Enantioselective addition of diethylzinc to aldehydes catalyzed by aziridine carbinols

A series of enantiopure aziridine carbinols were synthesized from commercially available starting materials (l-serine and piperonylaldehyde), and characterized by 1H NMR, 13C NMR, HRMS, and IR. Their enantioselective induction behaviors were evaluated as chiral ligands in the asymmetric addition of diethylzinc and phenylethynylzinc to aryl and α,β-unsaturated aldehydes. Chiral aziridine carbinol 1h was found to catalyze the asymmetric addition of diethylzinc to aldehydes at low catalyst loadings (as little as 1 mol %), and the conversion rates were close to quantitative (up to 97% yield) with good to excellent enantiomeric excesses (up to 98% ee). A possible catalytic reaction mechanism is proposed.

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(2S)-1-Piperonylmethylaziridin-2-yl(dimethyl)methanolC13H17NO3[α]D20 = +4.5 (c 0.594, CHCl3)Source of chirality: l-SerineAbsolute configuration: (S)

(2S)-1-Piperonylmethylaziridin-2-yl(di-n-propyl)methanolC17H25NO3[α]D20 = −12.7 (c 1.05, CH2Cl2)Source of chirality: l-SerineAbsolute configuration: (S)

(2S)-1-Piperonylmethylaziridin-2-yl(di-i-propyl)methanolC17H25NO3[α]D20 = −117.1 (c 0.564, CHCl3)Source of chirality: l-SerineAbsolute configuration: (S)

(2S)-1-Piperonylmethylaziridin-2-yl(di-n-butyl)methanolC19H29NO3[α]D20 = −20.2 (c 1.05, CH2Cl2)Source of chirality: l-SerineAbsolute configuration: (S)

(2S)-1-Piperonylmethylaziridin-2-yl(di-i-butyl)methanolC19H29NO3[α]D20 = −61.0 (c 1.05, CH2Cl2)Source of chirality: l-SerineAbsolute configuration: (S)

(2S)-1-Piperonylmethylaziridin-2-yl(di-cyclopropyl)methanolC17H21NO3[α]D20 = −27.2 (c 1.05, CH2Cl2)Source of chirality: l-SerineAbsolute configuration: (S)

(2S)-1-Piperonylmethylaziridin-2-yl(dibenzyl)methanolC25H25NO3[α]D20 = −24.3 (c 1.05, CH2Cl2)Source of chirality: l-SerineAbsolute configuration: (S)

(2S)-1-Piperonylmethylaziridin-2-yl(diphenyl)methanolC23H21NO3[α]D20 = −2.0 (c 1.05, CH2Cl2)Source of chirality: l-SerineAbsolute configuration: (S)