New fast and practical method for the enantioselective synthesis of α-vinyl, α-alkyl quaternary α-amino acids

We describe a fast and practical enantioselective synthesis of (S)-N-Cbz-α-vinyl, phenylalanine, suitable for the preparation of different N-Cbz-α-vinyl aminoacids of both configurations. The new protocol exploits a Wittig reaction on highly enantiomeric enriched N-Cbz-α-formyl-α-alkyl amino esters, readily accessible from (l)-serine through a stereoselective alkylation of Seebach’s oxazolidine, carried out with a significant improvement of the previously reported method. The synthetic scheme is suitable for gram scale preparation of the desired product with a 94% ee.

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(S)-Methyl 2-benzyl-2-(benzyloxycarbonylamino)-3-hydroxypropanoateC19H21NO5Ee >94%[α]D = −70.0 (c 1.9, CHCl3, 23 °C)Source of chirality: asymmetric synthesisAbsolute configuration: (S)

(S)-Methyl 2-benzyl-2-(benzyloxycarbonylamino)-3-oxopropanoateC19H19NO5Ee >94%[α]D = −16.1 (c 0.9, CDCl3, 23 °C)Source of chirality: asymmetric synthesisAbsolute configuration: (S)

(S)-Methyl 2-benzyl-2-(benzyloxycarbonylamino)but-3-enoateC20H21NO4Ee >94%[α]D = −37.6 (c 1.1, CDCl3, 23 °C)Source of chirality: asymmetric synthesisAbsolute configuration: (S)

(S)-2-Benzyl-2-(benzyloxycarbonylamino)but-3-enoic acidC19H19NO4Ee = 94%[α]D = −30.9 (c 1.0, CDCl3, 23 °C)Source of chirality: asymmetric synthesisAbsolute configuration: (S)

(S)-Methyl 2-(benzyloxycarbonylamino)-2-methyl-3-oxopropanoateC13H15NO5Ee >94%[α]D = −19.2 (c 1.0, CDCl3, 23 °C)Source of chirality: asymmetric synthesisAbsolute configuration: (S)

(S)-Methyl 2-(benzyloxycarbonylamino)-2-methylbut-3-enoateC14H17NO4Ee >94%[α]D = +3.5 (c 1.7, CDCl3, 23 °C)Source of chirality: asymmetric synthesisAbsolute configuration: (S)

(S)-2-(Benzyloxycarbonylamino)-2-methylbut-3-enoic acidC13H15NO4Ee = 94%[α]D = +7.2 (c 1.0, CDCl3, 23 °C)Source of chirality: asymmetric synthesisAbsolute configuration: (S)

(S)-Methyl 2-amino-2-(hydroxymethyl)pent-4-enoateC7H13NO3Ee >94%[α]D = +2.3 (c 1.7, CHCl3, 23 °C)Source of chirality: asymmetric synthesisAbsolute configuration: (S)

(S)-Methyl 2-(benzyloxycarbonylamino)-2-(hydroxymethyl)pent-4-enoateC15H19NO5Ee >94%[α]D = −2.1 (c 0.5, CHCl3, 23 °C)Source of chirality: asymmetric synthesisAbsolute configuration: (S)

(S)-Methyl 2-(benzyloxycarbonylamino)-2-formylpent-4-enoateC15H17NO5Ee >94%[α]D = −17.8 (c 0.5, CHCl3, 23 °C)Source of chirality: asymmetric synthesisAbsolute configuration: (S)

(S)-Methyl 2-(benzyloxycarbonylamino)-2-vinylpent-4-enoateC16H19NO4Ee >94%[α]D = −17.6 (c 0.8, CHCl3, 23 °C)Source of chirality: asymmetric synthesisAbsolute configuration: (S)

(S)-2-(Benzyloxycarbonylamino)-2-vinylpent-4-enoic acidC15H17NO4Ee = 94%[α]D = −7.5 (c 0.4, CHCl3, 23 °C)Source of chirality: asymmetric synthesisAbsolute configuration: (S)