Modular Prolinol Chiral Ligands for Enantioselective Addition of Diethylzinc to Aromatic Aldehydes

Abstract

Enantioselective addition of diethylzinc (ZnEt₂) to a series of aromatic aldehydes was promoted using a modular prolinol chiral ligand, 2-(S)-2-(hydroxydiphenylmethyl)pyrrolidin-1-yl)methyl)-4-nitrophenol (1a), without using titanium complex. The catalytic system employing 15 mol% of 1a was found to promote the addition of diethylzinc to a wide range of aromatic aldehydes with electron-donating and electron-withdrawing substituents, giving up to 86% ee of the corresponding secondary alcohol under mild conditions.

GRAPHICAL ABSTRACT

Keywords:

• Addition reaction
• aldehyde
• C₁-symmetric
• diethylzinc
• prolinol

ACKNOWLEDGMENT

The authors gratefully acknowledge the Open Fund (No. PLN1105) of Key Laboratory of Oil and Gas Reservoir Geology and Exploitation (Southwest Petroleum University) for financial support.

Notes

^a Conditions: concentration of 2a, 0.25 M; Et₂Zn: 1.5 equiv. in hexane solution.

^b Isolated yields.

^c The ee was determined with a chiral GC G-TA column, and the (S or R)-configuration was confirmed by comparison with the reported configuration.^{[ 11 a,b]}

^d Et₂Zn: 1.5 equiv. in PhCH₃. For details, see the Experimental section.

^a Conditions: solvent: PhCH₃; Et₂Zn–hexane solution, similar to Table 1, entry 12.

^b Isolated yields.

^c The ee was determined with a chiral GC G-TA column, and the (S)-configuration was confirmed by comparison with the reported configuration.^{[ 11 a,b]}

^a Conditions: solvent: PhCH₃; 0 °C; concentration of 2: 0.25 M; Et₂Zn in hexane solution. The procedure is the same as in Table 1, entry 12.

^b Isolated yields.

^c The ee was determined with a chiral GC G-TA column, and the (S)-configuration was confirmed by comparison with the reported configuration.^{[ 11 a–c]}

^d The ee was determined using a chiral OD-H or OD column.^{[ 8 a–d]}

^e The ee was determined using a chiral OJ-H column.^{[ 11 f–g]}