Studies on indium-mediated additions to lactones: synthesis of 2-deoxy-2-substituted-3-ulosonic acids

The indium-mediated Reformatsky reaction of a mannose-derived lactone with α,α-disubstituted-α-bromo esters yielded the corresponding ulosonic acid esters as mixtures of anomers. In contrast, the reaction with α-monosubstituted-α-bromo esters is highly stereoselective and afforded a single anomer of the corresponding (2S)-ulosonic acid esters. A mechanistic proposal for the reaction and an explanation of its outcome is discussed. The indium-mediated Reformatsky reaction of the mannose-derived lactone with 2-bromo-lactones was also achieved and the products obtained were consistent with those of our proposed mechanism in all cases. Moreover, indium-mediated allylation of the model sugar lactone was also investigated.

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(2R)-Ethyl 2-deoxy-4,5:7,8-di-O-isopropyliden-2-methyl-α-d-manno-3,6-furanoso-3-octulosonateC17H28O8[α]D25=+1.3 (c 0.9, CHCl3)Source of asymmetry: d-mannoseAbsolute configuration: (2R,3S,4S,5S,6R,7R)

(2R)-Ethyl 2-deoxy-4,5:7,8-di-O-isopropyliden-2-phenyl-α-d-manno-3,6-furanoso-3-octulosonateC17H28O8[α]D25=+23.5 (c 0.4, CHCl3)Source of asymmetry: d-mannoseAbsolute configuration: (2R,3S,4S,5S,6R,7R)

(2R)-Ethyl 2-bromo-2-deoxy-4,5:7,8-di-O-isopropyliden-α-d-manno-3,6-furanoso-3-octulosonateC22H30O8[α]D22=+43.8 (c 0.7, CHCl3)Source of asymmetry: d-mannoseAbsolute configuration: (2R,3R,4S,5S,6R,7R)

(2R)-Ethyl 2-deoxy-4,5:7,8-di-O-isopropyliden-2-propyl-α-d-manno-3,6-furanoso-3-octulosonateC19H32O8[α]D26=-8.5 (c 0.5, chloroform)Source of asymmetry: d-mannoseAbsolute configuration: (2R,3R,4S,5S,6R,7R)

Ethyl 2,2-difluoro-2-deoxy-4,5:7,8-di-O-isopropyliden-α-d-manno-3,6-furanoso-3-octulosonateC16H24F2O8[α]D23=+22.6 (c 1.0, chloroform)Source of asymmetry: d-mannoseAbsolute configuration: (2R,3R,4S,5S,6R,7R)