Enantioselective Palladium-Catalyzed Decarboxylative Dearomative Asymmetric Allylic Alkylation of Benzofurans: Diversity-Oriented Synthesis of Flavaglines

With the introduction of new Trost-type bisphosphine ligands bearing a chiral cycloalkane framework, the highly efficient and enantioselective Palladium-catalyzed decarboxylative dearomative asymmetric allylic alkylation (AAA) of benzofurans was achieved. This enabled a diversity-oriented synthesis (DOS) of previously unreachable flavaglines, which features two diversification stages. A new avenue for developing flavagline-based drugs was thus established.

Recent Advances in the Construction of Quaternary Stereocenters via Palladium Catalyzed Decarboxylative Asymmetric Allylic Alkylation

Palladium catalyzed decarboxylative asymmetric allylic alkylation (DAAA) provides an efficient and powerful strategy to construct quaternary stereocenters which are widely present in biologically active natural products and approved drugs. In this short review, we summarize recent developments (since 2018) in the facile synthesis of quaternary stereocenters via DAAA methods. Several representative examples by using DAAA strategy for total synthesis of complex natural products further demonstrate its synthetic potential in the realm of organic and medicinal chemistry

New Nitrogen, Sulfur-, and Selenium-Donating Ligands Derived from Chiral Pyridine Amino Alcohols. Synthesis and Catalytic Activity in Asymmetric Allylic Alkylation

Although many chiral ligands for asymmetric catalysis have been developed, there is still a need for new structures allowing the modular approach. Recently, easy synthesis of chiral pyridine-containing β-amino alcohols has been elaborated by opening respective epoxides with enantiomeric 1-phenylethylamine. This paper reports the synthetic transformation of β-amino alcohols into the new complexing pyridine-containing seleno- and thioethers. The amino alcohols were effectively converted to cyclic sulfonamidates, which were reacted with thiolates or phenyl selenide nucleophile. The reaction was diastereoselective, and its outcome depended on the configuration at the substitution center. The problem was discussed considering DFT optimized structures of both diastereomeric sulfonamidates. New amino-aldimine ligands were also synthesized from chiral pyridine-containing diamines. Nine new chiral ligands were tested in the Tsuji-Trost allylic alkylation resulting in the enantiomerically enriched product in up to 75% ee. The observed stereochemical induction agrees with the prevailing nucleophilic attack at the allylic carbon laying opposite to the complexing nitrogen of pyridine in η3-allylic intermediate complexes.