The synthesis of C2 symmetry diesters of (3R,4R)-TTFOL through a green and stereoselective (2R,3R)-TADDOL rearrangement

An efficient, green, and atom economic methodology for the stereoselective synthesis of C2 symmetry (3R,4R)-TTFOL diester derivatives has been developed. The procedure occurs through a (2R,3R)-TADDOL dioxolane cleavage and rearrangement under mild conditions by its reaction with a carboxylic acid in the presence of TFAA/H3PO4 without the need for an inert atmosphere to give generally high yields.

Figure optionsDownload as PowerPoint slide

(3R,4R)-2,2,5,5-Tetraphenyltetrahydrofuran-3,4-diacrylateC34H28O5[α]D25 = −75.1 (c 0.010, CHCl3)Source of chirality: asymmetric synthesisAbsolute configuration: (3R,4R)

(3R,4R)-2,2,5,5-Tetraphenyltetrahydrofuran-3,4-dimethacrylateC36H32O5[α]D25 = −114.9 (c 0.009, CHCl3)Source of chirality: asymmetric synthesisAbsolute configuration: (3R,4R)

(3R,4R)-2,2,5,5-Tetraphenyltetrahydrofuran-3,4-diyl-(E)-2-methyl-3-phenylpropenoateC48H40O5[α]D25 = −105.4 (c 0.011, CHCl3)Source of chirality: asymmetric synthesisAbsolute configuration: (3R,4R)

(3R,4R)-2,2,5,5-Tetraphenyltetrahydrofuran-3,4-diyl-(E)-2,3-diphenylpropenoateC58H44O5[α]D25 = −99.5 (c 0.011, CHCl3)Source of chirality: asymmetric synthesisAbsolute configuration: (3R,4R)

(3R,4R)-2,2,5,5-Tetraphenyltetrahydrofuran-3,4-diyl-(E)-3-phenylpropenoateC46H36O5[α]D25 = +38.1 (c 0.010, CHCl3)Source of chirality: asymmetric synthesisAbsolute configuration: (3R,4R)

(3R,4R)-2,2,5,5-Tetraphenyltetrahydrofuran-3,4-diyl-(E)-3-(3,4-diacetoxyphenyl)propenoateC54H44O13[α]D25 = +45.5 (c 0.27, CHCl3)Source of chirality: asymmetric synthesisAbsolute configuration: (3R,4R)

(3R,4R)-2,2,5,5-Tetraphenyltetrahydrofuran-3,4-diyl-(E)-3-(3,4-dimethoxyphenyl)propenoateC50H44O9[α]D25 = +67.3 (c 0.011, CHCl3)Source of chirality: asymmetric synthesisAbsolute configuration: (3R,4R)