UNIST Develops Safe and Simple Synthesis Method for Key Drug Development Compound 'Allen'

Combining Three Components... Simplifying Complex Chemical Reactions

Revealing the Principles of Synthesis Through Intermediate Analysis

A new technology has been developed for safely and efficiently synthesizing compounds essential for drug development.

A joint research team led by Professor Hong Sungyu and Professor Jan-Uwe Rohde from the Department of Chemistry at UNIST (President Park Jongrae) has discovered a method for synthesizing allenes with various components without using highly reactive and hazardous chemicals.

Research team (from left: Professor Hong Seongyu, Ji Hwan Jeon, Researcher Kim Geonha, Professor Jan-Uwe Rohde).

Allenes are compounds in which carbon atoms are doubly bonded in a unique manner, playing a crucial role in drug discovery and synthetic chemistry.

This synthesis method uses more stable organic halides instead of unstable organometallic compounds. Organic halides are substances in which halogen elements such as bromine or iodine are attached to organic compounds, allowing for safer reactions compared to conventional methods.

The research team sequentially combined three compounds?1,3-enyne, alkyl iodide, and aryl iodide?under nickel-catalyzed and reductive conditions to synthesize allenes with a uniform structure. As a result, only compounds with the same structure were produced, without forming irregular structures.

This process demonstrates high chemoselectivity and regioselectivity, enabling the efficient synthesis of complex allenes. Chemoselectivity refers to the selective occurrence of the desired chemical reaction, while regioselectivity means controlling the reaction to occur at a specific position within the molecule.

Multi-component reactions that combine more than three compounds at once are known as useful synthetic pathways. The research team expanded this reaction to more complex structures and confirmed broad functional group tolerance by using various types of allenes. This proved that the method can stably react with substances possessing diverse chemical properties.

First authors Kim Geonha and Jeon Jihwan explained, "We found that the reduced nickel complex plays a key role in the main step of this reaction," adding, "We directly identified and studied the unstable and highly reactive low-valent nickel organometallic complexes."

Professor Hong Sungyu stated, "We can now synthesize complex allenes using a safe and simple method," adding, "This opens new possibilities in the field of synthetic chemistry."

Professor Jan-Uwe Rohde added, "Understanding the reactivity of such catalysts will also help in developing coupling reactions that connect two compounds to create new ones."

Synthesis and Spectroscopic Analysis of Nickel Complexes Used as Catalysts.

The research results were published online on May 28 in the internationally renowned journal ACS Catalysis.

The study was supported by the Leading Research Center (ERC) project and the Mid-career Researcher Program of the National Research Foundation of Korea.