Optically Active Cyclic Amine Synthesis via Transition Metal Catalysis
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Solution Overview
Problem
Existing processes for preparing optically active amines are often unsatisfactory for structurally different substrates, with issues in chemical yield, enantiomeric excess, selectivity, purity, reaction time, and availability of starting materials and auxiliaries.
Innovation Solution
A process for preparing optically active cyclic amines using a catalytically active optically active complex of transition metals, such as ruthenium, rhodium, or iridium, with organic ligands, to convert racemic imines into optically active compounds with high enantioselectivity, achieving cis configuration on chiral centers.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Manufacturing precision
If classical optical resolution via diastereomeric salts or enantioselective reactions with optically active starting materials is used, then optically active amines can be prepared, but the processes are limited to specific substrates and give unsatisfactory results in chemical yield, enantiomeric excess, and selectivity for structurally different substrates
Solution Approach 1:
The patent employs transition metal catalysts with variable oxidation states and different ligand environments to achieve enantioselective transformation across diverse substrates. By changing catalyst parameters (metal center, ligand type, stoichiometry) rather than developing entirely different reaction pathways for each substrate type, the process maintains high enantiomeric excess while expanding substrate scope
Solution Approach 2:
The transition metal complex acts as an intermediary that facilitates enantioselective transformation without being consumed. The metal catalyst mediates the reaction between racemic or achiral starting materials and chiral products, enabling broad substrate applicability while maintaining manufacturing precision through its chiral ligand environment
2Manufacturing precision
If enzymatic reactions or synthetic optically active reagents are used, then enantioselective conversion can be achieved, but reaction time increases and availability of starting materials and auxiliaries becomes problematic
Solution Approach 1:
The patent replaces enzymatic mechanisms with transition metal-catalyzed mechanisms. Instead of relying on biological enzymes with complex active sites and substrate specificities, the invention uses well-defined metal complexes with tunable electronic and steric properties, achieving comparable selectivity with faster reaction kinetics and broader substrate tolerance
3Quantity of substance
If known processes for preparing optically active amines are applied to structurally different substrates, then some substrates can be converted, but chemical yield, purity, and reaction time become unsatisfactory
Solution Approach 1:
The transition metal catalyst system exhibits universal applicability across different substrate classes (cyclic imines, acyclic imines, various functional groups). A single catalytic platform with adjustable ligands can handle diverse substrates, ensuring consistent chemical yield and purity without requiring substrate-specific optimization, thereby improving process reliability
Applied Scientific Principles
This section explains which scientific principles are used to turn an abstract innovation direction into a practical engineering solution.
Function Achieved in This Case
The process achieves high selectivity and enantiomeric excess, with cis compounds obtained with selectivity of 60-100% and enantioselectivity of 20-100%, providing a reliable method for producing optically active amines suitable as intermediates for active ingredients.
Implementation Method 1
converting an imine of the formula (II) or a salt thereof in the presence of hydrogen or a hydrogen donor and a nonenzymatic catalyst which comprises a catalytically active optically active complex of one or more transition metals from the group of ruthenium, rhodium, palladium, iridium, osmium, platinum, iron, nickel and samarium, preferably one or more transition metals from the group of ruthenium, rhodium, palladium and iridium, especially ruthenium and iridium, with organic ligands
Implementation Method 2
converting an imine of the formula (II) or a salt thereof in the presence of hydrogen or a hydrogen donor and a nonenzymatic catalyst
Data Source
AI summary
Optically active cyclic amines of the formula (I) or salts thereofin which A, R0, R are each as defined in claim 1, and R0 and A, or R and A, or R0 and R may also form rings,where R and the NH—R0 group on the two ring carbon atoms marked with an asterisk (*) in each case are arranged in cis arrangement to one another and the stereochemical configuration on these carbon atoms is different from the racemic configuration, can be prepared effectively by a process, which comprises converting an imine (a racemic imine) of the formula (II)in which A, R0 and R are each as defined in formula (I),in the presence of hydrogen or a hydrogen donor and a nonenzymatic catalyst which comprises a catalytically active optically active complex of one or more transition metals from the group of ruthenium, rhodium, palladium, iridium, osmium, platinum, iron, nickel and samarium with organic ligands, to the compound of the formula (I).