Stereoselective synthesis of polysubstituted 2-carboxy tetrahydrofurans from trichloromethyl carbinols
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Abstract
Polysubstituted tetrahydrofurans, primarily as components of deoxy-C-furanosides, contribute to the biological activities of many antiviral and antibacterial compounds. Several methods are available for the preparation of specific polysubstituted tetrahydrofuran stereoisomers, but few methods offer comparable access to any desired single stereoisomer or a complete library of stereoisomers in a limited number of steps. Our approach enables the predictable and high yielding installation of each chiral center along the novel synthetic pathway. Beginning with either (R)- or (S)-Wynberg lactone, various trisubstituted tetrahydrofuran-2-carboxylic acids can be prepared in five steps without employment of protecting groups. Using this approach, we created twenty trisubstituted tetrhydrofuran-2-carboxylic acids, including a library of eight stereoisomers. This work emphasizes the ability to control the configuration of each chiral center during the synthesis and highlights the ease with which trisubstituted tetrahydrofurans bearing different substituents at C5 can be prepared.