Synthesis of quinazolinone-based aziridine diols as chiral ligands: dual stereoselectivity in the asymmetric ethylation of aryl aldehydes. Issue 2 (15th February 2015)

• Record Type: Journal Article
• Authors: Celik, Saffet; Cakici, Murat; Kilic, Hamdullah; Sahin, Ertan
• Is Part Of: Tetrahedron, asymmetry. Volume 26:Issue 2/3(2015)
• Page Start: 152
• Page End: 157
• Publication Date: 2015-02-15
• Subjects: Asymmetry (Chemistry) -- Periodicals; 547.005
• DOI: 10.1016/j.tetasy.2014.12.011
• Languages: English
• ISSNs: 0957-4166

Abstract

Graphical abstract: Abstract: A new class of quinazoline-based enantiomerically pure aziridine diols4a –d were prepared from the aziridination of mesityl oxide3 with in situ generated 3-acetoxyaminoquinazolinone ( S )-2b followed by NaBH4 reduction. Aziridine diols4a –d were purified by means of column chromatography on silica gel and their stereochemistries were assigned by X-ray crystallography and NMR analysis. These aziridine diols4 were evaluated as chiral ligands in the asymmetric addition of diethylzinc to aryl aldehydes, and ligand ( S, R, R )-4a yielded ( R )-1-phenylpropanol derivatives with up to 92% ee, while the diastereomer ( S, S, R )-4c gave the opposite enantiomers ( S )-1-phenylpropanol derivatives with up to 86% ee. The results demonstrate that switching the configuration of the aziridine alcohol moiety in ligand gives a remarkable reversal of enantioselectivity in the asymmetric addition of diethylzinc to aryl aldehydes. Abstract : 3-[(3 R )-3-Acetyl-2, 2-dimethylaziridin-1-yl]-2-[(1 S )-1-hydroxyethyl]quinazolin-4(3 H )-one: C16 H19 N3 O3 Ee: 99% Source of chirality: ( S )-Lactic acid Absolute configuration: ( R, S ) [ α ]D 20 = −16 ( c 1, DCM) Abstract : 3-[(3 S )-3-Acetyl-2, 2-dimethylaziridin-1-yl]-2-[(1 S )-1-hydroxyethyl]quinazolin-4(3 H )-one: C16 H19 N3 O3 Ee: 99% Source of chirality: ( S )-Lactic acid Absolute configuration: ( S, S ) [ α ]D 20 = +73 ( c 1, DCM) Abstract : 2-[(1 S )-1-Hydroxyethyl]-3-{(3 R )-3-[(1 R )-1-hydroxyethyl]-2, 2-dimethylaziridin-1-yl}quinazolin-4(3 H )-one: C16 H21 N3 O3 Ee: 99% Source of chirality: ( S )-Lactic acid Absolute configuration: ( S, R, R ) [ α ]D 20 = −103 ( c 1, DCM) Abstract : 2-[(1 S )-1-Hydroxyethyl]-3-{(3 R )-3-[(1 S )-1-hydroxyethyl]-2, 2-dimethylaziridin-1-yl}quinazolin-4(3 H )-one: C16 H21 N3 O3 Ee: 99% Source of chirality: ( S )-Lactic acid Absolute configuration: ( S, R, S ) [ α ]D 20 = −192 ( c 1, DCM) Abstract : 2-[(1 S )-1-Hydroxyethyl]-3-{(3 S )-3-[(1 R )-1-hydroxyethyl]-2, 2-dimethylaziridin-1-yl}quinazolin-4(3 H )-one: C16 H21 N3 O3 Ee: 99% Source of chirality: ( S )-Lactic acid Absolute configuration: ( S, S, R ) [ α ]D 20 = +240 ( c 1, DCM) Abstract : 2-[(1 S )-1-Hydroxyethyl]-3-{(3 S )-3-[(1 S )-1-hydroxyethyl]-2, 2-dimethylaziridin-1-yl}quinazolin-4(3 H )-one: C16 H21 N3 O3 Ee: 99% Source of chirality: ( S )-Lactic acid Absolute configuration: ( S, S, S ) [ α ]D 20 = +126 ( c 1, DCM) Abstract : (1 S )-1-{3-[(3 R )-3-Acetyl-2, 2-dimethylaziridin-1-yl]-4-oxo-3, 4-dihydroquinazolin-2-yl}ethyl 4-nitrobenzoate: C23 H22 N4 O6 Ee: 99% Source of chirality: ( S )-Lactic acid Absolute configuration: ( S, R ) [ α ]D 20 = +220 ( c 1, DCM)