Palladium-catalyzed enantioselective rearrangement of dienyl cyclopropanes.

Vinyl cyclopropanes (VCPs) are among the most useful three-carbon building blocks in organic synthesis. They are commonly used as dienophiles in a range of cycloaddition reactions. However, VCP rearrangement has not received much attention since its discovery in 1959. In particular, the enantioselective rearrangement of VCP is synthetically challenging. Herein, we report the first palladium-catalyzed regio- and enantioselective rearrangement of VCPs (dienyl or trienyl cyclopropanes) for the construction of functionalized cyclopentene units in high yields and with excellent enantioselectivities and 100% atom economy. The utility of the current protocol was highlighted by a gram-scale experiment. Moreover, the methodology provides a platform for accessing synthetically useful molecules containing cyclopentanes or cyclopentenes.

Atroposelective Synthesis of N-Arylated Quinoids by Organocatalytic Tandem N-Arylation/Oxidation.

Diarylamines and related scaffolds are ubiquitous atropisomeric chemotypes in biologically active natural products. However, the catalytic asymmetric synthesis of these axially chiral compounds remains largely unexplored. Herein, we report that a BINOL-derived chiral phosphoric acid (CPA) successfully catalyzed the atroposelective coupling of quinone esters and anilines through direct C-N bond formation to afford N-aryl quinone atropisomers with an unprecedented intramolecular N-H-O hydrogen bond within a six-membered ring in good yields and enantioselectivities with the quinone ester as both the electrophile and the oxidant. A gram-scale experiment demonstrated the utility of this synthetic protocol. Moreover, this methodology provides a platform for the synthesis of structurally diverse secondary amine atropisomers by nucleophilic addition.

Enantioselective Synthesis of Nitrogen-Nitrogen Biaryl Atropisomers via Copper-Catalyzed Friedel-Crafts Alkylation Reaction.

Nitrogen-nitrogen bonds containing motifs are ubiquitous in natural products and bioactive compounds. However, the atropisomerism arising from a restricted rotation around an N-N bond is largely overlooked. Here, we describe a method to access the first enantioselective synthesis of N-N biaryl atropisomers via a Cu-bisoxazoline-catalyzed Friedel-Crafts alkylation reaction. A wide range of axially chiral N-N bisazaheterocycle compounds were efficiently prepared in high yields with excellent enantioselectivities via desymmetrization and kinetic resolution. Heating experiments showed that the axially chiral bisazaheterocycle products have high rotational barriers.

Enantioselective Synthesis of Atropisomeric Biaryls by Pd-Catalyzed Asymmetric Buchwald-Hartwig Amination.

N-C Biaryl atropisomers are prevalent in natural products and bioactive drug molecules. However, the enantioselective synthesis of such molecules has not developed significantly. Particularly, the enantioselective synthesis of N-C biaryl atropisomers by stereoselective metal-catalyzed aryl amination remains unprecedented. Herein, a Pd-catalyzed cross-coupling strategy is presented for the synthesis of N-C axially chiral biaryl molecules. A broad spectrum of N-C axially chiral compounds was obtained with excellent enantioselectivities (up to 99 % ee) and good yields (up to 98 %). The practicality of this reaction was validated in the synthesis of useful biological molecules.