Asymmetric synthesis of α-hydroxymethylphosphonates and phosphonic acids via hydrophosphonylation of aldehydes with chiral H-phosphonate

Diastereoselective hydrophosphonylation of aldehydes with a chiral H-phosphonate is described. High asymmetric inductions were obtained using a readily available TADDOL auxiliary. Subsequent, racemization-free removal of the chiral auxiliary led to the desired α-hydroxyphosphonic acids in very good yields and high enantiomeric purity as the (R)-enantiomers.

Figure optionsDownload as PowerPoint slide

(3aR,8aR)-6-((R)-1-Hydroxypropyl)-2,2-dimethyl-4,4,8,8-tetraphenyltetrahydro-[1,3]dioxolo[4,5-e][1,3,2]dioxaphosphepine 6-oxideC34H35O6P[α]D20 = −112.0 (c 1.0, CHCl3)Source of chirality: ((4R,5R)-2,2-dimethyl-1,3-dioxolane-4,5-diyl)bis(diphenylmethanol)Absolute configuration: (3aR,8aR)(R)

(3aR,8aR)-6-((R)-Hydroxy(phenyl)methyl)-2,2-dimethyl-4,4,8,8-tetraphenyltetrahydro-[1,3]dioxolo[4,5-e][1,3,2]dioxaphosphepine 6-oxideC38H35O6P[α]D20 = −114.0 (c 1.0, CHCl3)Source of chirality: ((4R,5R)-2,2-dimethyl-1,3-dioxolane-4,5-diyl)bis(diphenylmethanol)Absolute configuration: (3aR,8aR)(R)