Practical asymmetric synthesis of β-hydroxy γ-amino acids via complimentary aldol reactions

• Published in: Tetrahedron Vol. 67; no. 34; pp. 6131 - 6137
• Main Authors: Pandya, Bhaumik A., Dandapani, Sivaraman, Duvall, Jeremy R., Rowley, Ann, Mulrooney, Carol A., Ryba, Troy, Dombrowski, Michael, Harton, Marie, Young, Damian W., Marcaurelle, Lisa A.
• Format: Journal Article
• Language: English
• Published: OXFORD Elsevier Ltd 26.08.2011; Elsevier
• Subjects: Aldehydes; Aldol; Aliphatic compounds; Amino acids; Asymmetric; Asymmetry; Chemical reactivity; Chemistry; Chemistry, Organic; Conversion; Diversity-oriented; Exact sciences and technology; Optimization; Organic chemistry; Physical Sciences; Preparations and properties; Reactivity and mechanisms; Science & Technology; Stereochemistry; Synthesis (chemistry); Tetrahedrons; Utilities; γ-Amino acid; Aldol; Asymmetric; Stereochemistry; Diversity-oriented; γ-Amino acid; REAGENT; ENANTIOSELECTIVE SYNTHESIS; STRATEGY; CONDENSATIONS; BISTRAMIDE; PEPSTATIN; DIVERSITY; ANTI; gamma-Amino acid; Stereoisomer; Chemical reagent; Chiral compound; Optimization; Aldol condensation; Asymmetric synthesis; Aminoacid; Chemical reactivity; Chemical synthesis; Protection; Functional group
• ISSN: 0040-4020; 1464-5416
• DOI: 10.1016/j.tet.2011.06.043

Orthogonally protected chiral β-hydroxy-γ-amino acids can be accessed in >100 g quantities from readily available starting materials and reagents in three to four steps. These chiral synthons contain two adjacent stereocenters along with suitably protected functional groups ( O-TBS, N-Boc) for downstream reactivity. Implementation of two existing aldol technologies allows rapid access to all possible stereoisomers of 1. The guiding principles during reaction optimization were reaction scalability and operational efficiency. Conversion of the amino acids to a variety of chiral building blocks in one to two steps demonstrates their synthetic utility. [Display omitted]