A convenient method for the preparation of chiral phosphonoacetamides and their Horner–Wadsworth–Emmons reaction

Chiral phosphonoacetamides bearing (S)-(α-methylbenzyl)benzylamine, (S,S)-bis(α-methylbenzyl)amine, l-phenylglycine methyl ester and l-phenylglycinol were easily prepared in good yield by means of the Michaelis–Arbuzov reaction of chiral bromoacetamides obtained in quantitative yield, with trimethyl phosphite, which under Horner–Wadsworth–Emmons conditions with several aryl and alkyl aldehydes under Masamune–Roush procedure using LiCl and DBU in THF or toluene gave the corresponding chiral α,β-unsaturated amides. The present procedure is a convenient and efficient methodology for the preparation of phosphonoacetamides and chiral α,β-unsaturated amides in high E-selectivity.

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(S)-2-Bromoacetyl(α-methylbenzyl)benzylamineC17H19BrNOEe >98%[α]D = −115.1 (c 2.8, CHCl3)Source of chirality: chemical reactionAbsolute configuration: (S)

(S)-Methyl 2-(2-bromoacetamide)-2-phenylacetateC11H12BrNO3Ee >98%[α]D = +120.8 (c 1.16, CHCl3)Source of chirality: chemical reactionAbsolute configuration: (S)

(S)-2-(Dimethoxyphosphorylacetyl)(α-methylbenzyl)benzylamineC19H24NO4PEe >98%[α]D = −80.5 (c 2.14, CHCl3)Source of chirality: chemical reactionAbsolute configuration: (S)

(S,S)-2-(Dimethoxyphosphorylacetyl)-bis(α-methylbenzyl)amineC20H26NO4PEe >98%[α]D = −112.3 (c 2.02, CHCl3)Source of chirality: chemical reactionAbsolute configuration: (S,S)

(S)-Methyl 2-[2-(dimethoxyphosphoryl)acetamide]-2-phenylacetateC13H19NO6PEe >98%[α]D = +122.75 (c 1.06, CHCl3)Source of chirality: chemical reactionAbsolute configuration: (S)

(S)-2-(2-Dimethoxyphosphoryl)acetamide-2-phenylethanolC12H19NO5PEe >98%[α]D = +34.5 (c 2.98, CHCl3)Source of chirality: chemical reactionAbsolute configuration: (S)

(S)-2-(2-Diethoxyphosphoryl)acetamide-2-phenylethanolC14H23NO5PEe >98%[α]D = +41.8 (c 2.88, CHCl3)Source of chirality: chemical reactionAbsolute configuration: (S)

(S)-(E)-N-(Cinnamoyl)-(α-methylbenzyl)benzylamineC24H23NOEe >98%[α]D = −182.8 (c 4.80, CHCl3)Source of chirality: chemical reactionAbsolute configuration: (S)-(E)

(S)-(E)-N-(p-Chlorocinnamoyl)-(α-methylbenzyl)benzylamineC24H22ClNOEe >98%[α]D = −170.7 (c 3.03, CHCl3)Source of chirality: chemical reactionAbsolute configuration: (S)-(E)

(S)-(E)-N-(p-Methoxycinnamoyl)-(α-methylbenzyl)benzylamineC25H25NO2Ee >98%[α]D = −185.3 (c 2.42, CHCl3)Source of chirality: chemical reactionAbsolute configuration: (S)-(E)

(S)-(E)-N-(3-tert-Butylacryloyl)-(α-methylbenzyl)benzylamineC22H27NOEe >98%[α]D = −156.3 (c 2.63, CHCl3)Source of chirality: chemical reactionAbsolute configuration: (S)-(E)

(S)-(E)-N-(3-iso-Butylacryloyl)-(α-methylbenzyl)benzylamineC22H27NOEe >98%[α]D = −142.8 (c 2.0, CHCl3)Source of chirality: chemical reactionAbsolute configuration: (S)-(E)

(S,S)-(E)-N-(Cinnamoyl)-bis(α-methylbenzyl)amineC25H25NOEe >98%[α]D = +6.79 (c 3.22, CHCl3)Source of chirality: chemical reactionAbsolute configuration: (S,S)-(E)

(S,S)-(E)-N-(p-Chlorocinnamoyl)-bis(α-methylbenzyl)amineC25H24ClNOEe >98%[α]D = +48.3 (c 3.66, CHCl3)Source of chirality: chemical reactionAbsolute configuration: (S,S)-(E)

(S,S)-(E)-N-(p-Methoxycinnamoyl)-bis(α-methylbenzyl)amineC26H27NO2Ee >98%[α]D = +56.4 (c 3.77, CHCl3)Source of chirality: chemical reactionAbsolute configuration: (S,S)-(E)

(S,S)-(E)-N-(3-tert-Butylacryloyl)-bis(α-methylbenzyl)amineC23H29NOEe >98%[α]D = −170.9 (c 3.64, CHCl3)Source of chirality: chemical reactionAbsolute configuration: (S,S)-(E)

(S,S)-(E)-N-(3-iso-Butylacryloyl)-bis(α-methylbenzyl)amineC23H29NOEe >98%[α]D = −81.7 (c 1.66, CHCl3)Source of chirality: chemical reactionAbsolute configuration: (S,S)-(E)

(S)-(E)-Methyl N-(cinnamoyl))-2-amino-2-phenylacetateC18H17NO3Ee >98%[α]D = +39.9 (c 1.26, CHCl3)Source of chirality: chemical reactionAbsolute configuration: (S)-(E)

(S)-(E)-Methyl N-(p-chlorocinnamoyl)-2-amino-2-phenylacetateC18H16ClNO3Ee >98%[α]D = +69.8 (c 1.1, CHCl3)Source of chirality: chemical reactionAbsolute configuration: (S)-(E)

(S)-(E)-Methyl N-(p-methoxycinnamoyl)-2-amino-2-phenylacetateC19H19NO4Ee >98%[α]D = −2.2 (c 1.1, CHCl3)Source of chirality: chemical reactionAbsolute configuration: (S)-(E)

(S)-(E)-Methyl N-(3-tert-butylacryloyl)-2-amino-2-phenylacetateC16H21NO3Ee >98%[α]D = −1.1 (c 2.8, CHCl3)Source of chirality: chemical reactionAbsolute configuration: (S)-(E)

(S)-(E)-Methyl N-(3-iso-propylacryloyl)-2-amino-2-phenylacetateC15H19NO3Ee >98%[α]D = +0.8 (c 2.37, CHCl3)Source of chirality: chemical reactionAbsolute configuration: (S)-(E)

(S)-(Z)-Methyl N-(3-iso-propylacryloyl)-2-amino-2-phenylacetateC15H19NO3Ee >98%[α]D = +7.2 (1.36, CHCl3)Source of chirality: chemical reactionAbsolute configuration: (S)-(Z)

(S)-(E)-Methyl N-(3-iso-butylacryloyl)-2-amino-2-phenylacetateC16H21NO3Ee >98%[α]D = +86.15 (c 0.78, CHCl3)Source of chirality: chemical reactionAbsolute configuration: (S)-(E)

(S)-(Z)-Methyl N-(3-iso-butylacryloyl)-2-amino-2-phenylacetateC16H21NO3Ee >98%[α]D = +0.1 (c 0.6, CHCl3)Source of chirality: chemical reactionAbsolute configuration: (S)-(Z)

(S)-N-(Cinnamoyl)-2-amino-2-phenylethanolC17H17NO2Ee >98%[α]D = −29.8 (c 2.47, MeOH)Source of chirality: chemical reactionAbsolute configuration: (S)-(E)

(S)-N-(p-Chlorocinnamoyl)-2-amino-2-phenylethanolC17H16ClNO2Ee >98%[α]D = −51.1 (c 2.1, MeOH)Source of chirality: chemical reactionAbsolute configuration: (S)-(E)

(S)-N-(p-Methoxycinnamoyl)-2-amino-2-phenylethanolC18H19NO3Ee >98%[α]D = −71.4 (c 2.6, MeOH)Source of chirality: chemical reactionAbsolute configuration: (S)-(E)

(S)-(E)-N-(3-tert-Butylacryloyl)-2-amino-2-phenylethanolC15H21NO2Ee >98%[α]D = +97.5 (c 2.74, MeOH)Source of chirality: chemical reactionAbsolute configuration: (S)-(E)

(S)-(E)-N-(3-iso-Butylacryloyl)-2-amino-2-phenylethanolC14H19NO2Ee >98%[α]D = +66.2 (c 0.95, CHCl3)Source of chirality: chemical reactionAbsolute configuration: (S)-(E)

(S)-(E)-N-(3-iso-Propylacryloyl)-2-amino-2-phenylethanolC15H21NO2Ee >98%[α]D = +75.8 (c 2.45, CHCl3)Source of chirality: chemical reactionAbsolute configuration: (S)-(E)