Preparation of new chiral bisoxazoline ligands for the catalytic asymmetric intramolecular cyclopropanation of α-diazo-β-keto phenyl sulfone to afford a useful bicyclo[3.1.0]hexane derivative

Herein we describe the preparation of novel chiral bisoxazoline ligands with various substituents at the bisoxazoline linkage, for use in the catalytic asymmetric intramolecular cyclopropanation (CAIMCP) of α-diazo-β-keto phenyl-5-hexenyl sulfone to afford a simple, but useful, bicyclo[3.1.0]hexane derivative. The enantioselectivity of the CAIMCP of α-diazo-β-keto phenyl-5-hexenyl sulfone was improved and a product with 84% ee was obtained using 30 mol % of the catalyst, which was prepared in situ by CuOTf and the new bisoxazoline ligand with two 3,5-di-tert-butylbenzyl groups at the bisoxazoline linkage. The product was obtained in enantiomerically pure form by a single crystallization, enabling its use as a chiral building block.

Figure optionsDownload as PowerPoint slide

(S)-2-(1,3-Dicyclohexyl-2-((S)-4,5-dihydro-4-isopropyloxazol-2-yl)propan-2-yl)-4,5-dihydro-4-isopropyloxazoleC27H46N2O2[α]D20=-88.0 (c 0.55, MeOH)Source of chirality: l-valinolAbsolute configuration: (S,S)

(S)-4,5-Dihydro-2-(3-((S)-4,5-dihydro-4-isopropyloxazol-2-yl)-1,5-diphenylpentan-3-yl)-4-isopropyloxazoleC29H38N2O2[α]D20=-64.4 (c 0.55, MeOH)Source of chirality: l-valinolAbsolute configuration: (S,S)

(S)-4,5-Dihydro-2-(1-((S)-4,5-dihydro-4-isopropyloxazol-2-yl)cyclohexyl)-4-isopropyloxazoleC18H30N2O2[α]D23=-84.2 (c 0.70, MeOH)Source of chirality: l-valinolAbsolute configuration: (S,S)

(S)-4,5-Dihydro-2-(2-((S)-4,5-dihydro-4-isopropyloxazol-2-yl)-1,3-di-o-tolylpropan-2-yl)-4-isopropyloxazoleC29H38N2O2[α]D20=-91.5 (c 0.55, MeOH)Source of chirality: l-valinolAbsolute configuration: (S,S)

(S)-4,5-Dihydro-2-(2-((S)-4,5-dihydro-4-isopropyloxazol-2-yl)-1,3-di-m-tolylpropan-2-yl)-4-isopropyloxazoleC29H38N2O2[α]D20=-100 (c 0.53, MeOH)Source of chirality: l-valinolAbsolute configuration: (S,S)

(S)-4,5-Dihydro-2-(2-((S)-4,5-dihydro-4-isopropyloxazol-2-yl)-1,3-di-p-tolylpropan-2-yl)-4-isopropyloxazoleC29H38N2O2[α]D20=-92.9 (c 0.64, MeOH)Source of chirality: l-valinolAbsolute configuration: (S,S)

(S)-2-(1,3-Bis(4-phenylphenyl)-2-((S)-4,5-dihydro-4-isopropyloxazol-2-yl)propan-2-yl)-4,5-dihydro-4-isopropyloxazoleC39H42N2O2[α]D20=-20.2 (c 0.41, MeOH)Source of chirality: l-valinolAbsolute configuration: (S,S)

(S)-2-(1,3-Bis(4-tert-butylphenyl)-2-((S)-4,5-dihydro-4-isopropyloxazol-2-yl)propan-2-yl)-4,5-dihydro-4-isopropyloxazoleC35H50N2O2[α]D20=-59.5 (c 0.43, MeOH)Source of chirality: l-valinolAbsolute configuration: (S,S)

(S)-4,5-Dihydro-2-(2-((S)-4,5-dihydro-4-isopropyloxazol-2-yl)-1,3-bis(3,5-dimethylphenyl)propan-2-yl)-4-isopropyloxazoleC31H42N2O2[α]D20=-89.4 (c 0.55, MeOH)Source of chirality: l-valinolAbsolute configuration: (S,S)

(S)-2-(1,3-Bis(3,5-di-tert-butylphenyl)-2-((S)-4,5-dihydro-4-isopropyloxazol-2-yl)propan-2-yl)-4,5-dihydro-4-isopropyloxazoleC43H66N2O2[α]D20=-60.9 (c 0.47, MeOH)Source of chirality: l-valinolAbsolute configuration: (S,S)