# Asymmetric Total Syntheses of Eliglustat and C2-epi-Eliglustat

## TL;DR

This paper describes a method to create two drug-like molecules with high precision using a nickel-catalyzed reaction.

## Contribution

A stereocontrolled nickel-catalyzed aldol-like reaction for synthesizing enantiomerically pure compounds.

## Key findings

- A common key step using TMSOTf-mediated aldol-like reaction was developed for both syntheses.
- Dibenzyl acetals significantly influence the stereochemical outcome of the reaction.
- The method allows independent manipulation of amino and hydroxy groups.

## Abstract

Parallel asymmetric total syntheses of eliglustat and
C2-epi-eliglustat are reported. Both approaches feature
a common
key step, which involves a stereocontrolled TMSOTf-mediated aldol-like
reaction of azidoacetyl thioimides with dibenzyl acetals of aromatic
aldehydes catalyzed by chiral nickel­(II) complexes. It is worth noting
that the structure of dibenzyl acetals plays a key role in the stereochemical
outcome of some of these reactions, as supported by theoretical calculations.
Overall, this strategy enables the independent manipulation of the
amino and hydroxy functional groups and favors the isolation of enantiomerically
pure products.