Stereoselective reactions of N-acyl thiazolidinethiones with trimethyl orthoformate, acetals and diarylmethyl ethers catalyzed by nickel(II) complexes

In this Doctoral Thesis a new stereoselective Ni(II)–mediated catalytic system for the SN1–like addition of chiral N­acyl thiazolidinethiones to electrophiles able to deliver cationic species under acidic conditions has been developed. Importantly, the nickel(II) complexes used along our studies are...

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Autor: Romo Fernández, Juan Manuel
Formato: tesis doctoral
Estado:Versión publicada
Fecha de publicación:2015
País:España
Recursos:CBUC, CESCA
Repositorio:TDR. Tesis Doctorales en Red
OAI Identifier:oai:www.tdx.cat:10803/301278
Acesso em linha:http://hdl.handle.net/10803/301278
Access Level:acceso abierto
Palavra-chave:Catàlisi
Catálisis
Catalysis
Níquel
Nickel
Ciències Experimentals i Matemàtiques
547
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network_acronym_str ES
network_name_str España
repository_id_str
dc.title.none.fl_str_mv Stereoselective reactions of N-acyl thiazolidinethiones with trimethyl orthoformate, acetals and diarylmethyl ethers catalyzed by nickel(II) complexes
title Stereoselective reactions of N-acyl thiazolidinethiones with trimethyl orthoformate, acetals and diarylmethyl ethers catalyzed by nickel(II) complexes
spellingShingle Stereoselective reactions of N-acyl thiazolidinethiones with trimethyl orthoformate, acetals and diarylmethyl ethers catalyzed by nickel(II) complexes
Romo Fernández, Juan Manuel
Catàlisi
Catálisis
Catalysis
Níquel
Nickel
Ciències Experimentals i Matemàtiques
547
title_short Stereoselective reactions of N-acyl thiazolidinethiones with trimethyl orthoformate, acetals and diarylmethyl ethers catalyzed by nickel(II) complexes
title_full Stereoselective reactions of N-acyl thiazolidinethiones with trimethyl orthoformate, acetals and diarylmethyl ethers catalyzed by nickel(II) complexes
title_fullStr Stereoselective reactions of N-acyl thiazolidinethiones with trimethyl orthoformate, acetals and diarylmethyl ethers catalyzed by nickel(II) complexes
title_full_unstemmed Stereoselective reactions of N-acyl thiazolidinethiones with trimethyl orthoformate, acetals and diarylmethyl ethers catalyzed by nickel(II) complexes
title_sort Stereoselective reactions of N-acyl thiazolidinethiones with trimethyl orthoformate, acetals and diarylmethyl ethers catalyzed by nickel(II) complexes
dc.creator.none.fl_str_mv Romo Fernández, Juan Manuel
author Romo Fernández, Juan Manuel
author_facet Romo Fernández, Juan Manuel
author_role author
dc.contributor.none.fl_str_mv Urpí Tubella, Fèlix
Romea, Pedro
Urpí Tubella, Fèlix
Universitat de Barcelona. Departament de Química Orgànica
dc.subject.none.fl_str_mv Catàlisi
Catálisis
Catalysis
Níquel
Nickel
Ciències Experimentals i Matemàtiques
547
topic Catàlisi
Catálisis
Catalysis
Níquel
Nickel
Ciències Experimentals i Matemàtiques
547
description In this Doctoral Thesis a new stereoselective Ni(II)–mediated catalytic system for the SN1–like addition of chiral N­acyl thiazolidinethiones to electrophiles able to deliver cationic species under acidic conditions has been developed. Importantly, the nickel(II) complexes used along our studies are structurally simple, commercially available and easy to handle. These complexes coordinate to thioimides to generate an intermediate that, after deprotonation, afford a putative nickel(II) enolate, which is the real nucleophile. In Chapter 1, a totally stereoselective addition of N­acyl thiazolidinethiones to trimethyl orthoformate activated by TESOTf has been optimized. The use of this Lewis acid is also crucial for the activation of the catalyst. For N­arylacetyl thiazolidinethiones, reactions with 2.5 mol% of (Ph3P)2NiCl2 and a temperature between –20 ºC and 0 ºC was required. Instead, when other N­acyl groups were used, up to 20 mol% of (Ph3P)2NiCl2 was necessary. Alternatively, a 2.5–5 mol% of (Me3P)2NiCl2 can be used, as long as the reaction temperature is –20 ºC to avoid the appearance of byproducts. The resultant adducts are obtained between 71–94% yield and they can be converted easily in enantiomerically pure compounds with a wide array of different functional groups. This method has been applied successfully to the stereoselective synthesis of the side chain of (–)­pyridovericin and the C11–C19 fragment of (+)­peloruside A, with overall yields of 44% and 4%, respectively. In Chapter 2, the Ni(II)­mediated catalytic system was next applied to commercially available cationic salts such as 1,3­benzodithiolylium tetrafluoroborate, the Eschemoser’s salt and the tropylium tetrafluoroborate. Although the results were not highly satisfactory, the obtention of the corresponding adducts support a SN1 mechanism. Furthermore, a new stereoselective Ni(II) catalyzed alkylation reaction with diarylcarbenium methyl ethers has been developed. The reaction proceeds smoothly provided that the carbocationic intermediate is stable enough. The Mayr’s scale of electrophilicity accounts for this evidence. In Chapter 3, the catalytic system has been applied to acetals, which involved the challenging construction of two new stereocenters in a single reaction. The reaction provides the corresponding anti adducts with aromatic, a,ß­unsaturated and Co–propargylic acetals in low to moderate yields. The stereoselectivity of these additions strongly depends on the structure of the acetal. Particularly, acetals that furnish stable oxonium cations give the best stereocontrol, up to 83:17 diastereomeric ratio. Finally, Chapter 4 refers to our studies on the use of chiral N­glycolyl thiazolidinethiones in the Ni(II) catalyzed reaction to prepare anti­a,ß­dihydroxycarboxyl compounds from aromatic, a,ß­unsaturated cobalt–derived propargylic acetals in moderate to high yields. Therefore, this method provides a new method towards enantiomerically pure 1,2,3­trioxygenated systems. The diastereomeric ratios observed in these reactions resulted to be from good (75:25) to excellent (94:6). A thorough analysis of the reaction conditions uncovered that acetals difficult to be activated require an excess of Lewis acid or acetal. All together, these results proved that the Lewis acid–mediated addition of chiral N­acyl thiazolidinethiones to a wide range of electrophiles catalyzed by structurally simple, commercially available and easy to handle nickel(II) complexes is a very efficient method for the stereoselective construction of carbon–carbon bonds. Likely, such a transformation proceeds through a SN1–like mechanism in which a putative nickel(II) enolate adds to a cationic intermediate generated in situ from orthoesters, acetals or ethers. The chiral auxiliary can be removed easily to afford an important number of enantiomerically pure compounds. The synthetic potential of this new method has been demonstrated in the preparation of the side chain of pyridovericin and the C11–C19 fragment of peloruside A.
publishDate 2015
dc.date.none.fl_str_mv 2015
2015
2015
dc.type.none.fl_str_mv info:eu-repo/semantics/doctoralThesis
info:eu-repo/semantics/publishedVersion
format doctoralThesis
status_str publishedVersion
dc.identifier.none.fl_str_mv http://hdl.handle.net/10803/301278
url http://hdl.handle.net/10803/301278
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv 390 p.
application/pdf
application/pdf
dc.publisher.none.fl_str_mv Universitat de Barcelona
publisher.none.fl_str_mv Universitat de Barcelona
dc.source.none.fl_str_mv TDX (Tesis Doctorals en Xarxa)
reponame:TDR. Tesis Doctorales en Red
instname:CBUC, CESCA
instname_str CBUC, CESCA
reponame_str TDR. Tesis Doctorales en Red
collection TDR. Tesis Doctorales en Red
repository.name.fl_str_mv
repository.mail.fl_str_mv
_version_ 1869410059200495616
spelling Stereoselective reactions of N-acyl thiazolidinethiones with trimethyl orthoformate, acetals and diarylmethyl ethers catalyzed by nickel(II) complexesRomo Fernández, Juan ManuelCatàlisiCatálisisCatalysisNíquelNickelCiències Experimentals i Matemàtiques547In this Doctoral Thesis a new stereoselective Ni(II)–mediated catalytic system for the SN1–like addition of chiral N­acyl thiazolidinethiones to electrophiles able to deliver cationic species under acidic conditions has been developed. Importantly, the nickel(II) complexes used along our studies are structurally simple, commercially available and easy to handle. These complexes coordinate to thioimides to generate an intermediate that, after deprotonation, afford a putative nickel(II) enolate, which is the real nucleophile. In Chapter 1, a totally stereoselective addition of N­acyl thiazolidinethiones to trimethyl orthoformate activated by TESOTf has been optimized. The use of this Lewis acid is also crucial for the activation of the catalyst. For N­arylacetyl thiazolidinethiones, reactions with 2.5 mol% of (Ph3P)2NiCl2 and a temperature between –20 ºC and 0 ºC was required. Instead, when other N­acyl groups were used, up to 20 mol% of (Ph3P)2NiCl2 was necessary. Alternatively, a 2.5–5 mol% of (Me3P)2NiCl2 can be used, as long as the reaction temperature is –20 ºC to avoid the appearance of byproducts. The resultant adducts are obtained between 71–94% yield and they can be converted easily in enantiomerically pure compounds with a wide array of different functional groups. This method has been applied successfully to the stereoselective synthesis of the side chain of (–)­pyridovericin and the C11–C19 fragment of (+)­peloruside A, with overall yields of 44% and 4%, respectively. In Chapter 2, the Ni(II)­mediated catalytic system was next applied to commercially available cationic salts such as 1,3­benzodithiolylium tetrafluoroborate, the Eschemoser’s salt and the tropylium tetrafluoroborate. Although the results were not highly satisfactory, the obtention of the corresponding adducts support a SN1 mechanism. Furthermore, a new stereoselective Ni(II) catalyzed alkylation reaction with diarylcarbenium methyl ethers has been developed. The reaction proceeds smoothly provided that the carbocationic intermediate is stable enough. The Mayr’s scale of electrophilicity accounts for this evidence. In Chapter 3, the catalytic system has been applied to acetals, which involved the challenging construction of two new stereocenters in a single reaction. The reaction provides the corresponding anti adducts with aromatic, a,ß­unsaturated and Co–propargylic acetals in low to moderate yields. The stereoselectivity of these additions strongly depends on the structure of the acetal. Particularly, acetals that furnish stable oxonium cations give the best stereocontrol, up to 83:17 diastereomeric ratio. Finally, Chapter 4 refers to our studies on the use of chiral N­glycolyl thiazolidinethiones in the Ni(II) catalyzed reaction to prepare anti­a,ß­dihydroxycarboxyl compounds from aromatic, a,ß­unsaturated cobalt–derived propargylic acetals in moderate to high yields. Therefore, this method provides a new method towards enantiomerically pure 1,2,3­trioxygenated systems. The diastereomeric ratios observed in these reactions resulted to be from good (75:25) to excellent (94:6). A thorough analysis of the reaction conditions uncovered that acetals difficult to be activated require an excess of Lewis acid or acetal. All together, these results proved that the Lewis acid–mediated addition of chiral N­acyl thiazolidinethiones to a wide range of electrophiles catalyzed by structurally simple, commercially available and easy to handle nickel(II) complexes is a very efficient method for the stereoselective construction of carbon–carbon bonds. Likely, such a transformation proceeds through a SN1–like mechanism in which a putative nickel(II) enolate adds to a cationic intermediate generated in situ from orthoesters, acetals or ethers. The chiral auxiliary can be removed easily to afford an important number of enantiomerically pure compounds. The synthetic potential of this new method has been demonstrated in the preparation of the side chain of pyridovericin and the C11–C19 fragment of peloruside A.En la presente tesis doctoral se ha desarrollado un nuevo sistema catalítico estereoselectivo basado en complejos de níquel(II) para la adición tipo SN1 de N­acil tiazolidintionas quirales a electrófilos capaces de generar especies carbocatiónicas en condiciones ácidas. Los complejos de níquel(II) usados a lo largo de los respectivos estudios son estructuralmente simples, comercialmente disponibles y baratos, y fáciles de manipular y almacenar. En el Capítulo 1 se ha optimizado y desarrollado una adición totalmente estereoselectiva catalizada por complejos de tipo (R3P)2NiCl2 de N­acil tiazolidintionas a ortoformiato de trimetilo activado por un ácido de Lewis, lo que permite la introducción de un grupo formilo en la posición ß. Esta reacción pasa por la generación catalítica de un presunto enolato de níquel(II). Mientras que la reacción con N­arilacetil tioimidas funcionan satisfactoriamente con un 2.5 mol% de (Ph3P)2NiCl2, otro tipo de N­acil tioimidas requieren de una carga del 5 mol% de (Me3P)2NiCl2. Esta reacción ha sido aplicada en la preparación de la cadena lateral de la (–)­piridovericina y el fragmento C11–C19 de la pelorusida A. En el Capítulo 2, este sistema catalítico fue aplicado a diferentes sales carbocatiónicas comercialmente disponibles con resultados moderados. No obstante, la obtención de los aductos de adición demuestra la viabilidad del sistema hacia otros electrófilos mediante una reacción del tipo SN1. Aprovechando la potencialidad de este sistema catalítico, se ha desarrollado una nueva reacción de alquilación estereoselectiva con diarilmetil metil éteres. La reacción funciona increíblemente bien siempre y cuando los intermedios carbocatiónicos sean lo suficientemente estables. En el Capítulo 3 se desarrolla la adición de enolatos de níquel(II) de N­propanoíltiazolidintionas generadas en cantidades catalíticas a acetales, que fue extrapolada posteriormente a N­hidroxiacetil tioimidas debidamente protegidas en el Capítulo 4. Estas reacciones proporcionan aductos con dos nuevos centros estereogénicos con estereoquímica relativa anti. El método es aplicable a acetales aromáticos, a,ß–insaturados y propargílicos cobaltados y, en el caso de la N­propanoíltiazolidintiona, se obtienen rendimientos de moderados a buenos y relaciones diastereoméricas modestas (60:40–83:17) Estos resultados son notablemente mejores por lo que hace al uso de N­hidroxiacetil tioimidas (Capítulo 4), que muestran diastereoselectividades que llegan al valor de 94:6.Universitat de BarcelonaUrpí Tubella, FèlixRomea, PedroUrpí Tubella, FèlixUniversitat de Barcelona. Departament de Química Orgànica201520152015info:eu-repo/semantics/doctoralThesisinfo:eu-repo/semantics/publishedVersion390 p.application/pdfapplication/pdfhttp://hdl.handle.net/10803/301278TDX (Tesis Doctorals en Xarxa)reponame:TDR. Tesis Doctorales en Redinstname:CBUC, CESCAInglésADVERTIMENT. L'accés als continguts d'aquesta tesi doctoral i la seva utilització ha de respectar els drets de la persona autora. Pot ser utilitzada per a consulta o estudi personal, així com en activitats o materials d'investigació i docència en els termes establerts a l'art. 32 del Text Refós de la Llei de Propietat Intel·lectual (RDL 1/1996). Per altres utilitzacions es requereix l'autorització prèvia i expressa de la persona autora. En qualsevol cas, en la utilització dels seus continguts caldrà indicar de forma clara el nom i cognoms de la persona autora i el títol de la tesi doctoral. No s'autoritza la seva reproducció o altres formes d'explotació efectuades amb finalitats de lucre ni la seva comunicació pública des d'un lloc aliè al servei TDX. Tampoc s'autoritza la presentació del seu contingut en una finestra o marc aliè a TDX (framing). Aquesta reserva de drets afecta tant als continguts de la tesi com als seus resums i índexs.info:eu-repo/semantics/openAccessoai:www.tdx.cat:10803/3012782026-06-14T12:46:07Z
score 15,301603

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