α-Hydroxyphosphonic acid derivatives of 2-azanorbornane: synthesis, DFT calculations, and crystal structure analysis

Highly diastereoselective hydrophosphonylation of 2-azanorbornane aldehyde exo-1 with silylated phosphorus esters yielded the (S)-α-hydroxyphosphonic acid exo-3a. The use of endo-2 gives the isomer with the opposite configuration at the new stereogenic center (R)-endo-4a. X-ray analysis revealed that exo-3a crystallizes in the orthorhombic space group P212121 with two crystallographically independent molecules, one zwitterionic and the other forming a salt with HBr.

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endo-((R)-Hydroxy((1S,3S,4R)-2-((S)-1-phenylethyl)-2-azabicyclo[2.2.1]heptan-3-yl)methyl)phosphonic acidC15H22NO4P[α]D20 = +30.0 (c 1.0, H2O)Source of chirality: endo-(1S,3S,4R)-2-((S)-1-phenylethyl)-2-azabicyclo[2.2.1]heptaneAbsolute configuration: (1S,3S,4R,1′S,1″R)

exo-((R)-Hydroxy((1R,3S,4S)-2-((R)-1-phenylethyl)-2-azabicyclo[2.2.1]heptan-3-yl)methyl)phosphonic acidC15H22NO4P[α]D20 = −18.8 (c 1.0, H2O)Source of chirality: exo-(1R,3S,4S)-2-((R)-1-phenylethyl)-2-azabicyclo[2.2.1]heptaneAbsolute configuration: (1R,3S,4S,1′R,1″R)

exo-((S)-Hydroxy((1S,3R,4R)-2-((S)-1-phenylethyl)-2-azabicyclo[2.2.1]heptan-3-yl)methyl)phosphonic acidC15H22NO4P[α]D20 = −19.0 (c 0.8, H2O)Source of chirality: exo-(1S,3R,4R)-2-((S)-1-phenylethyl)-2-azabicyclo[2.2.1]heptaneAbsolute configuration: (1S,3R,4R,1′S,1″S)