Practical synthesis of enantiomerically pure β2-amino acids via proline-catalyzed diastereoselective aminomethylation of aldehydes

Yonggui Chi, Emily P. English, William C. Pomerantz, W. Seth Horne, Leo A. Joyce, Lane R. Alexander, William S. Fleming, Elizabeth A. Hopkins, Samuel H. Gellman

Research output: Contribution to journalArticle

54 Citations (Scopus)

Abstract

Proline-catalyzed diastereoselective aminomethylation of aldehydes using a chiral iminium ion, generated from a readily prepared precursor, provides α-substituted-β-amino aldehydes with 85:15 to 90: 10 dr. The α-substituted-β-amino aldehydes can be reduced to β-substituted-γ-amino alcohols, the major diastereomer of which can be isolated via crystallization or column chromatography. The amino alcohols are efficiently transformed to protected β2-amino acids, which are valuable building blocks for β-peptides, natural products, and other interesting molecules. Because conditions for the aminomethylation and subsequent reactions are mild, β2-amino acid derivatives with protected functional groups in the side chain, such as β2- homoglutamic acid, β2-homotyrosine, and β2- homolysine, can be prepared in this way. The synthetic route is short, and purifications are simple; therefore, this method enables the preparation of protected β2-amino acids in useful quantities.

Original languageEnglish (US)
Pages (from-to)6050-6055
Number of pages6
JournalJournal of the American Chemical Society
Volume129
Issue number18
DOIs
StatePublished - May 9 2007

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Aldehydes
Proline
Amino alcohols
Amino Alcohols
Amino acids
Amino Acids
Column chromatography
Crystallization
Biological Products
Functional groups
Peptides
Purification
Chromatography
Ions
Derivatives
Molecules
Acids

Cite this

Practical synthesis of enantiomerically pure β2-amino acids via proline-catalyzed diastereoselective aminomethylation of aldehydes. / Chi, Yonggui; English, Emily P.; Pomerantz, William C.; Horne, W. Seth; Joyce, Leo A.; Alexander, Lane R.; Fleming, William S.; Hopkins, Elizabeth A.; Gellman, Samuel H.

In: Journal of the American Chemical Society, Vol. 129, No. 18, 09.05.2007, p. 6050-6055.

Research output: Contribution to journalArticle

Chi, Yonggui ; English, Emily P. ; Pomerantz, William C. ; Horne, W. Seth ; Joyce, Leo A. ; Alexander, Lane R. ; Fleming, William S. ; Hopkins, Elizabeth A. ; Gellman, Samuel H. / Practical synthesis of enantiomerically pure β2-amino acids via proline-catalyzed diastereoselective aminomethylation of aldehydes. In: Journal of the American Chemical Society. 2007 ; Vol. 129, No. 18. pp. 6050-6055.
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