This short review highlights select examples of enantioselective Lewis base promoted reactions that use tertiary amine (cinchona alkaloids, isothioureas, and DMAP/PPY derivatives) or NHC catalysts and employ aryloxide-promoted catalyst turnover from an acyl ammonium or azolium intermediate. This review focuses on the range of strategies that have been developed within this area, and discusses their evolution and context.1 Introduction2 Phenols as Additives To Promote Catalyst Turnover2.1 NHC Catalysis with α-Functionalised Aldehydes and Phenols2.2 Enantioselective Fluorination with Aryloxide-Promoted Catalyst Turnover3 In Situ Catalytic Generation Of Aryloxide3.1 Aryloxide-Promoted Turnover Generated from an Electrophilic Polyhalogenated Quinone: Overview3.2 Aryloxide-Promoted Catalyst Turnover Generated from an α-Aryl­oxyaldehyde or Aryl Ester Starting Material: Overview4 Summary and Outlook

We report a photochemical method for the functionalization of pyridines with radicals derived from allylic C−H bonds. Overall, two substrates undergo C−H functionalization to form a new C(sp 2 )−C(sp 3 ) bond. The chemistry harnesses the unique reactivity of pyridinyl radicals, generated upon single-electron reduction of pyridinium ions, which undergo effective coupling with allylic radicals. This novel mechanism enables distinct positional selectivity for pyridine functionalization that diverges from classical Minisci chemistry. Crucial was the identification of a dithiophosphoric acid that masters three catalytic tasks, sequentially acting as a Brønsted acid for pyridine protonation, a single electron transfer (SET) reductant for pyridinium ion reduction, and a hydrogen atom abstractor for the activation of allylic C(sp 3 )−H bonds. The resulting pyridinyl and allylic radicals then couple with high regioselectivity.

We report a catalytic asymmetric protocol for the preparation of chiral pyrrolidinones proceeding via a radical pathway. The chemistry exploits the combination of photoredox catalysis and Lewis base catalysis to realise the first example of asymmetric radical conjugate addition to α,β-unsaturated anhydrides and esters. The reaction is initiated by photoredox activation of Narylglycines to generate, upon decarboxylation, α-amino radicals. These radicals are then intercepted stereoselectively by α,β-unsaturated acyl ammonium intermediates, whose formation is mastered by a chiral isothiourea organocatalyst. Cyclisation leads to catalyst turnover and formation of enantioenriched pyrrolidinones. The utility of the protocol was demonstrated with application to the synthesis of biologically-active γamino butyric acids.

Enantioselective [2 + 2] cycloaddition of C(1)ammonium enolates generated catalytically using the isothiourea HyperBTM with N-alkyl isatins gives spirocyclic β-lactones. In situ ring opening with an amine nucleophile generates isolable highly enantioenriched products in up to 92:8 dr and in >99:1 er.β-Lactones are versatile synthetic building blocks and significant components of many bioactive natural products. 1,2 As a consequence, a range of enantioselective synthetic methods for their preparation has been developed, with both Lewis acid and Lewis base catalyzed approaches common. 3 In terms of Lewis base catalysis using tertiary amines, the use of cinchona alkaloids and chiral DMAP derivatives has been extensively used to promote β-lactone formation through the generation of an intermediate C(1)-ammonium enolate. 4 Although versatile, these methods typically rely on the generation of reactive monosubstituted ketenes (formed in situ from acyl chlorides) or isolable but sensitive disubstituted ketenes as starting materials. 5 In an alternative approach, Romo introduced the NCAL (nucleophile-catalyzed aldollactonization) process to prepare β-lactones from keto-acids (Scheme 1a). 6 Key to this protocol was the development of carboxylic acids as the C(1)-ammonium enolate precursor, with a modified Mukaiyama reagent used for in situ generation of a reactive ester. Addition of either a cinchona alkaloid or isothiourea catalyst was used to generate the desired C(1)ammonium enolate, with subsequent intramolecular formal [2 + 2]-cycloaddition onto the pendant carbonyl giving highly enantioenriched β-lactones. Building on this work, we previously demonstrated the use of symmetric arylacetic anhydrides as alternative C(1)-ammonium enolate precursors. 7 These anhydrides are generally readily prepared from the parent carboxylic acid, are easy to handle, and can be used in conjunction with isothiourea catalysts without requiring the excess base that is a recognized limitation of alternative protocols using carboxylic acids as starting materials. This approach was applied to the HyperBTM-catalyzed enantioselective intermolecular formation of β-lactones with perfluoroalkyl ketones and arylacetic anhydrides (Scheme 1b). Mechanistic studies using natural abundance 13 C kinetic isotope effect experiments, together with computational analyses, indicated the operation of a concerted asynchronous

The catalytic generation of C(1)-ammonium enolates from the corresponding α-silyl-α-alkyl substituted carboxylic acids using the isothiourea HyperBTM is reported. This desilylative approach grants access to α-unsubstituted and α-alkyl substituted C(1)-ammonium enolates, which are typically difficult to access through traditional methods reliant upon deprotonation. The scope and limitations of this process is established in enantioselective [2+2]-cycloaddition processes with perfluoroalkylketones (31 examples, up to 96 % yield and > 99 : 1 er), as well as selective [2+2]-cycloaddition with trifluoromethyl enones (4 examples, up to 75 % yield and > 99 : 1 er). Preliminary mechanistic studies indicate this process proceeds through an initial kinetic resolution of an in situ prepared (�)-α-silyl-α-alkyl substituted anhydride, while the reaction process exhibits overall pseudo zero-order kinetics.