Kenny, Miles and Schröder, Sybrin and Taylor, Nicholas and Jackson, Paula and Kitson, Daniel and Franckevicius, Vilius (2018) Palladium-Catalysed Construction of All-Carbon Quaternary Centres with Propargylic Electrophiles : Challenges in the Simultaneous Control of Regio-, Chemo- and Enantioselectivity. SYNTHESIS, 50 (9). pp. 1796-1814. ISSN 0039-7881
Franckevicius_Synthesis_Accepted.pdf - Accepted Version
Available under License Creative Commons Attribution-NonCommercial.
Download (11MB)
Abstract
This article describes the palladium-catalysed three-component coupling of 1,3-dicarbonyl compounds with nucleophiles and propargylic electrophiles for the generation of quaternary all-carbon centres in a single step, which necessitates the simultaneous control of regio-, chemo- and enantioselectivity. The use of propargyl enol carbonates, the source of two of the components, was found to be essential in maintaining high levels of regiocontrol and chemoselectivity, whereas a careful analysis of pKa trends of O-, C- and N-nucleophiles as the other coupling partner indicates that the highest levels of selectivity are likely to be obtained with relatively acidic species, such as phenols, 1,3-dicarbonyl compounds and aromatic N-heterocycles. Finally, studies towards the development of the catalytic enantioselective construction of quaternary all-carbon centres by means of alkenylation and allylic alkylation are disclosed.