Cyclic sulfates as useful tools in the asymmetric synthesis of 1-aminocyclopropane-1-carboxylic acid derivatives

The enantiomers of 4-(2-methoxyethyl)-1,3,2-dioxathiolane-2,2-dioxide and 4-(methoxymethyl)-1,3,2-dioxathiolane-2,2-dioxide have been used as ‘epoxide-like’ synthons during the asymmetric alkylation of oxazinone-derived glycine equivalents. Using a fully stereoselective synthesis, eight stereoisomers of the spiro derivatives of the glycine equivalents were obtained. The relative configurations of the spiro compounds obtained were easily determined using nuclear magnetic resonance spectroscopy and two dimensional nuclear Overhauser effect experiments. Additionally, one of the spiro derivatives obtained was hydrolyzed to its corresponding amino acid, which was a derivative of 1-aminocyclopropano-1-carboxylic acid, a very important building block that is present in many compounds, which have interesting biological activity.

Figure optionsDownload as PowerPoint slide

(S)-4-Methoxybutane-1,2-diolC5H12O3[α]D20 = −8.4 (c 1.280, CH2Cl2)Source of chirality: chiral substrateAbsolute configuration: (S)

(R)-4-(2-Methoxyethyl)-1,3,2-dioxathiolane-2,2-dioxideC5H10O5S[α]D20 = +15.5 (c 1.310, CH2Cl2)Source of chirality: chiral substrateAbsolute configuration: (R)

(1S,3S,6S)-6-(tert-Butyl)-5-methoxy-1-(2-methoxyethyl)-6-methyl-7-oxa-4-azaspiro[2.5]oct-4-en-8-oneC15H25NO4[α]D20 = +0.6 (c 1.952, CH2Cl2)Source of chirality: chiral substrateAbsolute configuration: (1S,3S,6S)

(1R,3R,6S)-6-tert-Butyl-1-(chloromethyl)-5-methoxy-6-methyl-7-oxa-4-azaspiro[2.5]oct-4-en-8-oneC15H25NO4[α]D20 = +6.6 (c 2.572, CH2Cl2)Source of chirality: chiral substrateAbsolute configuration: (1R,3R,6S)

(1S,3S,6R)-6-(tert-Butyl)-5-methoxy-1-(2-methoxyethyl)-6-methyl-7-oxa-4-azaspiro[2.5]oct-4-en-8-oneC15H25NO4[α]D20 = −6.9 (c 2.474, CH2Cl2)Source of chirality: chiral substrateAbsolute configuration: (1S,3S,6R)

(1R,3R,6R)-6-(tert-Butyl)-5-methoxy-1-(2-methoxyethyl)-6-methyl-7-oxa-4-azaspiro[2.5]oct-4-en-8-oneC15H25NO4[α]D20 = −0.7 (c 2.466, CH2Cl2)Source of chirality: chiral substrateAbsolute configuration: (1R,3R,6R)

(R)-3-Methoxypropane-1,2-diolC4H10O3[α]D20 = −2.2 (c 1.065, CH2Cl2)Source of chirality: chiral substrateAbsolute configuration: (R)

(4S)-4-(Methoxymethyl)-1,3,2-dioxathiolane 2-oxideC4H8O4S[α]D20 = −42.6 (c 1.295, CH2Cl2)Source of chirality: chiral substrateAbsolute configuration: (4S)

(S)-4-(Methoxymethyl)-1,3,2-dioxathiolane-2,2-dioxideC4H8O5S[α]D20 = −7.4 (c 1.365, CH2Cl2)Source of chirality: chiral substrateAbsolute configuration: (S)

(1R,3S,6S)-6-(tert-Butyl)-5-methoxy-1-(methoxymethyl)-6-methyl-7-oxa-4-azaspiro[2.5]oct-4-en-8-oneC14H23NO4[α]D20 = +4.9 (c 2.000, CH2Cl2)Source of chirality: chiral substrateAbsolute configuration: (1R,3S,6S)

(1S,3R,6S)-6-(tert-Butyl)-5-methoxy-1-(methoxymethyl)-6-methyl-7-oxa-4-azaspiro[2.5]oct-4-en-8-oneC14H23NO4[α]D20 = +33.7 (c 1.872, CH2Cl2)Source of chirality: chiral substrateAbsolute configuration: (1S,3R,6S)

(1R,3S,6R)-6-(tert-Butyl)-5-methoxy-1-(methoxymethyl)-6-methyl-7-oxa-4-azaspiro[2.5]oct-4-en-8-oneC14H23NO4[α]D20 = −34.0 (c 1.714, CH2Cl2)Source of chirality: chiral substrateAbsolute configuration: (1R,3S,6R)

(1S,3R,6R)-6-(tert-Butyl)-5-methoxy-1-(methoxymethyl)-6-methyl-7-oxa-4-azaspiro[2.5]oct-4-en-8-oneC14H23NO4[α]D20 = −4.2 (c 2.144, CH2Cl2)Source of chirality: chiral substrateAbsolute configuration: (1S,3R,6R)