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
a   Institut für Chemie und Biochemie, Freie Universität Berlin, Takustr. 3, 14195 Berlin, Germany
,
Timon Kurzawa
a   Institut für Chemie und Biochemie, Freie Universität Berlin, Takustr. 3, 14195 Berlin, Germany
,
Giaime Rancan
a   Institut für Chemie und Biochemie, Freie Universität Berlin, Takustr. 3, 14195 Berlin, Germany
,
Igor Linder
a   Institut für Chemie und Biochemie, Freie Universität Berlin, Takustr. 3, 14195 Berlin, Germany
,
Stefan Leisering
a   Institut für Chemie und Biochemie, Freie Universität Berlin, Takustr. 3, 14195 Berlin, Germany
,
a   Institut für Chemie und Biochemie, Freie Universität Berlin, Takustr. 3, 14195 Berlin, Germany
b   Department of Chemistry, Indian Institute of Engineering Science and Technology, Shibpur, PO-Botanic Garden, Howrah-711 103 (WB), India
,
Max Gart
a   Institut für Chemie und Biochemie, Freie Universität Berlin, Takustr. 3, 14195 Berlin, Germany
,
Reinhold Zimmer
a   Institut für Chemie und Biochemie, Freie Universität Berlin, Takustr. 3, 14195 Berlin, Germany
,
a   Institut für Chemie und Biochemie, Freie Universität Berlin, Takustr. 3, 14195 Berlin, Germany
› Author Affiliations
This work was generously supported by the Deutsche Forschungsgemeinschaft and BayerHealthCare.


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

Supporting Information



Publication History

Received: 10 December 2020

Accepted after revision: 13 January 2021

Article published online:
09 February 2021

© 2021. Thieme. All rights reserved

Georg Thieme Verlag KG
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