Verónica Estévez’s research while affiliated with Vrije Universiteit Amsterdam and other places

Supporting Information

We report the use of bifunctional starting materials (ketoacids) in a diastereoselective Passerini three‐center‐two‐component reaction. Study of the reaction scope revealed the required structural features for stereoselectivity in the isocyanide addition. In this system, an interesting isomerization of the primary Passerini product – the α‐carboxamido lactone – into an atypical product, an α‐hydroxy imide, was found to occur under acidic conditions. Furthermore, enantioenriched Passerini products can be generated from an enantioenriched ketoacid obtained by chemoenzymatic synthesis.

A simple and efficient method for the synthesis of highly substituted spiroindoline derivatives is presented. A Fischer indolization is combined with Ugi-type reactions to explore the chemical space concerning this privileged structure. Moreover, spiropiperidine derivatives could be postmodified for the production of a small-molecule library that will be part of the Joint European Compound Library of the European Lead Factory.

A new synthetic approach to 4-aminopyrido[2,3-d]pyrimidines and 4-aminopyrido[3,2-d]pyrimidines based on palladium-catalyzed reaction of isocyanides with readily available N-(bromopyridyl)amidines is reported. The target heterocycles were obtained in generally good to excellent yield. For the two regioisomeric pyrimidopyrimidines, we compared our approach involving oxidative addition with the analogous C–H activation protocol because both methods have been reported for the synthesis of 4-aminoquinazolines. We found that the C–H activation protocol does not allow one to obtain the target pyridopyrimidines, but the imidoylative cross-coupling protocol provided a new entry to the synthesis of these medicinally important scaffolds.