Stereochemistry of cycloaddition of (S)-N-(1-phenylethyl)-C-diethoxyphosphorylated nitrone with vinyl acetate. Studies on mutarotation of 3-(O,O-diethylphosphoryl)-5-hydroxyisoxazolidines

Three enantiomerically pure diethyl 5-acetoxy-2-[(S)-1-phenylethyl]isoxazolidinyl-3-phosphonates were obtained by 1,3-dipolar cycloaddition of the title nitrone and vinyl acetate. Each of them was subsequently transformed into the respective 5-hydroxy derivatives, which exist as equilibrium mixtures of C5-anomers. Detailed mutarotation studies on a 3-(O,O-diethylphosphoryl)-5-hydroxyisoxazolidine system showed that trans-isomer (3S,5R) is favoured in the solid state, whereas after 48 h in chloroform-d solution it epimerises at C5 to an (89:11) equilibrium mixture of (3S,5S)- and (3S,5R)-isomer. The major (3S,5S)-anomer adopts a single E3 conformation, which is stabilised by the C3–P(O)⋯HO–C5 hydrogen bond. Absolute configurations of the cycloadducts were established based on conformational analysis employing 1H, 13C and 31P NMR data and confirmed by the transformation of the (3S,5R)-isomer into the known (S)-(+)-phosphohomoserine.

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Diethyl (3S,5R)-5-acetoxy-2-[(S)-1-phenylethyl]isoxazolidinyl-3-phosphonateC17H26NO6PEe = 100%[α]D20=-128.1 (c 1.4, CHCl3)Source of chirality: (S)-1-phenylethylamineAbsolute configuration: (3S,5R,1′S)

Diethyl (3R,5S)-5-acetoxy-2-[(S)-1-phenylethyl]isoxazolidinyl-3-phosphonateC17H26NO6PEe = 100%[α]D20=-17.8 (c 1.2, CHCl3)Source of chirality: (S)-1-phenylethylamineAbsolute configuration: (3R,5S,1′S)

Diethyl (3R,5R)-5-acetoxy-2-[(S)-1-phenylethyl]isoxazolidinyl-3-phosphonateC17H26NO6PEe = 100%[α]D20=-107.5 (c 0.9, CHCl3)Source of chirality: (S)-1-phenylethylamineAbsolute configuration: (3R,5R,1′S)

(3S,5R)-5-Hydroxy-2-((S)-1-phenylethyl)isoxazolidinyl-3-phosphonateC15H24NO5PEe = 100%[α]D20=-71.5 (c 1.4, CHCl3)Source of chirality: (S)-1-phenylethylamineAbsolute configuration: (3S,5R,1′S)

(2S,3S)-2-Ethoxy-2-oxo-3-{N-hydroxy-N-[(S)-1-phenylethyl]amino}-1,2-oxaphospholaneC13H20NO4PEe = 100%[α]D20=-18.1 (c 1.1, CHCl3)Source of chirality: (S)-1-phenylethylamineAbsolute configuration: (2S,3S,1′S)

(2S,3S)-2-Ethoxy-2-oxo-3-{N-acetoxy-N-[(S)-1-phenylethyl]amino}-1,2-oxaphospholaneC15H22NO5PEe = 100%[α]D20=-5.2 (c 0.9, CHCl3)Source of chirality: (S)-1-phenylethylamineAbsolute configuration: (2S,3S,1′S)

tert-Butyl (2S,3S)-2-ethoxy-2-oxo-1,2-oxaphospholan-3-ylcarbamateC14H27N4O7PEe = 100%[α]D20=-33.8 (c 0.9, CHCl3)Source of chirality: (S)-1-phenylethylamineAbsolute configuration: (2S,3S)