Hydrogen-Bond Catalyst Grants Access to Diverse Scope of Enantioenriched Stereogenic-at-P(V) Building Blocks

Key words

hydrogen-bond-donor catalysis - desymmetrization - stereogenic phosphorus - stereospecific displacement

Significance

Forbes and Jacobsen report a hydrogen-bond-donor-catalyzed desymmetrization of arylphosphonic dichlorides to give enantioenriched chlorophosphonamidate intermediates, and their stereospecific transformations to furnish a variety of building blocks that are stereogenic at a P(V) atom. Use of a commercially available urea-based organocatalyst gave the corresponding products in generally good yields and with excellent enantiomeric ratios.

Comment

Whereas enantioenriched stereo­genic-at-P(V) compounds have emerged as crucial building blocks in medicinal chemistry, their enantioselective synthesis has typically relied on the use of chiral auxiliaries. The authors contribute a broadly applicable method and prove its synthetic potential with the synthesis of known biologically active compounds.