Regiodivergent Lewis base-promoted O- to C-carboxyl transfer of furanyl carbonates

The authors would like to thank the Royal Society for a University Research Fellowship (ADS), The Carnegie Trust for the Universities of Scotland (CDC and LCM) and the EPSRC (CJ) for funding, and the EPSRC National Mass Spectrometry Service Centre (Swansea).Triazolinylidenes promote γ-selective C-carboxylation (up to 99 : 1 regioselectivity) in the O- to C-carboxyl transfer of furanyl carbonates in contrast to DMAP that promotes preferential α-C-carboxylation with moderate regiocontrol (typically 60 : 40 regioselectivity). The generality of this process is described and a simple mechanistic and kinetic model postulated to account for the observed regioselectivityPublisher PDFPeer reviewe

Isothiourea-promoted O- to C-carboxyl transfer reactions

This thesis describes an extensive investigation of the O- to C-carboxyl transfer of oxazolyl carbonates using isothioureas as Lewis base catalysts. The structural requirements of simple bicyclic amidines and isothioureas to promote this transformation have been investigated, showing that the catalytic efficiency and product distribution of these reactions are markedly affected by the catalyst structure. The optimal isothiourea catalyst was efficiently applied to the rearrangement of a wide range of oxazolyl, benzofuranyl and indolyl carbonates. The structural motif of tetrahydropyrimidine-based isothioureas has then been evaluated in order to develop an asymmetric variant of the O- to C-carboxyl transfer of oxazolyl carbonates. A number of chiral isothioureas bearing stereodirecting groups in C(2) and/or C(3) have been synthesised and used in this rearrangement, showing that a C(2)-stereodirecting unit is essential for high enantioselectivity, with an additional C(3)-substituent increasing the reactivity. The optimal chiral C(2)-substituted isothioureas identified are general and efficient asymmetric catalysts for O- to C-carboxyl transfer of oxazolyl carbonates, generating a quaternary stereocentre with high enantioselectivity (up to 94% ee). The origin of the enantioselectivity of this process has been probed mechanistically and rationalised computationally. Having gained an insight into the structural motifs of isothioureas required to impart good catalytic activity and asymmetric induction in the O- to C-carboxyl transfer of oxazolyl carbonates, the mechanism of this reaction was probed using kinetic and mechanistic experiments. ¹⁹F NMR spectroscopic analysis allowed the evolution of product, by-product and intermediate throughout the reaction to be monitored while a number of crossover and stability experiments gave additional information about the catalytic cycle. Extension to a related system has been demonstrated with the O- to C-carboxyl transfer of furanyl carbonates, producing a mixture of α- and γ-butenolides depending on the nature of the Lewis base employed. DMAP gives a mixture of both regioisomers with a preference for the α-regioisomer, while NHCs lead predominantly to the γ-regioisomer. Chiral isothioureas have been used to promote this rearrangement, giving the major α-regioisomer with good enantioselectivity (up to 83% ee). To quantify the different reactivities observed with these isothioureas, their nucleophilicities and Lewis basicities using the stopped-flow technique have been determined. Finally, model studies toward the synthesis of the natural product calcaridine A, using the methodology developed herein, have been investigated

Nucleophilicities and Lewis Basicities of Isothiourea Derivatives

Rate and equilibrium constants for the reactions of a series of isothioureas with benzhydrylium ions have been measured photometrically. The data were employed to determine the nucleophilicities and nucleofugalities of isothioureas and compare them with those of other organocatalysts.</p

Isothiourea-mediated one-pot synthesis of functionalized pyridines

This work was supported by the Royal Society, Syngenta/EPSRC, The Carnegie Trust for the Universities of Scotland and ERC.Publisher PDFPeer reviewe

Isothiourea-Catalyzed Asymmetric O- to C-Carboxyl Transfer of Furanyl Carbonates

The Lagos-Wright model -- a monetary model in which pairwise meetings alternate in time with a centralized meeting -- has been extensively analyzed, but always using particular trading protocols. Here, trading protocols are replaced by two alternative notions of implementability: one that allows only individual defections and one that also allows cooperative defections in meetings. It is shown that the rst-best allocation is implementable under the stricter notion without taxation if people are su ciently patient. And, if people are free to skip the centralized meeting, then lump-sum taxation used to pay interest on money does not enlarge the set of implementable allocations