Continuous Flow as Enabling Technology: Synthesis of Heteroaromatic Sulfinates as Bench Stable Cross-Coupling Partners.

An enabling continuous flow setup for handling of unstable organolithium intermediates and synthesis of heteroaryl sulfinates on a multigram scale is described. The developed continuous flow process allows for the synthesis and simple isolation of heteroaryl sulfinates which are otherwise challenging to access in classical batch mode. The lithium sulfinate salts prepared by this method were shown to be efficient reaction partners in palladium catalyzed C(sp2)-C(sp2) cross-coupling to access medicinally relevant bis-heteroaryl motifs.

C-H functionalisation of aldehydes using light generated, non-stabilised diazo compounds in flow.

The difficulty in accessing and safely utilising non-stabilised diazo species has in the past limited the application of this class of compounds. Here we explore further the use of oxadiazolines, non-stabilised diazo precursors which are bench stable, in direct, non-catalytic, aldehyde C-H functionalisation reactions under UV photolysis in flow and free from additives. Commercially available aldehydes are coupled to afford unsymmetrical aryl-alkyl and alkyl-alkyl ketones while mild conditions and lack of transition metal catalysts allow for exceptional functional group tolerance. Examples are given on small scale and in a larger scale continuous production.

A Versatile Route to Unstable Diazo Compounds via Oxadiazolines and their Use in Aryl-Alkyl Cross-Coupling Reactions.

Coupling of readily available boronic acids and diazo compounds has emerged recently as a powerful metal-free carbon-carbon bond forming method. However, the difficulty in forming the unstable diazo compound partner in a mild fashion has hitherto limited their general use and the scope of the transformation. Here, we report the application of oxadiazolines as precursors for the generation of an unstable family of diazo compounds using flow UV photolysis and their first use in divergent protodeboronative and oxidative C(sp2 )-C(sp3 ) cross-coupling processes, with excellent functional-group tolerance.

Visible-Light-Mediated Annulation of Electron-Rich Alkenes and Nitrogen-Centered Radicals from N-Sulfonylallylamines: Construction of Chloromethylated Pyrrolidine Derivatives.

A visible-light-mediated annulation of N-sulfonylallylamines and olefins is reported. Rapid access to highly functionalized chloromethylated pyrrolidines can be achieved using mild conditions for the generation of nitrogen-centered radicals. Both a transition-metal-based catalyst and an organic dye can be used as photosensitizers with 0.5 mol % loading. The reaction was found to be applicable to a large variety of electron-rich and electron-neutral olefins.

Organocatalytic asymmetric synthesis of polyfunctionalized 3-(cyclohexenylmethyl)-indoles via a quadruple domino Friedel-Crafts-type/Michael/Michael/aldol condensation reaction.

A new organocatalytic quadruple domino Friedel-Crafts-type/Michael/Michael/aldol condensation reaction has been developed. In this one-pot multi-component process acrolein, various indoles and nitroalkenes are used as starting materials. The diphenylprolinol TMS-ether catalysis provides a straightforward and efficient entry to 3-(cyclohexenylmethyl)-indoles bearing three stereogenic centers in moderate to excellent yields (23-82%) and excellent stereoselectivities (dr = 91 : 9 to >95 : 5, ee = 94 to >99%).