Synthesis and stereochemistry of 1,3,2-oxazaphosphorino[4,3-a]isoquinolines

Abstract

1,3,2-Oxazaphosphorino[4,3-a]isoquinolines 8a,b, 9a,b and 10a were synthesized by the reactions of homocalycotomine 7 with appropriate dichlorophosphorus derivatives, such as phenylphosphonic dichloride, bis(2-chloroethyl)phosphonic dichloride or phosphoryl chloride. In spite of the blocking effect of the connecting isoquinoline ring system, the oxazaphosphorinane moiety exists as a chair–twist equilibrium, where the conformer ratios are strongly dependent on the P-4 configuration and the stereoelectronic properties of the substituents.