A molecular modelling explanation of the unexpected stereochemistry observed in the alkylation of oxazinone-derived glycine equivalents using 4-chloromethyl-1, 3, 2-dioxathiolane-2-oxide. Issue 24 (31st December 2015)

• Record Type: Journal Article
• Authors: Jakubowska, Anna; Fijałowski, Łukasz; Nowaczyk, Alicja; Żuchowski, Grzegorz; Kulig, Katarzyna
• Is Part Of: Tetrahedron, asymmetry. Volume 26:Issue 24(2015)
• Page Start: 1408
• Page End: 1415
• Publication Date: 2015-12-31
• Subjects: Asymmetry (Chemistry) -- Periodicals; 547.005
• DOI: 10.1016/j.tetasy.2015.10.021
• Languages: English
• ISSNs: 0957-4166

Abstract

Graphical abstract: Abstract: The ( R )- and ( S )-enantiomers of 4-chloromethyl-1, 3, 2-dioxathiolane-2-oxide were used as 'epoxide-like' synthons in the asymmetric alkylation of the enantiomers of oxazinone-derived glycine equivalents. The configurations of the obtained spiro compounds were easily determined using 2D nuclear Overhauser effect nuclear magnetic resonance experiments. Additionally, the mechanisms of the reactions performed were explained using molecular modelling. The s piro derivatives obtained can also be modified and hydrolysed to their corresponding amino acids, which are derivatives of 1-aminocyclopropane-1-carboxylic acids. Abstract : ( R )-4-Chloromethyl-1, 3, 2-dioxathiolane 2-oxide: C3 H5 ClO3 S [ α ]D 20 = −62.9 ( c 1.470, MeOH), [ α ]D 20 = −43.6 ( c 1.108, CH2 Cl2 ) Source of chirality: chiral substrate Absolute configuration: ( R ) Abstract : ( R )-4-Chloromethyl-1, 3, 2-dioxathiolane 2, 2-dioxide: C3 H5 ClO4 S [ α ]D 20 = −26.4 ( c 1.335, MeOH), [ α ]D 20 = +2.6 ( c 2.965, CH2 Cl2 ) Source of chirality: chiral substrate Absolute configuration: ( R ) Abstract : (1 R, 3 S, 6 S ) - 6- tert -Butyl-1-(chloromethyl)-5-methoxy-6-methyl-7-oxa-4-azaspiro[2.5]oct-4-en-8-one: C13 H20 ClNO3 [ α ]D 20 = +54.8 ( c 2.338, CH2 Cl2 ) Source of chirality: chiral substrate Absolute configuration: (1 R, 3 S, 6 S ) Abstract : (1 S, 3 R, 6 S )-6- tert -Butyl-1-(chloromethyl)-5-methoxy-6-methyl-7-oxa-4-azaspiro[2.5]oct-4-en-8-one: C13 H20 ClNO3 [ α ]D 20 = −19.0 ( c 2.570, CH2 Cl2 ) Source of chirality: chiral substrate Absolute configuration: (1 S, 3 R, 6 S ) Abstract : (1 R, 3 S, 6 R )-6- tert -Butyl-1-(chloromethyl)-5-methoxy-6-methyl-7-oxa-4-azaspiro[2.5]oct-4-en-8-one: C13 H20 ClNO3 [ α ]D 20 = +18.9 ( c 2.530, CH2 Cl2 ) Source of chirality: chiral substrate Absolute configuration: (1 R, 3 S, 6 R ) Abstract : (1 S, 3 R, 6 R )-6- tert -Butyl-1-(chloromethyl)-5-methoxy-6-methyl-7-oxa-4-azaspiro[2.5]oct-4-en-8-one: C13 H20 ClNO3 [ α ]D 20 = −50.1 ( c 2.365, CH2 Cl2 ) Source of chirality: chiral substrate Absolute configuration: (1 S, 3 R, 6 R ) Abstract : (1 S, 3 S, 6 R )-6- tert -Butyl-5-methoxy-6-methyl-1-((4-phenylpiperazin-1-yl)methyl)-7-oxa-4-azaspiro[2.5]oct-4-en-8-one: C23 H33 N3 O3 [ α ]D 20 = −4.2 ( c 1.140, CH2 Cl2 ) Source of chirality: chiral substrate Absolute configuration: (1 S, 3 S, 6 R ) Abstract : C21 H24 N2 O5 : 2-(((1 S, 3 S, 6 R )-6- tert -Butyl-5-methoxy-6-methyl-8-oxo-7-oxa-4-azaspiro[2.5]oct-4-en-1-yl)methyl)isoindoline-1, 3-dione [ α ]D 20 = −24.9 ( c 0.944, CH2 Cl2 ) Source of chirality: chiral substrate Absolute configuration: (1 S, 3 S, 6 R )