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.

Tropane-Based Dispirocyclic Oxiranes and Spirocyclic Ketones

“…Pople's small 6-31G* orbital basis set 19 and Dunning's larger aug-cc-pVTZ set 20 were employed throughout this study. Similar to our previous work, 21 utilization of the smaller 6-31G* basis set was necessary to quickly obtain the MP2 energy and gradients during geometry optimization, as well as the MP2 Hessian for further transition-state optimization or frequency calculations. The larger aug-cc-pVTZ basis set was used to obtain more accurate energetic parameters after respective geometry or transition-state optimizations.…”