Enantioselective Synthesis of Chiral Propargylic Alcohols Catalyzed by Bifunctional Zinc-Based Complexes

Abstract

This work demonstrates an efficient way to prepare chiral propargylic alcohols by asymmetric addition of terminal Zn-acetylide to aldehydes catalyzed by bifunctional zinc-based complexes. The corresponding products with moderate to good yields and enantioselectivities were obtained in the absence of moisture-sensitive Ti(O ⁱ Pr)₄.

GRAPHICAL ABSTRACT

Keywords:

• Alkyne
• asymmetric addition
• bifunctional complexes
• enantioselectivities

ACKNOWLEDGMENTS

We are grateful to the grants from the National Natural Science Foundation of China (No. 20802046), International S&T Cooperation Program of Jiangsu Province (BZ2010048), the Priority Academic Program Development of Jiangsu Higher Education Institutions, and the Key Laboratory of Organic Synthesis of Jiangsu Province for financial support.

Notes

^a All the reactions were performed under argon at room temperature for 24 h. Alkyne/Me₂Zn/benzaldehyde/ligand 1:1:0.5:0.05.

^b Isolated yield.

^c The enantiomeric excess was determined by chiral HPLC analysis of the corresponding products on a Chiralcel OD-H column.

^d 0.2 mmol Ti(O ⁱ Pr)₄ was used.

^e 1 mmol HMPA was added.

^f 1 mmol DME was added.

^g Reaction was carried out at 0 °C.

^h Reaction was carried out at 60 °C.

^a All the reactions were performed under argon at room temperature for 24 h. Alkyne/Et₂Zn/benzaldehyde/C 1:1:0.5:0.05.

^b Isolated yield.

^c The enantiomeric excess was determined by chiral HPLC analysis of the corresponding products on a Chiralcel OD-H column.

^d The ee in parentheses was determined after simple recrystallization.