Catalytic stereoselective [2,3]-rearrangement reactions

The authors thank the Royal Society for a University Research Fellowship (A.D.S.), the European Research Council under the European Union’s Seventh Framework Programme (FP7/2007-20013) ERC Grant Agreement No. 279850 (J.E.T., T.H.W., K.K.), and the European Union (Marie Curie ITN ‘SuBiCat’ PITN-GA-2013-607044) (S.S.M.S.) for financial support.[2,3]-Sigmatropic rearrangement processes of allylic ylides or their equivalents can be applied to a variety of different substrates and generate products of wide interest and applicability to organic synthesis. This review describes the development and applications of stereoselective [2,3]-rearrangement reactions in which a sub-stoichiometric amount of a catalyst is used in either the formation of the reactive intermediate or the [2,3]-rearrangement step itself.PostprintPeer reviewe

Tandem palladium and isothiourea relay catalysis : enantioselective synthesis of α-amino acid derivatives via allylic amination and [2,3]-sigmatropic rearrangement

The research leading to these results (S.S.M.S.) has received funding from the European Union (Marie Curie ITN “SubiCat” PITN-GA-2013-607044) and the ERC under the European Union's Seventh Framework Programme (FP7/2007-2013)/E.R.C. grant agreement no 279850 (T.H.W., J.E.T.). A.D.S. thanks the Royal Society for a Wolfson Research Merit Award.A tandem relay catalytic protocol using both Pd and isothiourea catalysis has been developed for the enantioselective synthesis of α-amino acid derivatives containing two stereogenic centers from readily accessible N,N-disubstituted glycine aryl esters and allylic phosphates. The optimized process uses a bench-stable succinimide-based Pd precatalyst (FurCat) to promote Pd-catalyzed allylic ammonium salt generation from the allylic phosphate and the glycine aryl ester. Subsequent in situ enantioselective [2,3]-sigmatropic rearrangement catalyzed by the isothiourea benzotetramisole forms syn-α-amino acid derivatives with high diastereo- and enantioselectivity. This methodology is most effective using 4-nitrophenylglycine esters and tolerates a variety of substituted cinnamic and styrenyl allylic ethyl phosphates. The use of challenging unsymmetrical N-allyl-N-methylglycine esters is also tolerated under the catalytic relay conditions without compromising stereoselectivity.Publisher PDFPeer reviewe

Isothiourea-catalysed chemo- and enantioselective [2,3]-sigmatropic rearrangements of N,N-diallyl allylic ammonium ylides

The research leading to these results (T.H.W.) has received funding from the ERC under the European Union's Seventh Framework Programme (FP7/2007–2013)/E.R.C. grant agreement n° 279850 and the European Union (Marie Curie ITN “SubiCat” PITN-GA-2013-607044) (S. S. M. S.). A.D.S. thanks the Royal Society for a Wolfson Research Merit Award. The data underpinning this publication can be found at DOI: http://dx.doi.org/10.17630/f522b48d-ed02–42b3-a161-54687ea5af57The isothiourea-catalysed chemo- and enantioselective [2,3]-sigmatropic rearrangement of N,N-diallyl allylic ammonium ylides is explored as a key part of a route to free functionalised α-amino esters and piperidines. The [2,3]-sigmatropic rearrangement proceeds with excellent diastereo- and enantiocontrol (>95:5 dr, up to 97% ee), with the resultant N,N-diallyl α-amino esters undergoing either mono- or bis-N-allyl deprotection. Bis-N-allyl deprotection leads to free α-amino esters, while the mono-deprotection strategy has been utilized in the synthesis of a target functionalised piperidine.PostprintPeer reviewe

Les explorations visuelles d'expressions faciales émotionnelles chez les bébés de 6 mois et chez les adultes

Les études concernant les compétences du jeune bébé sont nombreuses et ont montré à plusieurs reprises son intérêt précoce pour les stimuli humains. Dans notre étude, nous nous sommes intéressés aux visages et aux informations dont ils sont porteurs. Plus précisément, nous avons analysé les explorations visuelles de nos participants, face à des visages présentant des émotions. Sur quelles caractéristiques internes du visage portent-ils leur attention et cette dernière varie-telle selon l’âge ? Afin de tenter d’y répondre, nous avons testé la préférence visuelle des adultes, âgés de 24 ans en moyenne et des bébés de 6 mois, à l’aide d’un eye-tracker. Comme prédit, les yeux sont la zone la plus regardée du visage. Conformément à l’une de nos hypothèses, la bouche est davantage regardée par les adultes lors de l’émotion de joie, mais nous trouvons l’inverse chez les bébés

Tandem allylic amination and [2,3]-rearrangement for the synthesis of enantioenriched α-amino acid derivatives

This thesis details the development of tandem allylic amination and [2,3]-rearrangement methodologies for the synthesis of enantioenriched α-amino ester derivatives. Chapter 1 aims to introduce [2,3]-sigmatropic rearrangements and give an overview of the relevant literature precedents in terms of catalytic stereoselective [2,3]-rearrangements of allylic ammonium ylides. The different types of tandem catalytic processes and some key examples are then discussed. Finally, the aims of this thesis are presented. Chapter 2 details the development of a tandem palladium and isothiourea relay catalysis for the enantioselective [2,3]-rearrangement of allylic ammonium ylides. In this one-pot methodology, the intermediate ammonium salt is generated in situ via a palladium catalysed allylic amination. The subsequent enantioselective [2,3]-rearrangement is promoted by a chiral isothiourea catalyst to generate syn-α-amino ester derivatives in moderate to high yield (32-91%) and excellent stereocontrol (up to >95:5 dr and >99:1 er). The synthetic utility of the products is then demonstrated with a range of derivatisation reactions. Moreover, mechanistic experiments give insight into the mechanism of this palladium/isothiourea relay catalysis. Chapter 3 focuses on the synthesis of enantioenriched pyrrolidines via a tandem palladium-catalysed allylic amination/[2,3]-rearrangement methodology. Starting from enantiopure proline-derivatives, pyrrolidines were obtained in good to excellent yield (61-94%) and diastereoselectivity (up to 91:9 dr) with moderate enantioenrichment (up to 80:20 er). This process relies on transfer of chirality from the starting material to the product. Chapter 4 summarises the work described in this thesis and discusses potential future work within the area

Enantioselective α-Allylation of Acyclic Esters using B(pin)-Substituted Electrophiles: Independent Regulation of Stereocontrol Elements via Cooperative Pd/Lewis Base Catalysis

Cooperation between a Lewis base and Pd catalyst enables the direct enantioselective α-functionalization of aryl and vinyl acetic acid esters using a bifunctional B(pin)-substituted electrophile. Critical to the success of this method was the recognition that both catalysts could control the necessary stereochemical aspects; the Lewis base catalyst controls the enantioselectivity of the reaction, whereas the Pd catalyst regulates alkenyl-B(pin) configuration. This is the first example of using cooperative catalysis to control both stereochemical features during Pd-catalyzed allylic alkylation