# Skeletal Transformations Observed in the Reaction of a Tricyclic Thymine Nucleoside with Dicarbonyl Compounds

## TL;DR

A tricyclic thymine nucleoside reacts with dicarbonyl compounds to form new complex ring systems and bonds efficiently.

## Contribution

A new synthetic method for creating polycyclic nucleosides via enamine–iminium mechanisms without catalysts.

## Key findings

- Unusual ring systems and stereogenic centers are formed in a single step from the reaction.
- The reaction proceeds through a nucleophilic attack and enamine–iminium mechanism.
- The method allows for further chemical modifications to create highly functionalized nucleosides.

## Abstract

Some intriguing skeletal transformations were observed
in the reaction
of α-hydroxypyrrolidine thymine nucleoside 2 with
different dicarbonyl compounds. In these reactions, unusual ring systems,
together with new C–C bonds and stereogenic centers of defined
configuration, were formed in a single step. These reactions were
initiated by the nucleophilic attack of the NH of the pyrrolidine
ring, present on 2, on one of the carbonyl moieties of
a dicarbonyl reagent and seem to proceed through an enamine–iminium
mechanism. The present methodology is particularly attractive because
no catalyst or aggressive conditions are needed. The new polycyclic
nucleosides obtained from 2 can be good scaffolds for
diversification. In fact, modification and derivatization can be achieved
by performing further chemical transformations of the functional groups
present in some of them. This may lead to the formation of new highly
functionalized nucleosides. Our results show the high synthetic potential
of 2 to construct complex systems in an efficient way.
On the other hand, the enamine chemistry involved in the particular
reactivity of the α-hydroxy pyrrolidine ring present in 2 has no connection with the nucleobase and could be extended
to simple glycosides preserving this essential ring system.