Enantioselective synthesis of β-fluoro-β-aryl-α-amino pentenamides by organocatalytic [2,3]-sigmatropic rearrangement

The research leading to these results (K.K.) has received funding from the ERC under the European Union's Seventh Framework Programme (FP7/2007-2013) / ERC grant agreement n° 279850. A.D.S. thanks the Royal Society for a Wolfson Research Merit Award.The tetramisole-promoted catalytic enantioselective [2,3]-sigmatropic rearrangement of quaternary ammonium salts bearing a (Z)-3-fluoro-3-arylprop-2-ene group generates, after addition of benzylamine, a range of β-fluoro-β-aryl-α-aminopentenamides containing a stereogenic tertiary fluorine substituent. Cyclic and acyclic nitrogen substituents as well as various aromatic substituents are tolerated, giving the β-fluoro-β-aryl-α-aminopentenamide products in up to 76% yield, 96:4 dr, and 98:2 er.PostprintPeer reviewe

Effect of ligand backbone on the selectivity and stability of rhodium hydroformylation catalysts derived from phospholane-phosphites

We thank the Eastman Chemical Company for funding and permission to publish. M.B. thanks the School of Chemistry and EaStCHEM for support.A study on how ligand backbone structure has an impact on selectivity, rate, and catalyst stability of hydroformylation catalysts was prompted by some longer-term stability issues being discovered for a phospholane-phosphite with a [−CH2O−] backbone. A series of phospholane-phosphite ligands were synthesized. Catalysts made in situ from these ligands and [Rh(acac)(CO)2] were found to give iso-butanal selectivities up to 75% at temperatures between 75 and 105 °C: the latter being a benchmark for iso-selectivity in reactions conducted at industrially meaningful temperatures. A racemic rhodium complex of a bidentate phospholane-phosphite from a tropos-biphenol with an extended backbone showed unusually high stability at high temperatures, combined with even better iso-selectivity in propene hydroformylation relative to the original complex. A related ligand with an electron-withdrawing group maintained the unusually high stability and improved activity. Characterization of the precatalysts of type [RhH(CO)2(L)] was accomplished using in situ HPIR spectroscopy and backed up by density functional theory calculations (B3PW91-D3 level) and by NMR studies; the latter showed that the variation of the backbone also had a pronounced impact on the precatalyst structure. A key finding is that it is now possible to prepare phospholane-phosphite ligands that deliver high iso-butanal selectivity and that show no signs of degradation after several days even above typical reaction temperatures. In one stability test, several kilograms of aldehydes were produced with TOF and selectivity being consistent over several days.PostprintPeer reviewe

Unveiling the impact of a CF2 motif in the isothiourea catalyst skeleton : evaluating C(3)-F2-HBTM and its catalytic activity

The St Andrews Team (A. D. S., K. K., M. T. W.) thanks the EaSI-CAT centre for Doctoral Training (MTW) and the EPSRC (EP/T023643/1; KK). The Linz team (L. S., A. E., M. W.) gratefully acknowledges generous financial support by the Austrian Science Funds (FWF) through project No. P31784, the Erasmus+ program and the JKU Linz/Upper Austria scheme. The Madrid team (J. A. F.-S., J. A., R. d. R-R.) gratefully acknowledges the Spanish Government (RTI2018-095038-B-100), “Communidad de Madrid” for European Structural Funds (S2018/NMT-4367) and proyectos sinergicos I + D (Y2020/NMT-6469) for funding. J. A. F.-S. thanks the Spanish government for a Ramón y Cajal contract.The incorporation of the CF2 motif within organic structures is known to affect the susceptibility of functional groups to oxidation, as well as altering conformation and reactivity. In this manuscript, the incorporation of the CF2 functional group within an isothiourea catalyst skeleton to give C(3)-F2-HBTM is reported. Effective gram-scale routes to both racemic and enantiopure heterocyclic Lewis bases are developed, with preliminary catalytic and kinetic activity evaluated.Peer reviewe

Catalyst selective and regiodivergent O- to C- or N-carboxyl transfer of pyrazolyl carbonates: synthetic and computational studies

The regiodivergent O- to C- or N-carboxyl transfer of pyrazolyl carbonates is described, with DMAP giving preferential N-carboxylation and triazolinylidenes promoting selective C-carboxylation (both with up to >99 : 1 regioselectivity). An enantioselective O- to C-carboxyl variant using NHC catalysis is demonstrated (up to 92% ee), while mechanistic and DFT studies outline the pathways operative in this system and provide insight into the reasons for the observed selectivity