Catalytic Asymmetric (3 + 3) Cycloaddition of Oxyallyl Zwitterions with α-Diazomethylphosphonates

Abstract

The unique structure of oxyallyls represents a significant challenge for their catalytic asymmetric applications. Herein, an unprecedented chiral imidodiphosphoric acid-catalytic enantioselective (3 + 3) cycloaddition between oxyallyl zwitterions generated in situ from α-haloketones and α-diazomethylphosphonates was developed. Pharmaceutically interesting chiral pyridazine-4(1H)-ones were obtained in up to 98% yields with excellent stereoselectivities (up to 99% ee, > 99:1 dr).

Development of Cyanopyridazine Derivatives as Photoredox Catalysts and Evaluation of their Catalytic Performance

“…Compared with benzene and pyridine analogues, pyridazine, containing two adjacent sp 2 N atoms, is a stronger electron acceptor and also a more polar compound. Our group has realized the asymmetric (3+3) cycloaddition reaction of oxyallyl zwitterions with α‐diazomethylphosphonates and has accessed a pyridazine‐4(1H)‐one scaffold (Scheme 1b) [9a] . Cycloaddition reactions employing diazoacetates as N ‐terminal electrophiles have also been developed [9b–f] …”

Highly Enantioselective Synthesis of [1,2,4]Triazino[5,4-a]isoquinoline Derivatives via (3 + 3) Cycloaddition Reactions of Diazo Compounds and Isoquinolinium Methylides

“…Diazo compounds, which are stable 1,3-dipoles, have also been used in asymmetric (3 + 2) cycloaddition reactions with dipolarophiles . However, few asymmetric (3 + 3) cycloaddition reactions of diazo compounds with other 1,3-dipoles have been reported . We envisioned that if the asymmetric (3 + 3) cycloaddition reaction of isoquinolinium methylides with diazo compounds could be realized, a series of chiral [1,2,4]­triazino­[5,4- a ]­isoquinoline derivatives would be available easily.…”

“…In alignment with our ongoing interest in the chemistry of α-(diazomethyl)­phosphonate and intrigue in the chiral phosphoryl heteropolycyclic compounds, − ,,, we surmised that bifunctional chiral phase-transfer catalysts (PTCs) containing a hydrogen bond could enable interactions with the substrate via electrostatic attraction accompanied by a hydrogen bond interaction and achieve control of the reaction stereoselectivity . In this study, we developed a method for synthesizing chiral [1,2,4]­triazino­[5,4- a ]­isoquinoline derivatives via unprecedented asymmetric (3 + 3) cycloaddition reactions of diazo compounds with a methyl isoquinoline ylide.…”