Chamber System for ex Situ CO Generation 2.3 Multicomponent Carbonylations 3 Carbonylations with N and O Nucleophiles 4 Carbonylative Cross-Coupling Reactions with Organometallics 5 Carbonylative Cascade Reactions 6 Carbonylative Cascade, Multistep Reactions 7 Summary and Outlook

Place, publisher, year, edition, pages
GEORG THIEME VERLAG KG, 2019
Keywords
carbonylation, molybdenum, multicomponent reactions, palladium, catalysis
National Category
Medicinal Chemistry
Identifiers
urn:nbn:se:uu:diva-375233 (URN)10.1055/s-0037-1610294 (DOI)000455224600005 ()
Funder
Knut and Alice Wallenberg Foundation
Available from: 2019-01-29 Created: 2019-01-29 Last updated: 2019-01-29Bibliographically approved
Odell, L. R., Åkerbladh, L., Schembri, L. S., Nordeman, P., Roslin, S. & Eriksson, J. (2018). Carbonylations beyond aryl-X: Development of new multicomponent reactions. Paper presented at 255th National Meeting and Exposition of the American-Chemical-Society (ACS) - Nexus of Food, Energy, and Water, MAR 18-22, 2018, New Orleans, LA. Abstract of Papers of the American Chemical Society, 255
Open this publication in new window or tab >>Carbonylations beyond aryl-X: Development of new multicomponent reactions
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2018 (English)In: Abstract of Papers of the American Chemical Society, ISSN 0065-7727, Vol. 255Article in journal, Meeting abstract (Other academic) Published
National Category
Organic Chemistry
Identifiers
urn:nbn:se:uu:diva-367232 (URN)000435539901514 ()
Conference
255th National Meeting and Exposition of the American-Chemical-Society (ACS) - Nexus of Food, Energy, and Water, MAR 18-22, 2018, New Orleans, LA
Available from: 2018-12-06 Created: 2018-12-06 Last updated: 2018-12-06Bibliographically approved
Åkerbladh, L. (2017). Palladium(0)-Catalysed Carbonylative Multicomponent Reactions: Synthesis of Heterocycles and the Application of Quinolinyl Pyrimidines as Enzyme Inhibitors. (Doctoral dissertation). Uppsala: Acta Universitatis Upsaliensis
Open this publication in new window or tab >>Palladium(0)-Catalysed Carbonylative Multicomponent Reactions: Synthesis of Heterocycles and the Application of Quinolinyl Pyrimidines as Enzyme Inhibitors
2017 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

Palladium-catalysed carbonylative multicomponent reactions have proven useful for the synthesis of structurally diverse compounds. Carbon monoxide serves as an atom-efficient, one-carbon building block, which allows for further structural elaboration of the carbonyl compound. By varying the components of the carbonylative multicomponent reaction, considerable product diversity can readily be attained. However, due to the reluctance to use toxic CO gas, considerable efforts have been directed at exploring non-gaseous approaches. The work described in this thesis has mainly focused on the development of palladium(0)-catalysed, carbonylative multicomponent synthetic methodology, using the non-gaseous CO source molybdenum hexacarbonyl, in the synthesis of heterocycles and other biologically relevant functional groups.

The first part of this work describes the development of a non-gaseous carbonylative Sonogashira cross-coupling of bifunctional ortho-iodoanilines and terminal alkynes. Where 4-quinolones were synthesised via a carbonylation/cyclisation sequence. Using a similar synthetic strategy, three different N-cyanobenzamide intermediates were prepared by palladium-catalysed carbonylative couplings of various aryl halides and bromides and cyanamide. The formed intermediates provided a basis for further chemical transformations. First, ortho-iodoanilines were carbonylatively coupled with cyanamide and subsequently cyclised to yield heterocyclic 2-aminoquinazolinones. Next, building on those findings, the same synthetic strategy was applied to ortho-halophenols to provide a highly convenient domino carbonylation/cyclisation method for the preparation of benzoxazinones. The developed method was used to evaluate the efficiency of various non-gaseous CO sources. Third, the palladium-catalysed carbonylative synthesis of N-cyanobenzamides, was used to produce biologically relevant N-acylguanidines with considerable product diversity. Finally, one of the developed carbonylative methodologies was used in the preparation of potential NDH-2 inhibitors based on a quinolinyl pyrimidine scaffold. The prepared compounds were biologically evaluated in terms of inhibition of oxidoreductase NDH-2 and antibacterial activity on Gram-negative bacteria, S. aureus and Mtb. The biological evaluation revealed that some of the quinolinyl pyrimidines exerted inhibitory activity on the NDH-2 enzyme and possessed antibacterial properties.

The work described in this thesis has been devoted to the development of non-gaseous one-pot, multicomponent carbonylation/cyclisation and carbonylation/amination reactions. The described methods offer highly attractive synthetic strategies that can be of great value to synthetic and medicinal chemists.

Place, publisher, year, edition, pages
Uppsala: Acta Universitatis Upsaliensis, 2017. p. 86
Series
Digital Comprehensive Summaries of Uppsala Dissertations from the Faculty of Pharmacy, ISSN 1651-6192 ; 237
Keywords
Palladium catalysis, Carbonylation, Multicomponent reactions, Domino reactions, Heterocycles, 4-Quinolones, 2-Aminoquinazolinones, Benzoxazinones, N-Acylguanidines, Type II NADH dehydrogenase, NDH-2
National Category
Organic Chemistry Medicinal Chemistry
Identifiers
urn:nbn:se:uu:diva-329970 (URN)978-91-513-0083-2 (ISBN)
Public defence
2017-11-10, B41, BMC, Husargatan 3, Uppsala, 09:15 (English)
Opponent
Supervisors
Available from: 2017-10-20 Created: 2017-09-24 Last updated: 2018-01-13
Åkerbladh, L., Schembri, L. S., Larhed, M. & Odell, L. R. (2017). Palladium(0)-Catalyzed Carbonylative One-Pot Synthesis of N-Acylguanidines. Journal of Organic Chemistry, 82(23), 12520-12529
Open this publication in new window or tab >>Palladium(0)-Catalyzed Carbonylative One-Pot Synthesis of N-Acylguanidines
2017 (English)In: Journal of Organic Chemistry, ISSN 0022-3263, E-ISSN 1520-6904, Vol. 82, no 23, p. 12520-12529Article in journal (Refereed) Published
Abstract [en]

A convenient synthetic strategy toward N-acylguanidines via a sequential one-pot multicomponent carbonylation/amination reaction has been developed. The compounds were readily obtained via an N-cyanobenzamide intermediate formed from the Pd(0)-catalyzed carbonylative coupling of cyanamide and aryl iodides or bromides. Subsequent amination with a large variety of amines provided the final N-acylguanidines, with the overall formation of one C-C and two C-N bonds, in moderate to excellent yields. The substrate scope was found to be wide and the methodology was used to produce over 50 compounds, including 29 novel molecules. Furthermore, three separate nitrogen-containing heterocycles were prepared from the N-acylguanidines synthesized using the developed multicomponent, carbonylative method.

National Category
Organic Chemistry
Identifiers
urn:nbn:se:uu:diva-343509 (URN)10.1021/acs.joc.7b02294 (DOI)000417342300056 ()29027801 (PubMedID)
Available from: 2018-02-27 Created: 2018-02-27 Last updated: 2018-03-08Bibliographically approved
Åkerbladh, L., Chow, S. Y., Odell, L. R. & Larhed, M. (2017). Synthesis of 4H-Benzo[e][1,3]oxazin-4-ones by a Carbonylation-Cyclization Domino Reaction of ortho-Halophenols and Cyanamide. ChemistryOpen, 6(5), 620-628
Open this publication in new window or tab >>Synthesis of 4H-Benzo[e][1,3]oxazin-4-ones by a Carbonylation-Cyclization Domino Reaction of ortho-Halophenols and Cyanamide
2017 (English)In: ChemistryOpen, ISSN 2191-1363, Vol. 6, no 5, p. 620-628Article in journal (Refereed) Published
Abstract [en]

A mild and convenient one-step preparation of 4H-1,3-benzoxazin-4-ones by a domino carbonylation-cyclization process is developed. Readily available ortho-iodophenols are subjected to palladium-catalyzed carbonylative coupling with Mo(CO)(6) and cyanamide, followed by a spontaneous, intramolecular cyclization to afford 4H-1,3-benzaxazin-4-ones in moderate to excellent yields. Furthermore, the scope of the reaction is ex tended to include challenging orthobromophenols. Finally, to highlight the versatility of the developed method, Mo(CO), is successfully replaced with a wide array of CO-releasing reagents, such as oxalyl chloride, phenyl formate, 9-methylfluorene-9-carbonyl chloride, and formic acid, making this an appealing strategy for the synthesis of 4H-benzo[e][1,3]oxazin-4-ones.

National Category
Organic Chemistry
Identifiers
urn:nbn:se:uu:diva-329967 (URN)10.1002/open.201700130 (DOI)000413038400003 ()29046856 (PubMedID)
Available from: 2017-09-24 Created: 2017-09-24 Last updated: 2018-02-05Bibliographically approved
(2016). Mild and Low-Pressure fac-Ir(ppy)3-Mediated Radical Aminocarbonylation of Unactivated Alkyl Iodides through Visible-Light Photoredox Catalysis. Chemistry - A European Journal, 22(27), 9033
Open this publication in new window or tab >>Mild and Low-Pressure fac-Ir(ppy)3-Mediated Radical Aminocarbonylation of Unactivated Alkyl Iodides through Visible-Light Photoredox Catalysis
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2016 (English)In: Chemistry - A European Journal, ISSN 0947-6539, E-ISSN 1521-3765, Vol. 22, no 27, p. 9033-Article in journal, Editorial material (Other academic) Published
Abstract [en]

Iridium stands at the center of a vortex of electrons that are transferred to and from the surrounding reaction components in this radical aminocarbonylation method. The combination of visible-light irradiation and low-pressure ex situ carbon monoxide generation makes this an attractive and operationally simple approach for preparing β-hydride-containing alkyl amides. Additional cover art acknowledgements: Bobo Skillinghaug and Johan Sjöstedt. More information can be found in the Full Paper by L. R. Odell et al. on page 9155 ff.

Keywords
amides, carbonylation, photocatalysis, radical reactions
National Category
Organic Chemistry
Research subject
Chemistry with specialization in Organic Chemistry
Identifiers
urn:nbn:se:uu:diva-303997 (URN)10.1002/chem.201602396 (DOI)2-s2.0-84977495975 (Scopus ID)
Note

Cover profile / cover page

Available from: 2016-09-28 Created: 2016-09-28 Last updated: 2017-11-21Bibliographically approved
Åkerbladh, L. & Odell, L. R. (2016). Synthesis of 2-Aminoquinazolinones via Carbonylative Coupling of ortho-lodoanilines and Cyanamide. Journal of Organic Chemistry, 81(7), 2966-2973
Open this publication in new window or tab >>Synthesis of 2-Aminoquinazolinones via Carbonylative Coupling of ortho-lodoanilines and Cyanamide
2016 (English)In: Journal of Organic Chemistry, ISSN 0022-3263, E-ISSN 1520-6904, Vol. 81, no 7, p. 2966-2973Article in journal (Refereed) Published
Abstract [en]

Herein, we describe a convenient and efficient synthesis of 2-aminoquinazolin-4(3H)-ones and N1-substituted 2-aminoquinazolin-4(1H)-ones by a domino carbonylation/cyclization process. The reaction proceeds via carbonylative coupling of readily available ortho-iodoanilines with cyanamide followed by in situ ring closure of an N-cyanobenzamide intermediate. The products were easily isolated by precipitation in moderate to excellent yields for a wide range of substrates, making this a highly attractive method for the synthesis of 2-aminoquinazolinones.

National Category
Organic Chemistry
Identifiers
urn:nbn:se:uu:diva-295556 (URN)10.1021/acs.joc.6b00249 (DOI)000373520200028 ()26967689 (PubMedID)
Available from: 2016-06-22 Created: 2016-06-08 Last updated: 2017-11-28Bibliographically approved
Russo, F., Gising, J., Åkerbladh, L., Roos, A. K., Naworyta, A., Mowbray, S. L., . . . Larhed, M. (2015). Optimization and Evaluation of 5-Styryl-Oxathiazol-2-one Mycobacterium tuberculosis Proteasome Inhibitors as Potential Antitubercular Agents. ChemistryOpen, 4(3), 342-362
Open this publication in new window or tab >>Optimization and Evaluation of 5-Styryl-Oxathiazol-2-one Mycobacterium tuberculosis Proteasome Inhibitors as Potential Antitubercular Agents
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2015 (English)In: ChemistryOpen, ISSN 2191-1363, Vol. 4, no 3, p. 342-362Article in journal (Refereed) Published
Abstract [en]

This is the first report of 5-styryl-oxathiazol-2-ones as inhibitors of the Mycobacterium tuberculosis (Mtb) proteasome. As part of the study, the structure-activity relationship of oxathiazolones as Mtb proteasome inhibitors has been investigated. Furthermore, the prepared compounds displayed a good selectivity profile for Mtb compared to the human proteasome. The 5-styryl-oxathiazol-2-one inhibitors identified showed little activity against replicating Mtb, but were rapidly bactericidal against nonreplicating bacteria. (E)-5-(4-Chlorostyryl)-1,3,4-oxathiazol-2-one) was most effective, reducing the colony-forming units (CFU)/mL below the detection limit in only seven days at all concentrations tested. The results suggest that this new class of Mtb proteasome inhibitors has the potential to be further developed into novel antitubercular agents for synergistic combination therapies with existing drugs.

Keywords
antitubercular agents, 5-styryl-oxathiazolones, Mtb proteasome inhibitor, Mycobacterium tuberculosis, nonreplicating Mtb, rapid bactericidal activity
National Category
Chemical Sciences
Identifiers
urn:nbn:se:uu:diva-258781 (URN)10.1002/open.201500001 (DOI)000356820900015 ()
Funder
VINNOVA
Available from: 2015-07-20 Created: 2015-07-20 Last updated: 2017-12-04Bibliographically approved
Åkerbladh, L., Nordeman, P., Wejdemar, M., Odell, L. R. & Larhed, M. (2015). Synthesis of 4-Quinolones via a Carbonylative Sonogashira Cross-Coupling Using Molybdenum Hexacarbonyl as a CO Source. Journal of Organic Chemistry, 80(3), 1464-1471
Open this publication in new window or tab >>Synthesis of 4-Quinolones via a Carbonylative Sonogashira Cross-Coupling Using Molybdenum Hexacarbonyl as a CO Source
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2015 (English)In: Journal of Organic Chemistry, ISSN 0022-3263, E-ISSN 1520-6904, Vol. 80, no 3, p. 1464-1471Article in journal (Refereed) Published
Abstract [en]

A palladium-catalyzed CO gas-free carbonylative Sonogashira/cyclization sequence for the preparation of functionalized 4-quinolones from 2-iodoanilines and alkynes via two different protocols is described. The first method (A) yields the cyclized products after only 20 min of microwave (MW) heating at 120 degrees C. The second method (B) is a gas-free one-pot two-step sequence which runs at room temperature, allowing the use of sensitive substituents (e.g., nitro and bromide groups). For both protocols, molybdenum hexacarbonyl was used as a solid source of CO.

National Category
Chemical Sciences
Identifiers
urn:nbn:se:uu:diva-249019 (URN)10.1021/jo502400h (DOI)000349934600019 ()25575042 (PubMedID)
Available from: 2015-04-24 Created: 2015-04-10 Last updated: 2017-12-04Bibliographically approved
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