王飞

A general asymmetric route for the one-step synthesis of chiral β-branched amides is reported through the highly enantioselective isomerization of allylamines, followed by enamine exchange, and subsequent oxidation. The enamine exchange allows for a rapid and modular synthesis of various amides, including challenging β-diaryl and β-cyclic.

A domino process: A Rh^I/chiral BINAP catalysis is reported for the one-step modular synthesis of chiral β-branched amides with various amine nucleophiles. β-dialkyl, β-diaryl, and β-alkylaryl stereocenters are established under identical conditions with excellent enantio- and diastereoselectivity in a ligand-controlled manner.

A method for the decarboxylative macrocyclization of peptides bearing N-terminal Michael acceptors has been developed. This synthetic method enables the efficient synthesis of cyclic peptides containing γ-amino acids and is tolerant of functionalities present in both natural and non-proteinogenic amino acids. Linear precursors ranging from 3 to 15 amino acids cyclize effectively under this photoredox method. To demonstrate the preparative utility of this method in the context of bioactive molecules, we synthesized COR-005, a somatostatin analogue that is currently in clinical trials.

Oh, take me back to the start: A method for the decarboxylative macrocyclization of peptides bearing N-terminal Michael acceptors was developed. This photoredox method enables the efficient synthesis of cyclic peptides containing γ-amino acids, is tolerant of functionalities present in natural amino acids. Linear precursors ranging from 3 to 15 amino acids can be effectively cyclized by using this method.

The first enantioselective total synthesis of (−)-cycloclavine was accomplished in 8 steps and 7.1 % overall yield. Key features include the first catalytic asymmetric cyclopropanation of allene, mediated by the dirhodium catalyst Rh₂(S-TBPTTL)₄, and the enone 1,2-addition of a new TEMPO carbamate methyl carbanion. An intramolecular strain-promoted Diels–Alder methylenecyclopropane (IMDAMC) reaction provided a pivotal tricyclic enone intermediate with more than 99 % ee after crystallization. The synthesis of (−)-1 was completed by a late-stage intramolecular Diels–Alder furan (IMDAF) cycloaddition to install the indole.

Ringing the changes: An enantioselective total synthesis of (−)-cycloclavine was accomplished in 8 steps and 7.1 % overall yield. Key features include the use of unsubstituted allene in a transition-metal-mediated enantioselective cyclopropanation to deliver a methylenecyclopropane (MCP). This transformation gives direct and atom-economical access to MCPs and could be further expanded for the synthesis of diverse “spring-loaded” reagents in organic synthesis.