TRANSITION METAL CATALYZED CROSS-COUPLINGS OF ALKYL SULFONE ELECTROPHILES

dc.contributor.authorAriki, Zacharyen
dc.contributor.departmentChemistryen
dc.contributor.supervisorCrudden, Cathleen
dc.date.accessioned2021-02-01T21:58:50Z
dc.date.available2021-02-01T21:58:50Z
dc.degree.grantorQueen's University at Kingstonen
dc.description.abstractSulfones are an important class of organic molecules that can participate in a wide variety of synthetic transformations. For this reason, they have been described as chemical chameleons. While their use as Csp2 electrophiles in cross-coupling dates to the early 1970’s, their potential as competent Csp3 electrophiles has not been recognized until recently. Our group has made significant contributions to the development of new cross-coupling methodologies utilizing alkyl sulfones as electrophiles. This thesis describes the use of alkyl sulfones as electrophiles in both nickel and palladium catalyzed cross-coupling reactions. First, we developed a nickel-catalyzed Suzuki–Miyaura cross-coupling of π-extended tertiary benzylic and allylic sulfones with arylboroxines. A variety of tertiary sulfones were reacted to afford quaternary products in good yields and we identified a unique phosphine ligand capable of promoting the challenging cross-coupling reaction. The method enabled the concise synthesis of a biologically active molecule. We then adapted and extended the nickel-catalyzed system to the cross-coupling of simple tertiary benzylic sulfones using olefins as removable directing groups. Several dialkydiarylmethanes were prepared in good yields and we revealed that the mechanism likely involves an η2-nickel coordination complex with the olefin, which facilitates oxidative addition. Following cross-coupling, the olefin could be cleaved to introduce new functionalities. Next, we developed a nickel-catalyzed Kumada cross-coupling of cyclic alkyl sulfones with aryl Grignard nucleophiles. Uniquely, the sulfinate leaving group was retained following ring-opening cross-coupling and it served as a handle for further functionalization. Overall, the methodology provided access to doubly functionalized products in a one-pot procedure. Finally, we developed a palladium-catalyzed Suzuki-Miyaura cross-coupling of α-fluorinated benzylic triflones with arylboronic acids. The method afforded a variety of mono- and difluorinated diarylmethanes and we demonstrated that both mono- and difluorinated benzylic triflones could be desulfonylated to afford the corresponding α-fluoromethylarenes. Because α-fluoromethylarenes are important substructures in pharmaceuticals and agrochemicals, we utilized our methodology to prepare several fluorinated analogues and derivatives of biologically active compounds.en
dc.description.degreePhDen
dc.identifier.urihttp://hdl.handle.net/1974/28683
dc.language.isoengen
dc.relation.ispartofseriesCanadian thesesen
dc.rightsQueen's University's Thesis/Dissertation Non-Exclusive License for Deposit to QSpace and Library and Archives Canadaen
dc.rightsProQuest PhD and Master's Theses International Dissemination Agreementen
dc.rightsIntellectual Property Guidelines at Queen's Universityen
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dc.rightsThis publication is made available by the authority of the copyright owner solely for the purpose of private study and research and may not be copied or reproduced except as permitted by the copyright laws without written authority from the copyright owner.en
dc.rightsCC0 1.0 Universal*
dc.rights.urihttp://creativecommons.org/publicdomain/zero/1.0/*
dc.subjectCross-couplingen
dc.subjectSulfoneen
dc.subjectNickelen
dc.titleTRANSITION METAL CATALYZED CROSS-COUPLINGS OF ALKYL SULFONE ELECTROPHILESen
dc.typethesisen
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