Dynamic Kinetic Resolution of Alcohols by Enantioselective Silylation

Simple SummaryContent extracted from patent full text and abstract with AI.

This invention discloses a non-enzymatic dynamic kinetic resolution (DKR) process enabling the enantioselective silylation of chiral alcohols. Using a compatible pair of catalysts — a copper-based enantioselective silylation catalyst and a ruthenium or osmium-based racemization catalyst — the method efficiently transforms racemic (or non-racemic) mixtures of secondary alcohols into enantioenriched silyl ethers, which are valuable intermediates in organic synthesis. The process overcomes the limitations of previous enzymatic methods, allows operation in a single vessel, and has wide substrate scope.

Use CasesContent extracted from patent full text and abstract with AI.

• Synthesis of enantioenriched silyl ether derivatives for pharmaceutical intermediate production.
• Preparation of building blocks for asymmetric organic synthesis in the chemical and fine chemical industries.
• Development of synthetic routes for enantioenriched compounds where silyl protection is required for alcohol functionalities.
• Academic research on asymmetric synthesis and methodology development.

BenefitsContent extracted from patent full text and abstract with AI.

• Enables near-quantitative conversion of racemic chiral alcohols into one enantiomer of silyl ether, surpassing the 50% yield limit of conventional kinetic resolution.
• Non-enzymatic: does not require costly or sensitive enzymes, broadening conditions and scalability.
• High enantioselectivity and functional group tolerance across a diverse set of chiral alcohol substrates (acyclic, cyclic, functionalized, heteroaryl, etc.).
• Orthogonal (parallel) catalysis allows both racemization and silylation in a single-flask process, reducing time, cost, and operational steps.
• Silyl ethers produced can be easily deprotected or used as stable intermediates for further chemical transformations.
• Applicable at room temperature using common solvents, with operational simplicity and reduced risk of side reactions due to catalyst compatibility.

Technical Classifications (CPCs)

Inventors & Applicants

Patent Abstract

The invention relates to non-enzymatic dynamic kinetic resolution (DKR) process for enantioselective silylation of a chiral alcohol, the process comprising reacting a substrate comprising a first enantiomer of the chiral alcohol using a racemization catalyst, and generating from said second enantiomer and a hydrosilane a silyl ether using an enantioselective silylation catalyst, wherein the enantioselective silylation catalyst is a catalytic system comprising a copper salt, an inorganic or organometallic base and (-)-1,2-bis((2R,5R)-2,5-diarylphospholano)ethane or (+)-1,2-bis((2S,5S)-2,5-diarylphospholano)ethane ((R,R)-Ar-BPE or (S,S)-Ar-BPE), and the racemization catalyst is a compound according to Formula I as disclosed herein.