Work

Urea Ligand‐Promoted Chainwalking Heteroannulation for the Synthesis of 6‐ and 7‐membered Azaheterocycles

Year: 2024

Type: article

Abstract: Typical approaches to heterocycle construction require significant changes in synthetic strategy even for a change as minor as increasing the ring size. The ability to access multiple heterocyclic scaffolds through a common synthetic approach, simply through trivial modification of one reaction component, would enable facile access to diverse libraries of structural analogues of core scaffolds. Here, we show that urea-derived ligands effectively promote Pd-mediated chainwalking processes to enable remote heteroannulation for the rapid construction of six- and seven-membered azaheterocycles under essentially identical reaction conditions. This method demonstrates good functional group tolerance and effectively engages sterically hindered substrates. In addition, this reaction is applicable to target-oriented synthesis, demonstrated through the formal synthesis of antimalarial alkaloid galipinine.

Source: Chemistry - A European Journal

DOI: 10.1002/chem.202402587

Authors: Owen E. Monteferrante, Kaitlyn E. Houghtling, Aidan R. Kropiwnicki, Shauna M. Paradine

Institution: University of Rochester

Language: English

Topic: Catalytic Cross-Coupling Reactions

Subfield: Organic Chemistry

Field: Chemistry

Domain: Physical Sciences

Open Access status: bronze

Funder: National Science Foundation

Awards: MRI: Acquisition of a CryoProbe 500 MHz Nuclear Magnetic Resonance (NMR) Spectrometer, CAREER: Establishing Ligand Platforms to Enable Selective, Catalytic Olefin Difunctionalization Reactions for Constructing Diverse Heterocyclic Scaffolds