• HOME
  • NEWS
  • EXPLORE
    • CAREER
      • Companies
      • Jobs
    • EVENTS
    • iGEM
      • News
      • Team
    • PHOTOS
    • VIDEO
    • WIKI
  • BLOG
  • COMMUNITY
    • FACEBOOK
    • INSTAGRAM
    • TWITTER
Thursday, August 7, 2025
BIOENGINEER.ORG
No Result
View All Result
  • Login
  • HOME
  • NEWS
  • EXPLORE
    • CAREER
      • Companies
      • Jobs
        • Lecturer
        • PhD Studentship
        • Postdoc
        • Research Assistant
    • EVENTS
    • iGEM
      • News
      • Team
    • PHOTOS
    • VIDEO
    • WIKI
  • BLOG
  • COMMUNITY
    • FACEBOOK
    • INSTAGRAM
    • TWITTER
  • HOME
  • NEWS
  • EXPLORE
    • CAREER
      • Companies
      • Jobs
        • Lecturer
        • PhD Studentship
        • Postdoc
        • Research Assistant
    • EVENTS
    • iGEM
      • News
      • Team
    • PHOTOS
    • VIDEO
    • WIKI
  • BLOG
  • COMMUNITY
    • FACEBOOK
    • INSTAGRAM
    • TWITTER
No Result
View All Result
Bioengineer.org
No Result
View All Result
Home NEWS Science News Health

One-step synthesis of pharmaceutical building blocks: new method for anti-Michael reaction

by
July 11, 2024
in Health
Reading Time: 4 mins read
0
Share on FacebookShare on TwitterShare on LinkedinShare on RedditShare on Telegram

In 1887, chemist Sir Arthur Michael reported a nucleophilic addition reaction to the β-position of α,β– unsaturated carbonyl compounds. These reactions, named Michael addition reactions, have been extensively studied to date. In contrast, the anti-Michael addition reaction, referring to the nucleophilic addition reaction to the α-position, has been difficult to achieve. This is due to the higher electrophilicity of the β-position compared to the α-position. Previous attempts to overcome these difficulties have involved two main methods. The first is restricting the addition position via intramolecular reactions, while the second method involves introducing a strong-electron withdrawing group at the β-position. However, these methods are not ideal for synthesizing complex molecules via the anti-Michael reaction.

Conventional Michael addition reaction (top) and the anti-Michael addition reaction developed in this study (bottom)

Credit: Cannot be reused without permission

In 1887, chemist Sir Arthur Michael reported a nucleophilic addition reaction to the β-position of α,β– unsaturated carbonyl compounds. These reactions, named Michael addition reactions, have been extensively studied to date. In contrast, the anti-Michael addition reaction, referring to the nucleophilic addition reaction to the α-position, has been difficult to achieve. This is due to the higher electrophilicity of the β-position compared to the α-position. Previous attempts to overcome these difficulties have involved two main methods. The first is restricting the addition position via intramolecular reactions, while the second method involves introducing a strong-electron withdrawing group at the β-position. However, these methods are not ideal for synthesizing complex molecules via the anti-Michael reaction.

In a new study, a global team of researchers, led by Professor Takanori Matsuda and including Mr. Ryota Moro, both from the Department of Applied Chemistry at Tokyo University of Science, Japan, as well as including Assistant Professor Hirotsugu Suzuki from the Tenure-Track Program for Innovative Research at the University of Fukui, Japan, successfully achieved palladium-catalyzed anti-Michael addition reaction of acrylamides. This represents the first example of an anti-Michael-type addition reaction. “We found that the presence of a catalytic amount of palladium(II) trifluoroacetate Pd(TFA)2 is capable of facilitating the anti-Michael addition of indole to acrylamide with an aminoquinoline group as a directing group, producing the addition product in high-yield,” explains Prof. Matsuda.

Their study was made available online on May 14, 2024, and published in Volume 146, Issue 20 of the Journal of the American Chemical Society on May 22, 2024.

The team reasoned introducing a directing group into an α,β-unsaturated carbonyl compound could facilitate an anti-Michael type addition reaction by stabilizing the reaction intermediate. To test this, the researchers first used an acrylamide having an aminoquinoline-directing group, and a nucleophile, 1-methylindole, as model substrates to investigate the anti-Michael type addition reaction in the presence of the palladium catalyst. This reaction produced the desired product with a 90% yield. At a reaction scale of two millimoles, there was no yield loss, signifying the practicality of the reaction.

This reaction was also carried out with β-substituted cinnamamide derivatives and crotonamide derivatives with an alkyl group. Moreover, the reaction proceeded smoothly with a wide range of nucleophiles, including many indoles, heterocyclic compounds such as pyrroles and thiophenes, and electron-rich aromatic compounds. Additionally, the aminoquinoline-directing group used in this reaction can be converted to carboxylic acids and other amides, signifying the usefulness of the reaction.

The researchers also investigated the mechanism for this reaction through labeling experiments. They found that initially, the acrylamide coordinates to Pd(TFA)2 to form a five-membered ring palladacyle intermediate. The reaction then proceeds with the nucleophilic attack by indole on the intermediate, producing alkylpalladium species. Finally, an acid removes palladium and regenerates Pd(TFA)2, producing the desired α-substituted carbonyl compound.

Highlighting the potential applications of this study, Dr. Suzuki says, “The anti-Michael type addition is expected to become an ideal one-step reaction with 100% atomic efficiency for the synthesis of α-substituted carbonyl compounds, which are often used in pharmaceuticals. Our method will enable the widespread application of this reaction.”

Overall, this novel method can lead to efficient and sustainable synthesis of α-substituted carbonyl compounds and consequently pharmaceuticals, among other organic compounds.

 

***

 

Reference

DOI: https://doi.org/10.1021/jacs.4c00841

Authors: Hirotsugu Suzuki1, Ryota Moro2, and Takanori Matsuda2

Affiliations:

1Tenure-Track Program for Innovative Research, University of Fukui, Japan

2Department of Applied Chemistry, Tokyo University of Science, Japan

 

Funding information

This work was supported by JSPS KAKENHI Grant Numbers JP23K13743 and JP21K05061.



Journal

Journal of the American Chemical Society

DOI

10.1021/jacs.4c00841

Method of Research

Experimental study

Subject of Research

Not applicable

Article Title

Palladium-Catalyzed anti-Michael-Type (Hetero)arylation of Acrylamides

Article Publication Date

22-May-2024

COI Statement

The authors declare no competing financial interest.

Share12Tweet8Share2ShareShareShare2

Related Posts

blank

Adolescent Psychedelic Use Linked to Personality Traits

August 7, 2025
blank

Opioid-Sparing Strategies for Children’s Perioperative Pain

August 7, 2025

Estimating Population Affinity in South African Forensics

August 7, 2025

RNA Modifications May Play a Role in the Onset of Autoimmune Disorders

August 7, 2025

POPULAR NEWS

  • blank

    Neuropsychiatric Risks Linked to COVID-19 Revealed

    76 shares
    Share 30 Tweet 19
  • Overlooked Dangers: Debunking Common Myths About Skin Cancer Risk in the U.S.

    61 shares
    Share 24 Tweet 15
  • Predicting Colorectal Cancer Using Lifestyle Factors

    46 shares
    Share 18 Tweet 12
  • Modified DASH Diet Reduces Blood Sugar Levels in Adults with Type 2 Diabetes, Clinical Trial Finds

    44 shares
    Share 18 Tweet 11

About

We bring you the latest biotechnology news from best research centers and universities around the world. Check our website.

Follow us

Recent News

F. Uniseptata Pigment Boosts Microbial Fuel Cell Power

Ultra-Precise Microfiber Thermometer for Hairy Skin

Adolescent Psychedelic Use Linked to Personality Traits

  • Contact Us

Bioengineer.org © Copyright 2023 All Rights Reserved.

Welcome Back!

Login to your account below

Forgotten Password?

Retrieve your password

Please enter your username or email address to reset your password.

Log In
No Result
View All Result
  • Homepages
    • Home Page 1
    • Home Page 2
  • News
  • National
  • Business
  • Health
  • Lifestyle
  • Science

Bioengineer.org © Copyright 2023 All Rights Reserved.