Access to Highly Substituted Pyrimidine N-Oxides and 4-Acetoxymethyl-Substituted Pyrimidines via the LANCA Three-Component Reaction–Cyclocondensation Sequence

Dedicated to Professor Heinz Heimgartner on the occasion of his 80^th birthday

Abstract

The LANCA three-component reaction of lithiated alkoxy­allenes (LA), nitriles (N), and carboxylic acids (CA) smoothly provides β-alkoxy-β-ketoenamides in broad structural variety. The subsequent cyclocondensation of these compounds with hydroxylamine hydrochloride afforded a large library of pyrimidine N-oxides under mild conditions and in good yields. Their synthetic utility was further increased by the Boekelheide rearrangement leading to 4-acetoxymethyl-substituted pyrimidines. With trifluoroacetic anhydride the rearrangement proceeds even at room temperature and directly furnishes 4-hydroxymethyl-substituted pyrimidine derivatives. The key reactions are very robust and work well even in the presence of sterically demanding substituents.

Key words

alkoxyallene - β-alkoxy-β-ketoenamide - pyrimidine N-oxide - Boekelheide rearrangement - oxidation

Publication History

Received: 10 December 2020

Accepted after revision: 13 January 2021

Article published online:
09 February 2021

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