Maksim Osipov

Palladium-Catalyzed Dynamic Kinetic Asymmetric Transformations of Vinyl Aziridines with Nitrogen Heterocycles: Rapid Access to Biologically Active Pyrroles and Indoles

We report that nitrogen heterocycles can serve as competent nucleophiles in the palladium-catalyzed dynamic kinetic asymmetric alkylation of vinyl aziridines. The resulting alkylated products were obtained with high regio-, chemo-, and enantioselectivity. Both substituted 1H-pyrroles and 1H-indoles were successfully employed to give exclusively the branched N-alkylated products. The synthetic utility of this process was demonstrated by applying this method to the preparation of several medicinal chemistry lead compounds and bromopyrrole alkaloids including longamide B, longamide B methyl ester, hanishin, agesamides A and B, and cyclooroidin.

Palladium‐Catalyzed Asymmetric Construction of Vicinal All‐Carbon Quaternary Stereocenters and its Application to the Synthesis of Cyclotryptamine Alkaloids

We report the use of a two-fold Pd-catalyzed decarboxylative allylic alkylation (Pd-DAAA) to construct two vicinal all carbon quaternary stereocenters in a diastereo- and enantioselective fashion. To demonstrate the synthetic utility of this process, the products of the Pd-DAAA were elaborated to complete the formal syntheses of the cyclotryptamine alkaloids. Mechanistic investigations have revealed that the two-fold Pd-catalyzed transformation proceeds through an initial matched first allylation followed by a second mismatched allylation to deliver the desired product.

Recent Advances on the Total Syntheses of Communesin Alkaloids and Perophoramidine

The communesin alkaloids are a diverse family of Penicillium-derived alkaloids. Their caged-polycyclic structure and intriguing biological profiles have made these natural products attractive targets for total synthesis. Similarly, the ascidian-derived alkaloid, perophoramidine, is structurally related to the communesins and has also become a popular target for total synthesis. This review serves to summarize the many elegant approaches that have been developed to access the communesin alkaloids and perophoramidine. Likewise, strategies to access the communesin ring system are reviewed.

A new class of non-C2-symmetric ligands for oxidative and redox-neutral palladium-catalyzed asymmetric allylic alkylations of 1,3-diketones.

We report the discovery, synthesis, and application of a new class of non-C2-symmetric phosphoramidite ligands derived from pyroglutamic acid for use in both oxidative and redox-neutral palladium-catalyzed asymmetric allylic alkylations of 1,3-diketones. The resulting chiral products are typically obtained in high yield with good to excellent levels of enantioselectivity.

Acetoxy Meldrum's acid: a versatile acyl anion equivalent in the Pd-catalyzed asymmetric allylic alkylation.

Acetoxy Meldrums acid can serve as a versatile acyl anion equivalent in the Pd-catalyzed asymmetric allylic alkylation. The reaction of this nucleophile with various meso and racemic electrophiles afforded alkylated products in high yields and enantiopurities. These enantioenriched products are versatile intermediates that can be further functionalized using nitrogen- and oxygen-centered nucleophiles, affording versatile scaffolds for the synthesis of nucleoside analogues. These scaffolds were used to complete formal syntheses of the anti-HIV drugs carbovir, abacavir, and the antibiotic aristeromycin.

A Concise Enantioselective Synthesis of (−)-Ranirestat

A concise, enantioselective synthesis of the potent aldose reductase inhibitor ranirestat (1) is reported. The synthesis was accomplished employing inexpensive, commercially available starting materials. A palladium-catalyzed asymmetric allylic alkylation (Pd-AAA) of malonate 4 was utilized as a key transformation to construct the tetrasubstituted chiral center in the target.

Palladium-catalyzed asymmetric allylic alkylation of electron-deficient pyrroles with meso electrophiles.

Pyrroles can serve as competent nucleophiles with meso electrophiles in the Pd-catalyzed asymmetric allylic alkylation. The products from this transformation were obtained as a single regio- and diastereomer in high yield and enantiopurity. A nitropyrrole-containing nucleoside analogue was synthesized in seven steps to demonstrate the synthetic utility of this transformation.