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

Luise Schefzig; Timon Kurzawa; Giaime Rancan; Igor Linder; Stefan Leisering; Mrinal K. Bera; Max Gart; Reinhold Zimmer; Hans-Ulrich Reissig

doi:10.1055/s-0040-1706020

Synthesis, Table of Contents

Synthesis 2021; 53(12): 2067-2080
DOI: 10.1055/s-0040-1706020

paper

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

Luise Schefzig

^aInstitut für Chemie und Biochemie, Freie Universität Berlin, Takustr. 3, 14195 Berlin, Germany

,

Timon Kurzawa

^aInstitut für Chemie und Biochemie, Freie Universität Berlin, Takustr. 3, 14195 Berlin, Germany

,

Giaime Rancan

^aInstitut für Chemie und Biochemie, Freie Universität Berlin, Takustr. 3, 14195 Berlin, Germany

,

Igor Linder

^aInstitut für Chemie und Biochemie, Freie Universität Berlin, Takustr. 3, 14195 Berlin, Germany

,

Stefan Leisering

^aInstitut für Chemie und Biochemie, Freie Universität Berlin, Takustr. 3, 14195 Berlin, Germany

,

Mrinal K. Bera

^aInstitut für Chemie und Biochemie, Freie Universität Berlin, Takustr. 3, 14195 Berlin, Germany

^bDepartment of Chemistry, Indian Institute of Engineering Science and Technology, Shibpur, PO-Botanic Garden, Howrah-711 103 (WB), India

,

Max Gart

^aInstitut für Chemie und Biochemie, Freie Universität Berlin, Takustr. 3, 14195 Berlin, Germany

,

Reinhold Zimmer∗

^aInstitut für Chemie und Biochemie, Freie Universität Berlin, Takustr. 3, 14195 Berlin, Germany

,

Hans-Ulrich Reissig ∗

^aInstitut für Chemie und Biochemie, Freie Universität Berlin, Takustr. 3, 14195 Berlin, Germany

› Author Affiliations

Abstract

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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

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References

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