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

Abstract

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 α-enaminones in good yields. Deuteration of the cyclopentene scaffold can also be performed using D₂O as a source of D₂. A sequential process for the synthesis of α-enaminones directly from furfural is also described. The methodology allows the preparation of a previously reported ATP-sensitive potassium channel agonist in 71% yield.