Towards novel tricyclic motifs: intramolecular C-H arylation as the key step in a formal (3+3) cyclocondensation strategy

Tricyclic scaffolds, structurally related to the well known benzodiazepine drug class, show diverse and strikingly different biological activities than their benzodiazepine counter parts. Interested by this scaffold hopping perspective, we previously developped a continuous flow method converting benzodiazepinediones to oxazoloquinolinones. Exploration of this synthetic route to the corresponding oxazolonaphthyridinone scaffolds met with limited success however, encouraging us to develop a different approach for pyridine based tricyclic motifs. In line with our interest in scaffold hopping, herein we describe a general, convergent (3+3) cyclocondensation approach giving access to [1,3]oxazolo[4,5-c]-1-naphthyridin-4(5H)-ones. The key synthetic steps in this approach are (1) the construction of an amide link connecting two peripheral heterocycles and (2) a palladium-catalysed intramolecular C-H arylation completing the tricyclic derivative.status: publishe

Scaffold Hopping <i>via</i> a Transannular Rearrangement–Encompassing Cascade

A novel reaction cascade for converting benzodiazepinediones into oxazoloquinolinones using carboxylic acid anhydrides in the presence of base has been developed using flow methods. Products are obtained in yields up to 98%

First example of a continuous flow carbonylation reaction using aryl formates as CO precursors

© 2014 Akadémiai Kiadó. The first continuous flow carbonylation reaction using aryl formates as CO precursor is reported. The reaction is practical, scalable and high yielding. The use of a flow protocol safely allows expanding the scope to activated chlorides, nitrogen heterocycles and to the selective introduction of an ester group in dihalo-derivatives. Further selective reduction of the ester formed to an aldehyde in flow is also described.status: publishe