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Synthesis 2021; 53(02): 309-317
DOI: 10.1055/s-0040-1707313
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Aminocatalytic Synthesis of Uracil Derivatives Bearing a Bicyclo[2.2.2]octane Scaffold via a Doubly Cycloadditive Reaction Cascade

Maciej Saktura
,
Sebastian Frankowski
,
Bartłomiej Joachim
,
Łukasz Albrecht  ∗
This project was realized within the Opus programme (grant number: 2016/23/B/ST5/01927) from the National Science Centre, Poland.
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Dedicated to Professor Grzegorz Mlostoń on the occasion of his 70th birthday

Abstract

Aminocatalytic synthesis of highly enantiomerically enriched uracil derivatives bearing a bicyclo[2.2.2]octane scaffold is described. The developed strategy utilizes 1,3,6-trimethyl-5-formyluracil and α,β-unsaturated aldehydes as starting materials and has been realized employing various aminocatalytic activation strategies operating in a synergistic manner. The reaction cascade can be described as doubly cycloadditive as it consists of two consecutive Diels–Alder cycloadditions allowing for a facile construction of the bicyclo[2.2.2]octane scaffold. Notably, both steps proceed with dearomatization of the partially aromatic uracil moiety. Excellent stereoselectivity of the reaction cascade is ensured by the use of 2-(diphenylmethyl)pyrrolidine as aminocatalyst.

Key words

asymmetric synthesis - organocatalysis - aminocatalysis - uracil - bicyclic compounds - Diels–Alder cycloaddition

Supporting Information

    Supporting information for this article is available online at https://doi.org/10.1055/s-0040-1707313.
  • Supporting Information


Publication History

Received: 06 August 2020

Accepted after revision: 02 September 2020

Article published online:
22 October 2020

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