N- to C-sulfonyl photoisomerisation of dihydropyridinones : a synthetic and mechanistic study

The authors thank the European Research Council under the European Union’s Seventh Framework Programme (FP7/2007–2013) ERC Grant Agreement no. 279850 (CF and JET) and EPSRC grant number EP/J018139/1 (DSBD) for funding. ADS thanks the Royal Society for a Wolfson Research Merit Award.The scope and limitations of a photoinitiated N- to C-sulfonyl migration process within a range of dihydropyridinones is assessed. This sulfonyl transfer proceeds without erosion of either diastereo- or enantiocontrol, and is general across a range of N-sulfonyl substituents (SO2R; R = Ph, 4-MeC6H4, 4-MeOC6H4, 4-NO2C6H4, Me, Et) as well as C(3)-(aryl, heteroaryl, alkyl and alkenyl) and C(4)-(aryl and ester) substitution. Crossover reactions indicate an intermolecular step is operative within the formal migration process, although no crossover from C-sulfonyl products was observed. EPR studies indicate the intermediacy of a sulfonyl radical and a mechanism is proposed based upon these observations.Publisher PDFPeer reviewe

A scalable, chromatography-free synthesis of benzotetramisole

The authors thank the Royal Society for a University Research Fellowship (ADS), the EPSRC (EP/J018139/1, DSBD), and GSK (Case award to SRS) for funding. They also thank the European Research Council under the European Union’s Seventh Framework Programme (FP7/2007-2013) ERC grant agreement number 279850 for additional funding, and the EPSRC UK National Mass Spectrometry Service Centre at Swansea University.The scalable, chromatography-free synthesis of the chiral isothiourea benzotetramisole (BTM) in two steps from commercially available materials is presented. A detailed procedure for the synthesis of both enantiomers and the racemate on ca. 10 gram scale is disclosed.PostprintPeer reviewe

Asymmetric isothiourea-catalysed formal [3+2] cycloadditions of ammonium enolates with oxaziridines

The authors thank the Royal Society for a University Research Fellowship (A.D.S.) and the European Research Council under the European Union’s Seventh Framework Programme (FP7/2007—2013), ERC Grant Agreement No. 279850 (C.F. and J.E.T.), GSK (CASE award to S.R.S.) and EPSRC grant No. EP/J018139/1 (D.S.B.D.) for funding.A highly enantioselective Lewis base-catalysed formal [3+2] cycloaddition of ammonium enolates and oxaziridines to give stereodefined oxazolidin-4-ones in high yield is described. Employing an enantioenriched oxaziridine in this process leads to a matched/mis-matched effect with the isothiourea catalyst and allowed the synthesis of either syn- or anti-stereodefined oxazolidin-4-ones in high dr, yield and ee. Additionally, the oxazolidin-4-one products have been derivatised to afford functionalised enantioenriched building blocks.Publisher PDFPeer reviewe

Exploring the scope of the isothiourea-mediated synthesis of dihydropyridinones

The exploration and expansion of the scope of the isothiourea-mediated synthesis of dihydropyridinones is presented. The use of ketimines derived from α,β-unsaturated γ-ketoesters as the Michael acceptor in a Michael addition / lactamisation cascade gives access to a range of dihydropyridinones with high enantioselectivity. The nature of the N-sulfonyl group present on the ketimine is extensively investigated, with further studies into derivatisation of the dihydropyridinone core also reported