Methodology for in Situ Protection of Aldehydes and Ketones Using Trimethylsilyl Trifluoromethanesulfonate and Phosphines

A methodology for selective transformations of ketones, esters, Weinreb amides, and nitriles in the presence of aldehydes has been developed. The use of a combination of PPh3-trimethylsilyl trifluoromethanesulfonate (TMSOTf) promotes selective transformation of aldehydes to their corresponding, temporarily protected, O,P-acetal type phosphonium salts. Because, hydrolytic work-up following ensuing reactions of other carbonyl moieties in the substrates liberates the aldehyde moiety, a sequence involving aldehyde protection, transformation of other carbonyl groups, and deprotection can be accomplished in a one-pot manner. Furthermore, the use of PEt3 instead of PPh3 enables ketones to be converted in situ to their corresponding O,P-ketal type phosphonium salts and, consequently, selective transformations of esters, Weinreb amides, and nitriles in the presence of ketones can be performed. This methodology is applicable to various dicarbonyl compounds, including substrates that possess heteroaromatic skeletons and hydroxyl protecting groups.