A new approach to the utilization of highly reactive and unstable ortho-quinone methides (o-QMs) in catalytic asymmetric settings is presented. The enantioselective reactions are catalysed by bifunctional organocatalysts, and the o-QM intermediates are formed in situ from 2-sulfonylalkyl phenols through base-promoted elimination of sulfinic acid. The use of mild Brønsted basic conditions for transiently generating o-QMs in catalytic asymmetric processes is unprecedented, and allows engaging productively in the reactions nucleophiles such as Meldrum's acid, malononitrile and 1,3-dicarbonyls. The catalytic transformations give new and general entries to 3,4-dihydrocoumarins, 4H-chromenes and xanthenones. These frameworks are recurring structures in natural product and medicinal chemistry, as testified by the formal syntheses of (R)-tolterodine and (S)-4-methoxydalbergione from the catalytic adducts.

The first stereoselective synthesis of enantioenriched axially chiral indole-quinoline systems is presented. The strategy takes advantage of an organocatalytic enantioselective Povarov cycloadditiono f3 -alkenylindoles and N-arylimines, followed by an oxidative central-to-axial chirality conversion process, allowing for access to previously unre-porteda xially chiral indole-quinoline biaryls. The methodology is also implementedf or the design and the preparation of challengingc ompounds exhibitingt wo stereogenic axes. DFT calculations shed light on the stereoselectivityo ft he central-to-axial chirality conversion,s howing unconventional behavior.Scheme1.Combining organocatalytice nantioselective Povarovc ycloadditions with the oxidative central-to-axial chirality conversion concept.

Nonbiaryl atropisomers are molecules defined by a stereogenic axis featuring at least one nonarene moiety. Among these, scaffolds bearing a conformationally stable C­(sp2)–C­(sp3) stereogenic axis have been observed in natural compounds; however, their enantioselective synthesis remains almost completely unexplored. Herein we disclose a new class of chiral C­(sp2)–C­(sp3) atropisomers obtained with high levels of stereoselectivity (up to 99% ee) by means of an organocatalytic asymmetric methodology. Multiple molecular motifs could be embedded in this class of C­(sp2)–C­(sp3) atropisomers, showing a broad and general protocol. Experimental data provide strong evidence of the conformational stability of the C­(sp2)–C­(sp3) stereogenic axis (up to t 1/2 25 °C >1000 y) in the obtained compounds and show kinetic control over this rare stereogenic element. This, coupled with density functional theory calculations, suggests that the observed stereoselectivity arises from a Curtin–Hammett scenario establishing an equilibrium of intermediates. Furthermore, the experimental investigation led to evidence of the operating principle of central-to-axial chirality conversions.

The development of novel and effective metal-free catalytic systems, which can drive value-added organic transformations in environmentally benign solvents (for instance, water), is highly desirable. Moreover, these new catalysts need to be harmless, easy-to-prepare, and potentially recyclable. In this context, amine-rich carbon dots (CDs) have recently emerged as promising nano-catalytic platforms. These nitrogen-doped nanoparticles, which show dimensions smaller than 10 nm, generally consist of carbon cores that are surrounded by shells containing numerous amino groups. In recent years, organic chemists have used these surface amines to guide the design of several synthetic methodologies under mild operative conditions. This Concept highlights the recent advances in the synthesis of amine-rich carbon dots and their applications in organic catalysis, including forward-looking opportunities within this research field.

A novel strategy for the direct enantioselective oxidative homocoupling of α-branched aldehydes is presented. The methodology employs open-shell intermediates for the construction of chiral 1,4-dialdehydes by forming a carbon-carbon bond connecting two quaternary stereogenic centers in good yields and excellent stereoselectivities for electron-rich aromatic aldehydes. The 1,4-dialdehydes were transformed into synthetically valuable chiral pyrrolidines. Experimental mechanistic investigations based on competition experiments combined with computational studies indicate that the reaction proceeds through a radical cation intermediate and that reactivity and stereoselectivity follow different trends.