SnCl4 Promoted Efficient Cleavage of Acetal/Ketal Groups with the Assistance of Water in CH2Cl2

Abstract

Acetalization and deacetalation are a pair of routine manipulations to protect and deprotect the 4- and 6-hydroxyl groups of glycosides in the synthesis of glycosyl building blocks. In this study, we found that treatment of SnCl4 with various carbohydrates containing acetal/ketal groups with the assistance of water in CH2Cl2 led to deacetalization/deketalization products in almost quantitative yields. In addition, for substrates containing both acetal/ketal and p-methoxylbenzyl groups, we also found that the p-methoxylbenzyl group was selectively cleaved by the use of a catalytic amount of SnCl4, while the acetal/ketal groups remained. Furthermore, based on this, 4,6-benzylidene glycosides can be conveniently converted to 4,6-OAc or 4-OH, 6-OAc glycosides.

Lewis Acid Promoted Deprotection of Benzylidene Acetals and p-Methoxybenzyl Ethers with Mercaptoacid Acid as Scavenger

“…Due to the electron donating nature of the methoxy group its benzylic cation is stabilized compared to unfunctionalized benzyl ether, which makes the PMB ether more labile under oxidative conditions with 2,3-dichloro-5,6-dicyano- p -benzoquinone (DDQ) or ceric ammonium nitrate (CAN) . Alternatively the PMB ether can be cleaved under acidic conditions with Lewis/Brønsted acids, such as TFA, , HF-pyridine, FeCl 3 , SnCl 4 , and HCl/hexafluoroisopropanol …”

“…Due to the electron donating nature of the methoxy group its benzylic cation is stabilized compared to unfunctionalized benzyl ether, which makes the PMB ether more labile under oxidative conditions with 2,3-dichloro-5,6dicyano-p-benzoquinone (DDQ) or ceric ammonium nitrate (CAN). 16 Alternatively the PMB ether can be cleaved under acidic conditions with Lewis/Brønsted acids, such as TFA, 17,18 HF-pyridine, 19 FeCl 3 , 20 SnCl 4 , 21 and HCl/hexafluoroisopropanol. 22 The PMB ether can be introduced directly by treatment of the alcohol by base and p-methoxybenzyl chloride or come from the analogous but more stable p-chlorobenzyl ether by palladium catalysis chemistry.…”