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Palladium-Catalyzed Carbonylation and Arylation Reactions
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Medicinal Chemistry, Organic Pharmaceutical Chemistry.
2012 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

Palladium-catalyzed reactions have found widespread use in contemporary organic chemistry due to their impressive range of functional group tolerance and high chemo- and regioselectivity. The pioneering contributions to the development of the Pd-catalyzed C-C bond forming cross-coupling reaction were rewarded with the Nobel Prize in Chemistry in 2010. Today, this is a rapidly growing field, and the development of novel methods, as well as the theoretical understanding of the various processes involved are of immense importance for continued progress in this field.

The aim of the work presented in this thesis was to develop novel palladium(0)- and palladium(II)-catalyzed reactions. The work involved in achieving this aim led to the development of a Mo(CO)6-mediated carbonylative Stille cross coupling reaction for the preparation of various deoxybenzoins. The protocol utilized convenient gas-free conditions to facilitate the carbonylative coupling of benzyl bromides and chlorides with aryl and heteroaryl stannanes. Mo(CO)6-assisted conditions were then used in the development of a general protocol suitable for the aminocarbonylation of aryl triflates. Both electron-poor and electron-rich triflates were coupled with primary, secondary and aryl amines. In addition, DMAP was found to be a beneficial additive when using sterically hindered or poorly nucleophilic amines.

An efficient and convenient method for the synthesis of styrenes from arylboranes was developed, employing the relatively inexpensive vinyl acetate as the ethene source under Pd(II)-catalyzed conditions. The reaction mechanism was studied using ESI-MS, and a plausible catalytic cycle was proposed.

A method for the oxidative Heck reaction employing aryltrifluoroborates and aryl MIDA boronates was also developed. Electron-rich and electron-poor olefins were regioselectively arylated under microwave-assisted conditions. Various arylboron species were identified in an ongoing reaction using ESI-MS.   

Further investigations led to the development of a direct method for the synthesis of arylamidines from aryltrifluoroborates and cyanamides. Under Pd(II)-catalyzed conditions it was possible to insert the aryl into primary, secondary and tertiary cyanamides.

Finally, a desulfitative method for the synthesis of aryl ketones was developed. A variety of aryl sulfinates were effectively inserted into alkyl- and aryl nitriles. The mechanism was further investigated using ESI-MS and a plausible catalytic cycle was proposed.

Place, publisher, year, edition, pages
Uppsala: Acta Universitatis Upsaliensis , 2012. , 81 p.
Series
Digital Comprehensive Summaries of Uppsala Dissertations from the Faculty of Pharmacy, ISSN 1651-6192 ; 155
Keyword [en]
palladium, carbonylation, styrene, amidine, aryl ketones, aryl sulfinates, ESI-MS, aryltrifluoroborates
National Category
Medicinal Chemistry
Research subject
Organic Pharmaceutical Chemistry
Identifiers
URN: urn:nbn:se:uu:diva-167720ISBN: 978-91-554-8267-1 (print)OAI: oai:DiVA.org:uu-167720DiVA: diva2:487817
Public defence
2012-03-16, B:41, BMC, Husargatan 3, Uppsala, 09:15 (English)
Opponent
Supervisors
Available from: 2012-02-21 Created: 2012-01-31 Last updated: 2012-03-01
List of papers
1. Deoxybenzoins from Stille carbonylative cross-couplings using molybdenum hexacarbonyl
Open this publication in new window or tab >>Deoxybenzoins from Stille carbonylative cross-couplings using molybdenum hexacarbonyl
2010 (English)In: Tetrahedron Letters, ISSN 0040-4039, E-ISSN 1359-8562, Vol. 51, no 52, 6886-6889 p.Article in journal (Refereed) Published
Abstract [en]

Stille-type carbonylative cross-couplings, employing palladium catalysis and Mo(CO)6 as the carbon monoxide carrier, were used for the preparation of deoxybenzoins. Straightforward transformations were conveniently performed in closed vessels at 100 C, providing the products in good yields. Benzyl bromides and chlorides were used as coupling partners with aryl and heteroaryl stannanes. This mild three-component carbonylation employs the destabilizing agent DBU to promote smooth release of carbon monoxide from Mo(CO)6, which made this protocol operationally simple and minimized the formation of Stille diarylmethane products.

Keyword
Stille, molybdenum hexacarbonyl, deoxybenzoins, palladium
National Category
Organic Chemistry
Identifiers
urn:nbn:se:uu:diva-167715 (URN)10.1016/j.tetlet.2010.10.115 (DOI)000285670400023 ()
Available from: 2012-01-31 Created: 2012-01-31 Last updated: 2017-12-08Bibliographically approved
2. Microwave-promoted aminocarbonylation of aryl triflates using Mo(CO)(6) as a solid CO source
Open this publication in new window or tab >>Microwave-promoted aminocarbonylation of aryl triflates using Mo(CO)(6) as a solid CO source
2008 (English)In: Tetrahedron Letters, ISSN 0040-4039, E-ISSN 1359-8562, Vol. 49, no 42, 6115-6118 p.Article in journal (Refereed) Published
Abstract [en]

Palladium-catalyzed carbonylations of aryl triflates with a range of nucleophiles using Mo(CO)(6) as a solid CO source were explored. The reactions proceeded smoothly providing moderate to good yields of the corresponding aryl amides, esters, or acylsulfonamides after only 20 min of microwave irradiation. The acyl transfer reagent 4-dimethylaminopyridine was found to promote some of the more difficult transformations. (C) 2008 Elsevier Ltd. All rights reserved.

Keyword
carbonylation, microwave, palladium, aryl triflate, DMAP
National Category
Chemical Sciences
Identifiers
urn:nbn:se:uu:diva-104379 (URN)10.1016/j.tetlet.2008.08.014 (DOI)000259883800024 ()0040-4039 (ISBN)
Available from: 2009-05-28 Created: 2009-05-28 Last updated: 2017-12-13Bibliographically approved
3. Synthesis of styrenes by palladium(II)-catalyzed vinylation of arylboronic acids and aryltrifluoroborates by using vinyl acetate
Open this publication in new window or tab >>Synthesis of styrenes by palladium(II)-catalyzed vinylation of arylboronic acids and aryltrifluoroborates by using vinyl acetate
Show others...
2009 (English)In: Chemistry - A European Journal, ISSN 0947-6539, E-ISSN 1521-3765, Vol. 15, no 18, 4630-4636 p.Article in journal (Refereed) Published
Abstract [en]

Reactions of aromatic and heteroaromatic boronic acids or aryltrifluoroborate salts with vinyl acetate in the presence of a palladium(II) catalyst give the corresponding styrenes in good yields. This Heck reaction proceeds with microwave heating in less than 30 min at 140 degrees C in the absence of base and tolerates a variety of substituents. No palladium reoxidant is needed and the vinylation is performed under non-inert conditions. Mass spectrometry (electrospray ionization mass spectrometry (ESIMS) and tandem mass spectrometry   (MS/MS)) was used to identify cationic palladium-containing complexes in ongoing reactions. The key intermediates that have been detected, together with experiments that used deuterated vinyl acetate, support the existence of catalytically active palladium hydride species, and that it is the arylation of ethylene, not vinyl acetate, which   generates the styrene product. The mechanism of the reaction is discussed in terms of the palladium(II) intermediates mentioned above.

Keyword
Heck reaction, mass spectrometry, mechanistic studies, palladium, styrene
National Category
Chemical Sciences
Identifiers
urn:nbn:se:uu:diva-102918 (URN)10.1002/chem.200802744 (DOI)000265955200018 ()19274694 (PubMedID)
Available from: 2009-05-13 Created: 2009-05-12 Last updated: 2017-12-13Bibliographically approved
4. Oxidative Heck Reactions Using Aryltrifluoroborates and Aryl N-Methyliminodiacetic Acid (MIDA) Boronates
Open this publication in new window or tab >>Oxidative Heck Reactions Using Aryltrifluoroborates and Aryl N-Methyliminodiacetic Acid (MIDA) Boronates
Show others...
2012 (English)In: ChemistryOpen, ISSN 2191-1363, Vol. 1, no 3, 140-146 p.Article in journal (Refereed) Published
Place, publisher, year, edition, pages
Weinheim: Wiley-VCH Verlagsgesellschaft, 2012
Keyword
Heck reactions, N-methyliminodiacetic acid (MIDA), oxidative reactions, palladium complexes, trifluoroborate
National Category
Organic Chemistry
Research subject
Chemistry with specialization in Organic Chemistry
Identifiers
urn:nbn:se:uu:diva-167718 (URN)10.1002/open.201200007 (DOI)000328607400004 ()
Funder
Swedish Research Council
Available from: 2012-01-31 Created: 2012-01-31 Last updated: 2017-12-08Bibliographically approved
5. Direct Palladium(II)-Catalyzed Synthesis of Arylamidines from Aryltrifluoroborates
Open this publication in new window or tab >>Direct Palladium(II)-Catalyzed Synthesis of Arylamidines from Aryltrifluoroborates
Show others...
2012 (English)In: Organic Letters, ISSN 1523-7060, E-ISSN 1523-7052, Vol. 14, no 9, 2394-2397 p.Article in journal (Refereed) Published
Abstract [en]

A fast and convenient synthesis of arylamidines starting from readily available potassium aryltrifluoroborates and cyanamides is reported. The coupling was achieved by Pd(II)-catalysis in a one step 20 min microwave protocol using Pd(O2CCF3), 6-methyl-2,2'-bipyridyl, TFA, and MeOH, providing the corresponding arylamidines in moderate to excellent yields.

National Category
Organic Chemistry
Identifiers
urn:nbn:se:uu:diva-167719 (URN)10.1021/ol300813c (DOI)000303492200052 ()
Available from: 2012-01-31 Created: 2012-01-31 Last updated: 2017-12-08Bibliographically approved
6. Microwave-Assisted Palladium(II)-Catalyzed Synthesis of Aryl Ketones from Aryl Sulfinates and Direct ESI-MS Studies Thereof
Open this publication in new window or tab >>Microwave-Assisted Palladium(II)-Catalyzed Synthesis of Aryl Ketones from Aryl Sulfinates and Direct ESI-MS Studies Thereof
2011 (English)In: ACS Catalysis, ISSN 2155-5435, Vol. 1, no 11, 1455-1459 p.Article in journal (Refereed) Published
Abstract [en]

A fast palladium(II)-catalyzed and microwave-promoted procedure using 6-methyl-2,2'-bipyridyl as ligand to synthesize aryl ketones from aryl sulfinates and nitriles is described. More importantly, the first detailed investigation of the reaction mechanism using direct ESI-MS studies is reported.

Keyword
palladium, catalysis, desulfination, aryl sulfinates, aryl ketones, nitriles, ESI-MS, microwave
National Category
Chemical Sciences
Identifiers
urn:nbn:se:uu:diva-162466 (URN)10.1021/cs200428u (DOI)000296598000002 ()
Available from: 2011-11-30 Created: 2011-11-30 Last updated: 2012-06-01Bibliographically approved

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