N-Acylphthalimides represent an underutilized functional group in organic synthesis. We have found that aldehydes react with N-acylphthalimides to form N,O-acetals. Early optimization efforts suggested that the reaction requires addition of a lithium salt and tertiary amine. More thorough screening of reactions conditions revealed that use of LiBF4, N,N-diisopropylethylamine, and a co-solvent mixture of ethyl acetate and acetonitrile gave higher yields. A further increase in yield (ca. 90%) was observed when powdered 4Å molecular sieves were added to the reaction mixture, which suggests that adventitious water is detrimental to the reaction. A variety of N,O-acetals could be prepared when these conditions were applied to the reaction of N-acetylphthalimide with different aliphatic and highly electrophilic aromatic aldehydes. However, use of methoxy- or hydroxyl-substituted benzaldehydes led to severely reduced yields (ca. &lt;5%). This was overcome by modifying the additives used in the reaction, which further expanded the scope of N,O-acetal products. Alternative acylimides and amides were also probed for their ability to participate under the reaction conditions, which gave rise to N,O-acetals derived from acylimidazoles, acyltriazoles, acylbenzotriazoles, and acyltetrazoles. This presentation will include details related to optimization studies for electron deficient and electron rich aldehydes as well as the scope of amenable aldehydes, acylimides, and acylamides.

Lithium-mediated reaction of N-acylimides with aldehydes: Expanding the scope to include electron-rich aldehydes

251st National Meeting (2016)

The official archive and repository for all ACS Meetings & Expositions abstracts and select posters or presentations.