Synthesis of a new chiral organocatalyst derived from (S)-proline containing a 1,2,4-triazolyl moiety and its application in the asymmetric aldol reaction. Importance of one molecule of water generated in situ

• Published in: Tetrahedron letters Vol. 60; no. 41; pp. 151128 - 151132
• Main Authors: Sánchez-Antonio, Omar, Juaristi, Eusebio
• Format: Journal Article
• Language: English
• Published: OXFORD Elsevier Ltd 10.10.2019; Elsevier
• Subjects: 1,2,4-Triazolyl moiety; Asymmetric organocatalysis; Chemistry; Chemistry, Organic; Enantioselective aldol reaction; Physical Sciences; Proline hydrazides; Science & Technology; Thiosemicarbazides; 1,2,4-Triazolyl moiety; Enantioselective aldol reaction; Proline hydrazides; Asymmetric organocatalysis; Thiosemicarbazides; PROLINE DERIVATIVES; MANNICH; CATALYSIS; DESIGN; ACID; MICHAEL; AQUEOUS-MEDIA; CONJUGATE
• ISSN: 0040-4039; 1873-3581
• DOI: 10.1016/j.tetlet.2019.151128

[Display omitted] •Novel chiral derivatives of (S)-proline are efficient organocatalysts.•1,2,4-Triazolyl moiety in chiral derivatives of (S)-proline turns out to be critical.•Organocatalyzed enantioselective aldol reaction under solvent-free conditions.•Essential involvement of one water molecule in stereoselective aldol reactions. A simple and efficient preparation of a novel chiral derivative of (S)-proline containing a 1,2,4-triazolyl moiety is described. The high-yielding synthetic protocol includes the use of microwave irradiation to afford new chiral pyrrolidine derivatives in high yield. Our triazolyl-containing heterocycle was evaluated as organocatalyst (10 mol% load, under neat reaction conditions) in the enantioselective aldol reaction between four different types of ketones and a variety of aryl aldehydes. Good results in terms of enantioselectivity and chemical yield were observed under solvent-free reaction conditions and in the absence of any additive. Evidence is provided for the involvement of the water molecule generated upon enamine formation in the transition state of the aldol reaction.