One-Pot Diastereoselective Synthesis of Pyrrolopiperazine-2,6-diones by a Ugi/Nucleophilic Substitution/N-Acylation Sequence.

The diastereoselective synthesis of two families of pyrrolopiperazine-2,6-diones is presented. These compounds were prepared by one-pot Ugi/nucleophilic substitution/N-acylation/debenzoylation/(elimination) sequences. This novel route provides straightforward access to a wide variety of pyrrolopiperazine-2,6-diones with high chemical yields and complete diastereoselectivities. The proposed synthetic strategy poses a significant improvement compared to the syntheses of pyrrolopiperazine-2,6-diones previously described, as it allows introduction of different substituents to the C4 position and the diastereoselective generation of a new stereogenic center on the bridgehead carbon (C8a).

Keto-Enol Tautomerism in Passerini and Ugi Adducts.

The use of arylglyoxal as starting material in Passerini and Ugi reactions affords ß-ketoamides. This has allowed to study keto-enol tautomerism in these systems and assess the way in which the presence of acyloxy or aminoacyl groups bound to the C2 position affects such tautomerism, and to investigate the reactivity of both the enol and carbonyl forms. In this work we also prove the versatility of the Passerini reaction, since depending on the conditions to which the corresponding adducts are subjected different products of synthetic interest can be obtained.

One-Pot Synthesis of Enantiopure Pyrrolopiperazines.

A simple one-pot protocol for the synthesis of fused pyrrolopiperazines with a complete diastereoselectivity has been developed. This novel methodology combined the Ugi reaction with a spontaneous enamine alkylation on a multicomponent domino reaction, starting from nonprotected diamines and arylglyoxals.