Light‐Driven Enantioselective Organocatalytic β‐Benzylation of Enals

Abstract

A photochemical organocatalytic strategy for the direct enantioselective β‐benzylation of α,β‐unsaturated aldehydes is reported. The chemistry capitalizes upon the light‐triggered enolization of 2‐alkyl‐benzophenones to afford hydroxy‐o‐quinodinomethanes. These fleeting intermediates are stereoselectively intercepted by chiral iminium ions, transiently formed upon condensation of a secondary amine catalyst with enals. Density functional theory (DFT) studies provided an explanation for why the reaction proceeds through an unconventional Michael‐type addition manifold, instead of a classical cycloaddition mechanism and subsequent ring‐opening.

Enantioselective Synthesis of Aminodiols by Sequential Rhodium‐Catalysed Oxyamination/Kinetic Resolution: Expanding the Substrate Scope of Amidine‐Based Catalysis

“…Computational chemistry has indeed demonstrated to be very convenient to construct useful models to understand the factors that affect organocatalytic reactions, in terms of the chemo‐, regio‐ or enantioselectivity . Specifically, DFT has been a widely used method in organocatalytic processes, such as in cycloadditions, iodine(III)‐mediated reactions and photo‐organocatalysis …”

Iminium and enamine catalysis in enantioselective photochemical reactions

“… 13 More recently, Melchiorre, Maseras and co-workers discovered an enantioselective Michael-type addition reaction of photogenerated ortho -quinodimethanes to enals in the presence of a chiral secondary amine. 14 Using 20 mol% of diphenylprolinol tert -butyldimethylsilylether ( 1 ) and 20 mol% of diphenylphosphoric acid (DPP), benzophenones 9 reacted with aliphatic enals ( e.g. , 10a–10f ) smoothly in 1,2-dichlorobenzene upon irradiation at λ = 365 nm with a 15 W black light bulb to afford solely the β-benzylated products 11a–11f in moderate yields with good to excellent enantioselectivity ( Scheme 2 ).…”

Organocatálise Enantiosseletiva: Evolução E Aspectos Recentes

“…32 Recentemente, Maseras e Melchiorre demonstraram que íons imínio podem interceptar hidroxi-o-quinodinometanos gerados por enolização fotoquímica de benzofenonas 26 de forma enantiosseletiva (Esquema 8). 33 Dessa forma, foi possível realizar a β-benzilação de aldeídos 27, cujos exemplos relatados na literatura são escassos.…”