Synthesis, Table of Contents

Synthesis 2022; 54(04): 1091-1100
DOI: 10.1055/s-0040-1706282

special topic

Cycloadditions – Established and Novel Trends – in Celebration of the 70th Anniversary of the Nobel Prize Awarded to Otto Diels and Kurt Alder

Simple Synthesis of Complex Amines from the Diels–Alder Adducts of (–)-Cytisine

Alexey Chuyko

^aLife Chemicals Inc., The Representative Office in Ukraine, 5 Murmanska St., Kyiv 02000, Ukraine

,

Grygoriy Dolgonos

^aLife Chemicals Inc., The Representative Office in Ukraine, 5 Murmanska St., Kyiv 02000, Ukraine

,

Alexander Shivanyuk∗

^aLife Chemicals Inc., The Representative Office in Ukraine, 5 Murmanska St., Kyiv 02000, Ukraine

^bThe Institute of High Technologies, Taras Shevchenko National University of Kyiv, 4 Glushkov St., Kyiv 03187, Ukraine

,

Volodymyr Fetyukhin

^aLife Chemicals Inc., The Representative Office in Ukraine, 5 Murmanska St., Kyiv 02000, Ukraine

,

Oleg Lukin

^aLife Chemicals Inc., The Representative Office in Ukraine, 5 Murmanska St., Kyiv 02000, Ukraine

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Abstract

The Diels–Alder reaction of N-benzylcytisine with N-methyl- and N-benzylmaleimides is 100% endo-selective and gives the corresponding syn- and anti-diastereomers in 11–42% isolated yields. The studies of the reaction progress with LCMS and NMR along with detailed quantum chemical calculations revealed that some Diels–Alder adducts are kinetically and their isomers are thermodynamically controlled products. The Pd/C-catalyzed hydrogenation of benzyl-protected cytisine amine derivatives resulted in the removal of the benzyl group and the addition of hydrogen to the C=C double bond to give the corresponding secondary amines in 45–84% yield. The complete reduction of carbonyl groups in a cytisine derivative with LiAlH₄ in THF under reflux afforded the respective tricyclic triamine. Quantum mechanical calculations for the mechanism of the Diels–Alder reaction between the simplest model compounds are presented.

Key words

Key words

cytisine - maleimides - Diels–Alder reaction - diastereoselectivity - hydrogenation - LiAlH₄ reduction - quantum chemical calculations

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Supplementary Material

Supplementary Material

Supporting Information