Enantioselective Synthesis of Oxazocines via MQ-Phos Enabled Palladium-Catalyzed Asymmetric Formal [4+4]-Cycloadditions.

Oxazocines are key structural intermediates in the synthesis of natural products and pharmaceutical molecules. However, the synthesis of oxazocines especially in a highly enantioselective manner, is a long-standing formidable challenge due to unfavorable energetics involved in cyclization. Herein, a series of new PNP-Ligand P-chiral stereocenter is first designed and synthesized, called MQ-Phos, and successfully applied it in the Pd-catalyzed enantioselective higher-order formal [4+4]-cycloaddition of α, ß-unsaturated imines with 2-(hydroxymethyl)-1-arylallyl carbonates. The reaction features mild conditions, excellent regio- and enantiocontrol and a broad substrate scope (54 examples). Various medium-sized rings can be afforded in moderate to excellent yields (up to 92%) and excellent enantioselectivity (up to 99% ee). The newly developed MQ-Phos is critical for synthesis of the medium-sized ring in excellent catalytic reactivity and enantioselectivity.

Rigid P-Chiral Phosphorus Ligands for Highly Selective Palladium-Catalyzed (4+2) and (4+4) Annulations.

We developed novel shackled P-chiral ligands based on 1-phosphanorbornenes and oxazolines. They were subsequently evaluated in palladium-catalyzed (4+2) annulations, producing enantioenriched tetrahydropyran scaffolds in good yields with high site selectivity and enantioselectivity. Moreover, chemoselective (4+4) products were also achieved by using acyclic imines. In addition, density functional theory calculations were performed to afford the energy profile of the Michael addition step and ring formation step. This demonstrated that the enantioselective (4+2) annulations and the chemoselective reaction between (4+2) and (4+4) products were mostly under thermodynamic control.

Recent Advances in Lewis Base-Catalysed Chemo-, Diastereo- and Enantiodivergent Reactions of Electron-Deficient Olefins and Alkynes.

Lewis base catalysis provides powerful synthetic strategies for the selective construction of carbon-carbon and carbon-heteroatom bonds. Thus continuous efforts have been deployed to develop effective methodologies involving Lewis base catalysis. The nucleophilicity and steric hindrance of Lewis base catalyst often plays a major role in catalytic reactivity and selectivity in the reaction. In the past decades, tremendous progress has been made in the divergent construction of valuable motifs under Lewis base catalysis. In this review, we provide a comprehensive and updated summary of Lewis base-catalysed chemo-, diastereo- and enantiodivergent reaction, as well as the related mechanism will be highlighted in detail.

A Palladium-Catalyzed Monodearoylative Dimerization Approach for the Synthesis of [3]Dendralenes.

On treatment with Pd(OAc)2 and K2CO3, a variety of 3-aryl-2-(2-bromoallyl)-1,3-dicarbonyl compounds went through a monodearoylative dimerization reaction to provide polysubstituted [3]dendralenes in moderate to good isolated yields.

Synthesis of 5-Amino and 3,5-Diamino Substituted 1,2,4-Thiadiazoles by I2-Mediated Oxidative N-S Bond Formation.

An oxidative N-S bond formation reaction has been established for 1,2,4-thiadiazole synthesis employing molecular iodine as the sole oxidant. The features of the present reaction include no use of transition metals, mild reaction conditions, simple operation, and short reaction time. This versatile synthetic approach is broadly applicable to a variety of imidoyl and guanyl thiourea substrates to produce 5-amino and 3,5-diamino substituted 1,2,4-thiadiazole derivatives, respectively, in an efficient and scalable fashion.

Synthesis of 2-Cyclopentenone Derivatives via Palladium-Catalyzed Intramolecular Carbonyl α-Alkenylation.

2-Cyclopentenone derivatives have been efficiently synthesized from 5-bromo-5-hexen-2-ones via palladium-catalyzed intramolecular carbonyl α-alkenylation followed by double-bond migration under mild reaction conditions.