Chemo- and Diastereoselective Entries into All-Carbon & alpha;-Quaternary Aldehydes via C-C Insertion of 4-Diazoisoquinolin-3-ones into C-CHO Bonds

Herein,we describe a chemo- and diastereoselective formal C-Cinsertion reaction of 1,2-disubstituted 4-diazo-3(2H)-isoquinolones and 4-diazoisochroman-3-one into C-CHO bondsof aldehydes, delivering all-carbon & alpha;-quaternary aldehydes bearingmedicinally important 1,4-dihydro-3(2H)-isoquinolonescaffold. Our protocol is enabled by the preferential 1,2-carbon migrationover more common 1,2-H shift. The corresponding reactiontolerates a wide range of functionalities in both aldehyde and diazocomponents, giving the target homologated aldehydes in generally highyields. The synthetic utility of this method has been further showcasedby some transformations of the formyl moiety.

Automated summary

Here, a chemo- and diastereoselective formal C-C insertion reaction was described, which introduced 1,2-disubstituted 4-diazo-3(2H)-isoquinolones and 4-diazoisochroman-3-one into the C-CHO bonds of aldehydes, resulting in all-carbon α-quaternary aldehydes bearing medicinally important 1,4-dihydro-3(2H)-isoquinolone scaffold. The protocol exhibited preferential 1,2-carbon migration over the common 1,2-H shift, and the reaction tolerated various functionalities in both aldehyde and diazo components, providing the target homologated aldehydes in generally high yields. The synthetic utility of this method was further demonstrated by transformations of the formyl moiety.