Highly diastereoselective addition of chiral H-phosphonate to tert-butylsulfinyl aldimines: a convenient approach to (R)-α-aminophosphonic acids

A highly diastereoselective nucleophilic addition of chiral H-phosphonate, derived from a readily available TADDOL auxiliary, to (S)-N-tert-butylsulfinyl aldimines is reported. The reaction proceeds at room temperature in the presence of potassium carbonate and yields the corresponding aliphatic, aromatic and heteroaromatic α-aminophosphonates with dr >95:5. Subsequent simultaneous removal of both chiral auxiliaries leads to the desired α-aminophosphonic acids in very good yields with an (R)-configuration at the stereogenic α carbon.

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(S)-N-((R)-1-((3aR,8aR)-2,2-Dimethyl-6-oxido-4,4,8,8-tetraphenyltetrahydro-[1,3]dioxolo[4,5-e][1,3,2]dioxaphosphepin-6-yl)-2-methylpropyl)-2-methylpropane-2-sulfinamideC39H46NO6PS[α]D20 = −163.0 (c 1.0, CHCl3)Source of chirality: Asymmetric synthesisAbsolute configuration: (1R)

(S)-N-((R)-((3aR,8aR)-2,2-Dimethyl-6-oxido-4,4,8,8-tetraphenyltetrahydro-[1,3]dioxolo[4,5-e][1,3,2]dioxaphosphepin-6-yl)(phenyl)methyl)-2-methylpropane-2-sulfinamideC42H44NO6PS[α]D20 = −122.0 (c 1.0, CHCl3)Source of chirality: Asymmetric synthesisAbsolute configuration: (1R)

(S)-N-((R)-((3aR,8aR)-2,2-Dimethyl-6-oxido-4,4,8,8-tetraphenyltetrahydro-[1,3]dioxolo[4,5-e][1,3,2]dioxaphosphepin-6-yl)(4-fluorophenyl)methyl)-2-methylpropane-2-sulfinamideC42H43FNO6PS[α]D20 = −91.0 (c 1.0, CHCl3)Source of chirality: Asymmetric synthesisAbsolute configuration: (1R)

(S)-N-((R)-((3aR,8aR)-2,2-Dimethyl-6-oxido-4,4,8,8-tetraphenyltetrahydro-[1,3]dioxolo[4,5-e][1,3,2]dioxaphosphepin-6-yl)(thiophen-2-yl)methyl)-2-methylpropane-2-sulfinamideC40H42NO6PS2[α]D20 = −157.0 (c 1.0, CHCl3)Source of chirality: Asymmetric synthesisAbsolute configuration: (1R)