Chelation-Assisted Regioselective C−O Bond Cleavage Reactions of Acetals by Grignard Reagents. A General Procedure for the Regioselective Synthesis of Protected Polyols Having One Free Hydroxy Group

• Published in: Journal of organic chemistry 1999-01, Vol.64 (2), p.532-539
• Main Authors: Cheng, Wen-Lung, Shaw, Yeng-Jeng, Yeh, Sue-Min, Kanakamma, Puthuparampil P, Chen, Yu-Huey, Chen, Chuo, Shieu, Jia-Cheng, Yiin, Shaang-Jyh, Lee, Gene-Hsiang, Wang, Yu, Luh, Tien-Yau
• Format: Article
• Language: English
• ISSN: 0022-3263; 1520-6904
• DOI: 10.1021/jo981579a

Acetals containing a neighboring heteroatom react with the Grignard reagent in aromatic hydrocarbon solvents regioselectively. The auxiliary moiety can be hydroxy, alkoxy, or amino but not sulfur. Chelation plays a key role in directing the regioselectivity of this ring opening reaction. The reactions of acetonide derivatives of monosaccharides under these conditions afford the corresponding products having only one free hydroxy group at the specific position. Fully protected mannosamine derivative is prepared in good yield. The stereochemistry of the carbon center where auxiliary group is attached can be either syn or anti to the acetal oxygen moiety where cleavage of the C−O bond occurs. However, difference in reactivity has been found in the reaction of tris-acetonide of sorbitol with MeMgI. Regioselective ring opening of the acetal group at the anomeric carbon generates a hemiacetal which underwent further nucleophilic addition to furnish the corresponding alcohol stereoselectively.