Pd-Catalyzed Sequential Electrophilic Cyclization/Selective C-H Annulation Cascade: Synthesis of Isoxazole-Phthalimide-Fused Poly-Heterocyclics.

Harnessing the organo-palladium intermediates generated from electrophilic cyclizations for tandem C-C bond construction is a challenging task but constitutes an excellent tool for constructing complex motifs from simpler substrates. We realize herein such a cyclative annulation of alkynyl-oxime ethers with maleimides for the facile construction of isoxazole-phthalimide hybrid motifs through Pd(II) catalysis. This protocol features excellent regio-selectivity in C-H selection, a broad substrate scope, good functional group tolerance, and scalability.

Pd-catalyzed regioselective rollover dual C-H annulation cascade: facile approach to phenanthrene derivatives.

Annulations of unsaturated systems through C-H activation represent a powerful tool for producing multicyclic scaffolds. Having coordinating centers in both annulation partners (a dual coordination strategy) would afford remarkable selectivities in the outcomes. Along this concept, we report herein a Pd-catalyzed regioselective rollover cascade dual C-H annulation of -arylphenols with alkynols for constructing phenanthrene scaffolds.

Synthetic and Medicinal Chemistry Approaches Toward WEE1 Kinase Inhibitors and Its Degraders.

WEE1 is a checkpoint kinase critical for mitotic events, especially in cell maturation and DNA repair. Most cancer cells' progression and survival are linked with elevated levels of WEE1 kinase. Thus, WEE1 kinase has become a new promising druggable target.

Development of 2-chloroquinoline based heterocyclic frameworks as dual inhibitors of SARS-CoV-2 M and PL.

Evolution of new variants of SARS-CoV-2 warrant the need for the continued efforts in identifying target-oriented new drugs. Dual targeting agents against M and PL not only overcome the incomplete efficacy but also the drug resistance, which is common problem. Since both these are cysteine proteases, we designed 2-chloroquinoline based molecules with additional imine moiety in the middle as possible nucleophilic warheads.

Propargyl Alcohols as Bifunctional Reagents for Divergent Annulations of Biphenylamines via Dual C-H Functionalization/Dual Oxidative Cyclization.

The C-H functionalization strategy provides access to valuable molecules that previously required convoluted synthetic attempts. Dual C-H unsymmetrical functionalization, with a single bifunctional reagent, is an effective tactic. Propargyl alcohols (PAs), despite containing a reactive C≡C bond, have not been explored as building blocks via oxidative cleavage.

Rhodium-Catalyzed Annulation of Phenacyl Ammonium Salts with Propargylic Alcohols via a Sequential Dual C-H and a C-C Bond Activation: Modular Entry to Diverse Isochromenones.

Given their omnipresence in natural products and pharmaceuticals, isochromenone congeners are one of the most privileged scaffolds to synthetic chemists. Disclosed herein is a dual (/) C-H and C-C activation of phenacyl ammonium salts (acylammonium as traceless directing group) toward annulation with propargylic alcohols to accomplish rapid access for novel isochromenones by means of rhodium catalysis from readily available starting materials. This operationally simple protocol features broad substrate scope and wide functional group tolerance.