Chemoselective Nucleophilic Functionalizations of Aromatic Aldehydes and Acetals via Pyridinium Salt Intermediates

Abstract

The development of a novel chemoselective functionalization can diversify the strategy for synthesizing the target molecules. The perfect chemoselectivity between aromatic and aliphatic aldehydes is difficult to achieve by the previous methods. The aromatic aldehyde-selective nucleophilic addition in the presence of aliphatic aldehydes was newly accomplished. Namely, the aromatic aldehyde-selective nucleophilic addition using arenes and allyl silanes proceeded in the presence of trialkylsilyl triflate and 2,2′-bipyridyl, while the aliphatic aldehydes completely remained unchanged. The reactive pyridinium-type salt intermediate derived from an aromatic aldehyde chemoselectively underwent the nucleophilic substitution. Moreover, the aromatic acetals as the protected aldehydes could be directly transformed into similar pyridinium salt intermediates, which reacted with various nucleophiles coexisting with the aliphatic aldehydes.

Theoretical Analysis of Selectivity Differences in Ketoreductases toward Aldehyde and Ketone Carbonyl Groups

“…The expression and purification steps of Lk ADH and Ch KRED12 are analogous to those reported in the literature, , and detailed steps are given in the Supporting Information. Substrates 3-acetylbenzaldehyde and 4-acetyl-[1,1-biphenyl]-4-formaldehyde were synthesized according to the methods reported in the literature. , 4-Acetylbenzaldehyde was purchased from Aladdin Chemicals Co. Ltd. (Shanghai, China). All chemicals and reagents were used without further purification.…”

“…Substrates 3-acetylbenzaldehyde and 4-acetyl-[1,1-biphenyl]-4-formaldehyde were synthesized according to the methods reported in the literature. 18,19 4-Acetylbenzaldehyde was purchased from Aladdin Chemicals Co. Ltd. (Shanghai, China). All chemicals and reagents were used without further purification.…”