Enantioselective Addition of Diethylzinc to Aromatic Aldehydes Catalyzed by Pyrolidine and Piperidine β-Amino Alcohols

Abstract

The enantioselective alkylation of aryl aldehydes by diethylzinc in the presence of catalytic amounts of several chiral pyrolidine- and piperidine-based amino alcohol ligands, synthesized from the reaction of (R)-2-amino-1-butanol and (S)-2-amino-3-phenylpropan-1-ol with appropriate dibromoalkanes, was studied. The influence of temperature and ligand structure has been investigated. Addition of diethylzinc to aromatic aldehydes under the optimized condition gave the corresponding products in excellent yields with ee values of up to 77%.

Keywords:

• Aldehydes
• β-amino alcohols
• diethylzinc
• enantioselectivity

ACKNOWLEDGMENTS

Financial support from the Research Council of Shahid Beheshti University and Catalyst Center of Excellence (CCE) is gratefully acknowledged.

Notes

^a GC yield of the mixture of the two enantiomers.

^b Ee was determined by GC using a chiral capillary column (HP-Chiral).

^c Absolute configuration of the major enantiomer was determined by comparison with authentic sample.

^d With 120 mol% of Ti(OPr ⁱ )₄.

^a Condition: 10°C, 40 h, and 10 mol% of 6.

^b Measured as conversion % by GC.

^c Determined by capillary chiral GC analysis using the chiral column (HP-chiral).

^d Absolute configuration was determined by comparing the sign of specific rotation.^[ 16-19 ^]

The major enantiomer in all cases had the R configuration.

^e Values in parentheses are for condition of −30°C, 40 h, and 20 mol% of 6.