Facile Synthesis of Enantiomerically Pure P-Chiral 1-Alkoxy-2,3-dihydrophospholes via Nucleophilic P-N Bond Cleavage of a 1-Phospha-2-azanorbornene

The reactive P-N bond in a racemic mixture of endo-1-phospha-2-azanorbornene (PAN) (R-P/S-P)-endo-1 is readily cleaved with enantiomerically pure lithium alkoxides followed by protonation to afford diastereomeric mixtures of P-chiral 1-alkoxy-2,3-dihydrophosphole derivatives. The isolation of these compounds is rather challenging due to the reversibility of the reaction (elimination of alcohols). However, methylation of the sulfonamide moiety of the intermediate lithium salts and sulfur protection of the phosphorus atom prevent the elimination reaction. The resulting air-stable P-chiral diastereomeric 1-alkoxy-2,3-dihydrophosphole sulfide mixtures can be readily isolated and fully characterized. The diastereomers can be separated by crystallization. The 1-alkoxy-2,3-dihydrophosphole sulfides are readily reduced with Raney nickel to afford phosphorus(III) P-stereogenic 1-alkoxy-2,3-dihydrophospholes with potential use in asymmetric homogeneous transition metal catalysis.

Automated summary

The reactive P-N bond in a racemic mixture of endo-1-phospha-2-azanorbornene (PAN) is cleaved with enantiomerically pure lithium alkoxides and protonation to produce diastereomeric mixtures of P-chiral 1-alkoxy-2,3-dihydrophosphole derivatives. The isolation of these compounds is challenging due to the reversibility of the reaction, but methylation and sulfur protection prevent elimination reaction. The resulting P-chiral diastereomeric 1-alkoxy-2,3-dihydrophosphole sulfide mixtures can be easily separated and characterized, and can be reduced to phosphorus(III) P-stereogenic 1-alkoxy-2,3-dihydrophospholes for use in asymmetric homogeneous transition metal catalysis.