Stereoselective total synthesis of (+)-radicamine B via anti,syn,syn-oxazine

The stereoselective total synthesis of (+)-radicamine B was achieved using commercially available d-4-hydroxy-phenylglycine via chiral 1,3-oxazine, which has been applied to synthesis of amino polyols such as DAB-1, d-fagomine, and phytosphingosines. The key steps in this strategy were the palladium(0)-catalyzed stereoselective intramolecular oxazine formation, an extension of the chirality of anti,syn-oxazine with Lewis acid and vinylmagnesium bromide, and pyrrolidine ring formation via hydrogenation reaction. The chiral extension is also applicable to other chiral 1,3-oxazine derived from d-4-hydroxy-phenylglycine.

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(R)-N-(2-(Methoxy-(methyl)amino)-1-(4-nnethoxyphenyl)-2-oxoethyl)benzannideC18H20N2O4[α]D25 = −115.3 (c 0.1, CHCl3)Source of chirality: d-4-hydroxyphenyl glycineAbsolute configuration: (R)

(R,E)-N-(5-Chloro-1-(4-methoxyphenyl)-2-oxopent-3-enyl)benzamideC19H18CINO3[α]D25 = −191.7 (c 0.1,CHCl3)Source of chirality: d-4-hydroxyphenyl glycineAbsolute configuration: (R)

N-((1R,2S,E)-5-Chloro-2-hydroxy-1-(4-methoxyphenyl)pent-3-enyl)benzamideC19H2OCINO3[α]D25 = −45.7 (c 0.1,CHCl3)Source of chirality: d-4-hydroxyphenyl glycine and asymmetric synthesisAbsolute configuration: 1-(R),2-(S)

N-((1R,2S,E)-2-(tert-Butyldimethylsilyloxy)-5-chloro-1-(4-methoxyphenyl)pent-3-enyl)benzamideC25H34CINO3Si[α]D25 = −46.9 (c 0.1, CHCl3)Source of chirality: d-4-hydroxyphenyl glycineand asymmetric synthesisAbsolute configuration: 1-(R),2-(S)

(4R,5R,6R)-5-(tert-Butyldimethylsilyloxy)-4-(4-methoxyphenyl)-2-phenyl-6-vinyl-5,6-dihydro-4H,3-oxazineC25H33NO3Si[α]D25 = −8.0 (c 0.1, CHCl3)Source of chirality: d-4-hydroxyphenyl glycineand asymmetric synthesisAbsolute configuration: 4-(R),5-(R),6-(R)

(S)-(4R,5R,6R)-5-(tert-Butyldimethylsilyloxy)-4-(4-methoxyphenyl)-2-phenyl-5,6-dihydro-4H-1,3-oxazin-6-yl)prop-2-en-1-olC26H35NO4Si[α]D25 = +5.1 (c 0.1, CHCl3)Source of chirality: d-4-hydroxyphenyl glycine and asymmetric synthesisAbsolute configuration: 1-(S)-1-(4R,5R,6R)

(R)-1-((4R,5R,6R)-5-(tert-Butyldimethylsilyloxy)-4-(4-methoxyphenyl)-2-phenyl-5,6-dihydro-4H-1,3-oxazin-6-yl)prop-2-en-1-olC26H35NO4Si[α]D25 = +30.3 (c 0.4, CHCl3)Source of chirality: d-4-hydroxyphenyl glycineand asymmetric synthesisAbsolute configuration: 1-(S)-1-(4R,5R,6R)

(S)-1-((4R,5R,6S)-5-(tert-Butyldimethylsilyloxy)-4-(4-methoxyphenyl)-2-phenyl-5,6-dihydro-4H-1,3-oxazin-6-yl)-2-hydroxyethyl methanesulfonateC26H37NO7SSi[α]D25 = +28.5 (c 0.3, CHCl3)Source of chirality: d-4-hydroxyphenyl glycineand asymmetric synthesisAbsolute configuration: 1-(S)-1-(4R,5R,6R)

(2R,3R,4R,5R)-4-(tert-Butyldimethylsilyloxy)-2-(hydroxymethyl)-5-(4-methoxyphenyl)pyrrolidin-3-olC18H31NO4Si[α]D25 = +7.6 (c 0.1,CHCl3)Source of chirality: d-4-hydroxyphenyl glycine and asymmetric synthesisAbsolute configuration: 2-(R)-3-(R)-4-(R)-5-(R)

(2R,3R,4R,5R)-4-(Hydroxy)-2-(hydroxymethyl)-5-(4-hydroxyphenyl)pyrrolidin-3-olC11H15NO4[α]D25 = +42.8 (c 0.04, MeOH)Source of chirality: d-4-hydroxyphenyl glycine and asymmetric synthesisAbsolute configuration: 2-(R)-3-(R)-4-(R)-5-(R)