Related Experiment Video
Updated: Jun 13, 2026

Efficient Construction of Drug-like Bispirocyclic Scaffolds Via Organocatalytic Cycloadditions of α-Imino γ-Lactones and Alkylidene Pyrazolones
Published on: February 7, 2019
Enantioselective chemoenzymatic synthesis of cis- and trans-2,5-disubstituted morpholines
Bas Ritzen1, Steven Hoekman, Elena Durán Verdasco
1Radboud University Nijmegen, Institute for Molecules and Materials, Heyendaalseweg 135, NL-6525 AJ Nijmegen, The Netherlands.
Abstract:
A versatile synthesis of enantiomerically pure cis- and trans-2,5-disubstituted morpholines is described. Hydroxynitrile lyase-mediated cyanide addition onto aldehydes provided cyanohydrins in virtually quantitative yield and excellent enantioselectivity. Subsequent formation of diastereomerically pure amino esters via a three-step, one-pot reduction-transimination-reduction sequence followed by reduction and simultaneous protection provided cyclization precursors. Finally, cyclization and SmI(2)-mediated reductive detosylation completed the synthesis of cis- and trans-2,5-disubstituted morpholines in good yields and excellent diastereoselectivities.
Related Concept Videos
Prochirality
Synthesis of α-Substituted Carbonyl Compounds: The Stork Enamine Reaction
Diels–Alder Reaction Forming Bridged Bicyclic Products: Stereochemistry
SN2 Reaction: Stereochemistry
If the substrate is an achiral molecule at the α-carbon, the inversion of configuration is not observed.
ortho–para-Directing Activators: –CH3, –OH, –⁠NH2, –OCH3
Preparation of 1° Amines: Hofmann and Curtius Rearrangement Overview

![Solid-phase Synthesis of [4.4] Spirocyclic Oximes](/_next/image?url=https%3A%2F%2Fcloudfront.jove.com%2FCDNSource%2Fteasers%2F58508.jpg&w=3840&q=50)