Stereogenic P(V) Synthesis via Catalytic Continuous Substitutions DOI

Gaoliang Zheng,

Yuchen Zhang, Jingming Zhang

et al.

Journal of the American Chemical Society, Journal Year: 2025, Volume and Issue: unknown

Published: April 9, 2025

Phosphorus(V) stereocenters that are fully substituted by heteroatoms play important roles in bioactive molecules and organocatalysts. Existing methods to achieve such motifs rely almost entirely on resolution or diastereocontrol, prefunctionalized substrates usually required generate specific P(V) stereocenters. In contrast, related catalytic rare, no generally applicable method is described. Here, we report a modular strategy access broad variety of stereogenic-at-phosphorus skeletons, including ProTide analogs, alkoxylphosphoramidates, phosphates, phosphorothioates, phosphonamidates, through designed enantioselective continuous substitutions simple precursors. The nucleophilic substitution sequence readily determined the stereoconfiguration products. Concise synthesis analogs drug demonstrated practical value protocol. Experimental computational studies unveiled unique π-π stacking effect chalcogen bonding interaction between catalyst substrate as origin stereoselectivity.

Language: Английский

Stereogenic P(V) Synthesis via Catalytic Continuous Substitutions DOI

Gaoliang Zheng,

Yuchen Zhang, Jingming Zhang

et al.

Journal of the American Chemical Society, Journal Year: 2025, Volume and Issue: unknown

Published: April 9, 2025

Phosphorus(V) stereocenters that are fully substituted by heteroatoms play important roles in bioactive molecules and organocatalysts. Existing methods to achieve such motifs rely almost entirely on resolution or diastereocontrol, prefunctionalized substrates usually required generate specific P(V) stereocenters. In contrast, related catalytic rare, no generally applicable method is described. Here, we report a modular strategy access broad variety of stereogenic-at-phosphorus skeletons, including ProTide analogs, alkoxylphosphoramidates, phosphates, phosphorothioates, phosphonamidates, through designed enantioselective continuous substitutions simple precursors. The nucleophilic substitution sequence readily determined the stereoconfiguration products. Concise synthesis analogs drug demonstrated practical value protocol. Experimental computational studies unveiled unique π-π stacking effect chalcogen bonding interaction between catalyst substrate as origin stereoselectivity.

Language: Английский

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