Isomerisation versus carbonylative pathways in the hydroxy-carbonylation, methoxy-carbonylation, and amino-carbonylation of N-tosyl-3-pyrroline

Abstract

The reactivity of N-tosyl-3-pyrroline is significantly lower than that of mono-substituted alkenes in Pd catalysed methoxycarbonylation reactions. For example, most bulky diphosphine/Pd catalysts, including the well-known Pd catalyst derived from 1,2-bis(di-tert-butylphosphino)xylene (DTBPX), were found to give no product at all in the methoxycarbonylation of N-tosyl-3-pyrroline. The competing pathways in methoxycarbonylation of N-methane-sulfonyl-3-pyrroline using Pd/DTBPX were studied using DFT calculations at the B97-D2 level; these show that the coordination of the alkene is unfavourable, and once coordinated, isomerisation is a lower energy pathway that ultimately leads to an alternative product. Experimentally a side product resulting from alkene isomerisation and addition of methanol is formed slowly (if CO is present), and rapidly if CO is not. A less bulky derivative of DTBPX forms the required alkene complex with much lower barriers. A study has been made of the enantioselective carbonylation of N-tosyl-3-pyrroline using water, methanol or aniline as nucleophile. This revealed that there is a range of possible products with most of these initiated by a Pd-catalysed isomerisation of the alkene. Using less bulky members of the Pd/phanephos family of catalysts, it is possible to produce the methoxycarbonylation product from this poorly reactive alkene with reasonably good chemoselectivity and around 80% ee at higher pressures of CO.