A copper-catalyzed umpolung of N-2,2,2-trifluoroethylisatin ketimines for the enantioselective 1,3-dipolar cycloaddition with benzo­[b]­thiophene sulfones was developed. Using a catalyst system consisting of an (S,Sp )- t Bu-Phosferrox ligand, Cu­(OTf)2, and Cs2CO3, a range of pentacyclic spirooxindoles containing pyrrolidine and benzo­[b]­sulfolane subunits were obtained in high efficiency with excellent regio-, diastereo-, and enantioselectivites under mild conditions. The practicality and versatility of the reaction were also demonstrated.

Elansolid A is a structurally complex polyketide macrolactone natural product that exhibits promising antibacterial properties. Its challenging asymmetric total synthesis was achieved by a convergent strategy, in which the tetrahydroindane core of the molecule and an eastern vinyl iodide moiety were combined as the main fragments. The central tetrahydroindane motif was constructed with high stereoselectivity by a bioinspired intramolecular Diels− Alder cycloaddition, generating four stereogenic centers in a single step. The stereocontrol of this key step could be achieved by virtue of a 1,3-allylic strain generated by the temporary introduction of a steric-directing iodine substituent on the substrate. The formation of the macrolactone motif that completes the synthesis was achieved via two different retrosynthetic disconnections, namely, a Suzuki−Miyaura cross-coupling or an alternative Mukaiyama esterification reaction.

The installation of deuterium atoms at distal C(sp 3 )−H bonds is a longstanding synthetic challenge. Through the synergistic combination of chain-walking strategy and transfer hydrodeuteration, we present the remote transfer hydrodeuteration of unactivated alkenes at distal C(sp 3 )−H sites, aided by native directing groups, using readily available pinacolborane (HBpin) and D 2 O as H − and D + sources, respectively. Significantly, this tactic offers a complementary pattern to conventional hydrodeuteration methods that adduct H−D, or its surrogate, to unsaturated bonds. Both experimental data and density functional theory (DFT) studies demonstrated the critical role of the directing group in guiding the olefin isomerization process. DFT calculations suggest that it was the in situ-generated Ni(II)− hydride rather than Ni(I)−hydride that performed as active intermediates in the olefin insertion and isomerization steps.

An unprecedented cascade strategy consisting of piperidine-promoted polarity reversal, normal electron-demand Diels–Alder cycloaddition and skeletal remodeling was developed to construct structurally novel pyridine-fused nitrones in up to 82% yield.

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