Stereoselective Synthesis of an Immunomodulator (+)-Conagenin Using ­Dirhodium(II)-Catalyzed C-H Amination and Chelation-Controlled ­Reductions as Key Steps

Abstract

Stereoselective synthesis of an immunomodulator (+)-conagenin from commercially available optically active methyl 3-hydroxy-2-methylpropanoate was achieved using dirhodium(II)-catalyzed C-H amination and chelation-controlled reductions as key steps.

Key words

conagenin - immunomodulator - dirhodium(II) - C-H amination - chelation control - reduction

References and Notes

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13

All other attempts under several conditions [using various dirhodium(II) catalysts, hypervalent iodine reagents, solvents] gave poorer yields of cyclization product. Development of an alternative route using C-H amination has been investigated and will be reported.

16

Both this result and the fact that no diastereomer was obtained in the condensation of 2 and 3 would reveal that the dirhodium(II)-catalyzed C-H amination of 5 proceeded exclusively with retention of configuration, as Espino and Du Bois have reported. [9]

20

The stereochemistries of neither diastereomer were determined.