Asymmetric Synthesis of β‑Hydroxy-α-amino Phosphonic Acid Derivatives via Organocatalytic Direct Aldol Reaction of α‑Isothiocyanato Phosphonates with Aldehydes

α-Isothiocyanato
phosphonates are first used as nucleophiles
to react with aldehydes for the asymmetric synthesis of β-hydroxy-α-amino
phosphonic acid derivatives. The process is catalyzed by a quinine-derived
thiourea via cascade aldol/cyclization reaction, affording a wide
range of protected β-hydroxy-α-amino phosphonates containing
adjacent quaternary-tertiary stereocenters in up to 93% yield, up
to 81% ee, and >99:1 dr. This work represents the first example
of
α-isothiocyanato phosphonates serving as nucleophiles that are
used in the catalytic asymmetric synthesis.