Chiral Copper-BINAM Catalyst for Allylic Amination
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Solution Overview
Problem
Current methods for producing chiral N-substituted allylic amine compounds are inefficient, requiring pre-functionalized substrates and expensive Pd, Rh, or Ir-based catalysts, and are limited in their ability to produce chiral N-aryl allyl amines with poor reaction rates.
Innovation Solution
A method involving the use of copper compounds and chiral ligands for asymmetric allylic amination, where olefins react with substituted hydroxylamines to produce chiral allyl amines through a nitroso-ene reaction, forming a chiral copper-BINAM nitroso complex that coordinates through oxygen, offering high enantioselectivity and yield.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If pre-functionalized substrates and Pd, Rh, or Ir-based catalysts are used for asymmetric allylic amination, then chiral N-substituted allylic amine compounds can be produced, but the production cost increases and reaction efficiency decreases
Solution Approach 1:
The patent changes the catalyst metal parameter from expensive Pd, Rh, or Ir to inexpensive copper, and changes the ligand parameter to chiral diamine ligands. This parameter substitution maintains enantioselectivity while dramatically improving reaction rate and reducing cost, directly resolving the contradiction between reliability and productivity
2Reliability
If pre-functionalized substrates are used for asymmetric allylic amination, then chiral N-substituted allylic amine compounds can be produced, but the number of synthetic steps increases
Solution Approach 1:
The patent extracts and eliminates the unnecessary pre-functionalization step from the synthetic sequence. By using unfunctionalized olefins directly with copper catalysts and chiral diamine ligands, the method achieves high enantioselectivity in a single step, removing the complexity of multiple synthetic operations while maintaining product quality
3Reliability
If expensive Pd, Rh, or Ir-based catalysts are used for asymmetric allylic amination, then chiral N-substituted allylic amine compounds can be produced, but the production cost increases
Solution Approach 1:
The patent replaces expensive, precious metal catalysts (Pd, Rh, Ir) with inexpensive copper catalysts combined with chiral diamine ligands. This substitution dramatically reduces production cost while maintaining high enantioselectivity, making the process economically viable for industrial manufacturing of chiral N-substituted allylic amines
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
This method provides a simple and direct route to chiral allyl amines with high enantioselectivity and yield, suitable for producing commercially useful compounds and bioactive molecules, reducing the need for expensive catalysts and synthetic steps.
Implementation Method 1
A method for producing chiral N-substituted allylic amine compounds is described herein. The method comprises preparation of a chiral N-substituted allylic amine from the corresponding olefins and hydroxylamines, in the presence of a catalyst. The catalyst comprises a copper compound and a chiral ligand.
Implementation Method 2
The catalyst comprises a copper compound and a chiral ligand. The method may be used to produce non-natural chiral ß-aminoacid esters, a sub-class of chiral N-substituted allylic amines.
Data Source
AI summary
The method relates to the field of asymmetric allylic amination and comprises preparing a chiral N-substituted allylic amine compound from the corresponding allylic substrates and substituted hydroxylamines, in the presence of a catalyst, said catalyst comprising copper compounds and a chiral ligand. Examples of chiral amine compounds which can be made using the method include Vigabatrin, Ezetimibe Terbinafine, Naftifine 3-methylmorphine, Sertraline, Cinacalcet, Mefloquine hydrochloride, and Rivastigmine. There are over 20,000 known bioactive molecules with chiral N-substituted allylic amine substructure. The method may also be used to produce non-natural chiral ß-aminoacid esters, a sub-class of chiral N-substituted allylic amine compounds. Examples of ß-aminoacid ester which can be produced by the disclosed method, include, but are not limited to, N-(2-methylpent-1-en-3-yl)benzenamine and Ethyl 2-methylene-3-(phenylamino)butanoate. Further, the products of the method described herein can be used to produce chiral heterocycles and bioactive molecules or materials. A novel chiral copper-BINAM nitrosoarene complex is also set forth.