Synthesis of Pyrrolo[2,3-d]pyrimidines by Copper-Mediated Carbomagnesiations of N-Sulfonyl Ynamides and Application to the Preparation of Rigidin A and a 7-Azaserotonin Derivative.

Abstract

The treatment of readily available N-alkynyl-5-iodo-6-sulfamido-pyrimidines with iPrMgCl⋅LiCl followed by a transmetalation with CuCN⋅2 LiCl produces, after intramolecular carbocupration, metalated pyrrolo[2,3-d]pyrimidines. Quenching of these pyrimidines with allylic halides or acid chlorides results in polyfunctional pyrrolo[2,3-d]pyrimidines. Further reaction with ICl and a Negishi cross-coupling, using PEPPSI-iPr as the catalyst, furnishes fully substituted N-heterocycles. A formal synthesis of the marine alkaloid rigidin A has been achieved as well as the preparation of a derivative of 7-azaserotonine, related to the natural hormone serotonin.