Upgrading furanic platforms to α-enaminones: tunable continuous flow hydrogenation of bio-based cyclopentenones

Here we describe a tunable continuous flow hydrogenation of trans-4,5-diamino cyclopentenones (DCPs) allowing the selective stepwise synthesis of novel bifunctionalized cyclopentanones (up to 96% yield and >92% selectivity). Stability studies of the diamino cyclopentanone motif led to the development of an elimination procedure yielding the corresponding alpha-enaminones in good yields. Deuteration of the cyclopentene scaffold can also be performed using D2O as a source of D-2. A sequential process for the synthesis of alpha-enaminones directly from furfural is also described. The methodology allows the preparation of a previously reported ATP-sensitive potassium channel agonist in 71% yield.

Automated summary

In this study, a tunable continuous flow hydrogenation method was used to selectively and stepwise synthesize novel bifunctionalized cyclopentanones with high yields and selectivity. The stability studies of the diamino cyclopentanone motif also led to the development of an elimination procedure for the synthesis of corresponding alpha-enaminones. Deuteration of the cyclopentene scaffold and the sequential synthesis of alpha-enaminones directly from furfural were also demonstrated. The methodology presented in this study is of great significance for the synthesis of ATP-sensitive potassium channel agonists.