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Fe-Catalyzed Cross-Coupling of 1-Substituted Cyclopropyl Tosylates & Rh(III) Complexes in Carbene Transfer Reactions: Development of an Azo Metathesis

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Fe-Catalyzed Cross-Coupling of 1-Substituted Cyclopropyl Tosylates & Rh(III) Complexes in Carbene Transfer Reactions: Development of an Azo Metathesis Fe-Catalyzed Cross-Coupling of 1-Substituted Cyclopropyl Tosylates & Rh(III) Complexes in Carbene Transfer Reactions: Development of an Azo Metathesis Dissertation zur Erlangung des akademischen Grades eines Doktors der Naturwissenschaften (Dr. rer. nat.) des Fachbereichs Chemie und chemische Biologie der Technischen Universität Dortmund vorgelegt von Daniel James Tindall geboren am 26.11.1989 in Peine Mülheim a. d. Ruhr, 2018 Eidesstattliche Versicherung (Affidavit) Tindall, Daniel James_________ 182981_______________________ Name, Vorname Matrikel-Nr. (Surname, first name) (Enrolment number) Belehrung: Official notification: Wer vorsätzlich gegen eine die Täuschung über Prü- fungsleistungen betreffende Regelung einer Hochschul- Any person who intentionally breaches any regulation of prüfungsordnung verstößt, handelt ordnungswidrig. Die university examination regulations relating to deception in examination performance is acting improperly. This Ordnungswidrigkeit kann mit einer Geldbuße von bis zu 50.000,00 € geahndet werden. Zuständige Verwaltungs- offence can be punished with a fine of up to EUR behörde für die Verfolgung und Ahndung von Ordnungs- 50,000.00. The competent administrative authority for widrigkeiten ist der Kanzler/die Kanzlerin der Techni- the pursuit and prosecution of offences of this type is the schen Universität Dortmund. Im Falle eines mehrfachen chancellor of the TU Dortmund University. In the case of oder sonstigen schwerwiegenden Täuschungsversu- multiple or other serious attempts at deception, the ches kann der Prüfling zudem exmatrikuliert werden, § candidate can also be unenrolled, Section 63, 63 Abs. 5 Hochschulgesetz NRW. paragraph 5 of the Universities Act of North Rhine- Westphalia. Die Abgabe einer falschen Versicherung an Eides statt ist strafbar. The submission of a false affidavit is punishable. Wer vorsätzlich eine falsche Versicherung an Eides statt Any person who intentionally submits a false affidavit abgibt, kann mit einer Freiheitsstrafe bis zu drei Jahren can be punished with a prison sentence of up to three oder mit Geldstrafe bestraft werden, § 156 StGB. Die years or a fine, Section 156 of the Criminal Code. The fahrlässige Abgabe einer falschen Versicherung an negligent submission of a false affidavit can be punished Eides statt kann mit einer Freiheitsstrafe bis zu einem with a prison sentence of up to one year or a fine, Jahr oder Geldstrafe bestraft werden, § 161 StGB. Section 161 of the Criminal Code. I have taken note of the above official notification. Die oben stehende Belehrung habe ich zur Kenntnis genommen: Mülheim a. d. Ruhr, 11.04.2018_ _________________________ Ort, Datum Unterschrift (Place, date) (Signature) Titel der Dissertation: (Title of the thesis): Fe-Catalyzed Cross-Coupling of 1-Substituted Cyclopropyl Tosylates &_________________ Rh(III) Complexes in Carbene Transfer Reactions: Development of an Azo Metathesis_____ _________________________________________________________________________________ Ich versichere hiermit an Eides statt, dass ich die vorlie- I hereby swear that I have completed the present gende Dissertation mit dem Titel selbstständig und ohne dissertation independently and without inadmissible unzulässige fremde Hilfe angefertigt habe. Ich habe external support. I have not used any sources or tools keine anderen als die angegebenen Quellen und Hilfs- other than those indicated and have identified literal and mittel benutzt sowie wörtliche und sinngemäße Zitate analogous quotations. kenntlich gemacht. The thesis in its current version or another version has Die Arbeit hat in gegenwärtiger oder in einer anderen not been presented to the TU Dortmund University or Fassung weder der TU Dortmund noch einer anderen another university in connection with a state or Hochschule im Zusammenhang mit einer staatlichen academic examination.* oder akademischen Prüfung vorgelegen. *Please be aware that solely the German version of the affidavit ("Eidesstattliche Versicherung") for the PhD thesis is the official and legally binding version. Mülheim a. d. Ruhr, 11.04.2018_ _______________________ Ort, Datum Unterschrift (Place, date) (Signature) Die vorliegende Arbeit entstand unter Anleitung von Prof. Dr. Alois Fürstner in der Zeit von Februar 2015 bis März 2018 am Max-Planck-Institut für Kohlenforschung in Mülheim an der Ruhr. Teile dieser Arbeit wurden bereits in folgenden Beiträgen veröffentlicht: „Iron-Catalyzed Cross-Coupling of 1-Alkynylcyclopropyl Tosylates and Related Substrates” D. J. Tindall, H. Krause, A. Fürstner Adv. Synth. Catal. 2016, 358, 2398–2403. „Structure and Reactivity of Half-Sandwich Rh(+3) and Ir(+3) Carbene Complexes. Catalytic Metathesis of Azobenzene Derivatives“ D. J. Tindall, C. Werlé, R. Goddard, P. Philipps, C. Farès, A. Fürstner J. Am. Chem. Soc.. 2018, 140, 1884–1893. Die praktischen Arbeiten erfolgten zum Teil in Zusammenarbeit mit Helga Krause (Kapitel 2.2.1) und Dr. Christophe Werlé (Kapitel 3.2.1). Die beschriebenen Ergebnisse bilden eine vollständige Darstellung dieser gemeinsamen Arbeiten. Die von diesen Mitarbeitern alleinverantwortlich erzielten Ergebnisse wurden als solche an entsprechender Stelle gekennzeichnet. 1. Berichterstatter: Herr Prof. Dr. Alois Fürstner 2. Berichterstatter: Herr Prof. Dr. Norbert Krause Meinen Eltern Life is too long to be taken seriously all the time. A little bit of humour helps! I Abstract A novel Fe-catalyzed cross-coupling of 1-alkynylcyclopropyl tosylates 37 and alkyl Grignard reagents was developed, which represents the first Fe-catalyzed cross-coupling of tert-alkyl electrophiles. The protocol allows regioselective access to the direct (SN2-type) substitution products 38 (Scheme 1, top), in contrast to related Fe-catalyzed processes involving propargylic substrates which furnish exclusively the SN2’-type allene products. In addition, 1-vinyl- cyclopropyl tosylates 170 afforded the desired cross-coupling products 171 when reacted with MeMgCl. If β-hydrogens were available on the nucleophile, mixtures of the cross-coupling product 172 along with the reduced and the dimerized starting material (45 and 46, respectively) were obtained (Scheme 1, bottom). 1-Aryl- and 1-alkylcyclopropyl tosylates do not undergo this transformation which suggests that coordination of the substrate to the iron catalyst is necessary to allow for successful cross-coupling. Based on this observation, the more efficient reaction of 37 compared to that of 170 is explained by the higher binding affinity of the alkyne to the iron catalyst, thereby suppressing side reactions. Scheme 1: Fe-catalyzed cross-coupling of 1-alkynyl- and 1-vinylcyclopropyl tosylates with alkylmagnesium halides. Secondly, studies on Rh(III) complexes in carbene transfer reactions showed that carbene formation and migratory insertion are likely to be fast steps in Rh(III)-mediated C–H functionalization of arenes (Scheme 2, left). The presence of a labile ligand and the absence of inorganic impurities were essential for the conversion of 99 into 101. Additionally, piano-stool complexes of the type [Cp*MX2]2 (M = Rh, Ir; X = Cl, Br, I) were shown to catalyze a representative set of carbene transfer reactions. Only [Cp*RhCl2]2 was found to be a poor catalyst, which is explained by the formation of C-metalated rhodium enolate 89 rather than the expected carbene complex 94 (Scheme 2, right). I Scheme 2: a) Synthesis of a cyclometalated Rh(III) complex (101) though migratory insertion of a carbene derived from bis(4-methoxyphenyl)diazomethane (100, red). b) Rh(III) carbenoid complex 89 and Rh(III) carbene complex 94. Thirdly, a Rh(III)-catalyzed metathesis of diazo compounds 173 and azoarenes 174 affording α- imino esters 175 was developed (Scheme 3, top). Key to the success and scalability of the reaction was irradiation of the reaction mixture with blue LEDs which facilitate the E→Z isomerization of the azoarene and sets the scene for the metathesis to occur. This trans- formation represents a new type of reaction of donor/acceptor carbenes and shows a broad scope with high yields and an appreciable compatibility with polar and apolar substituents giving rise to α-imino esters which could not easily be synthesized by traditional means. Mechanistic investigations argue against the intermediacy of a metal nitrene formed via the archetypal [2+2]/retro-[2+2] cycloaddition mechanism. Instead, reaction of rhodium carbene complex 95 and (Z)-azobenzene (117) forms a transient diaziridine 157 which was characterized by X-ray crystallography (Scheme 3, bottom). This intermediate can form the α- imino esters through two possible pathways: either a metal-free (bimolecular) decay of the three-membered ring releases the product 175 alongside (E)-azobenzene, which then re-enters the catalytic cycle, or the diaziridine 157 reacts with another rhodium carbene complex 95 leading to the product and regeneration of the catalyst, presumably via a cheletropic process. Scheme 3: Rh(III)-catalyzed metathesis of diazo compounds 173 and azoarenes 174. II II Übersicht Es wurde eine neuartige Fe-katalysierte Kreuzkupplung entwickelt, die zum ersten Mal tertiäre Elektrophile (1-Alkinylcyclopropyltosylate 37) mit Alkyl-Grignard-Verbindungen kreuzkuppelt (Schema 1, oben). Sie erlaubt den regioselektiven Zugang zu den SN2-artigen Substitutions- produkten 38, während vergleichbare Fe-katalysierten Kreuzkupplungen mit propargylischen Substraten ausschließlich Allene (SN2‘-Produkte) liefern. Weiterhin wurden aus 1-Vinylcyclo- propyltosylaten 170 mit MeMgCl die Kreuzkupplungsprodukte
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