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

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

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

Publication History

Received: 13 April 2021

Accepted after revision: 02 July 2021

Article published online:
16 August 2021

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