Reaction via Pyridinium-type Salt Intermediate: Chemoselective Deprotection of Acetals in the Presence of Ketals and Nucleophilic Substitution

Although acetals are useful protective groups for carbonyl functions and widely used in organic synthesis, their protection and deprotection under acidic conditions unable to use the substrates with acid labile functions. We recently found that the combination of TESOTf (Et3SiOTf)—2,6-lutidine or 2,4,6-collidine was effective for the deprotection of acetal. The reaction proceeded under nearly neutral conditions and was applicable to the substrates with acid labile functions, and the most noteworthy of this method is the achievement of the chemoselective deprotection of acetals in the presence of ketals. The above reaction proceeds via pyridinium-type salt intermediates, which are found to be highly reactive toward various nucleophiles not only H2O but also heteroatom and carbon nucleophiles affording the corresponding substituted products. This reaction could be conducted under mild reaction conditions whereas conventional methods need harsh reaction conditions. This methodology is also applicable to the deprotection of acetal-type protective groups such as MOM-type ethers, THP ether, and methylene acetal, and the combination of TMSOTf (TESOTf)—2,2’-bipyridyl afforded the best result.