DA Click Reaction

In 1928, Otto Diels and Kurt Alder discovered the Diels-Alder (DA) click reaction, an organic reaction used to convert a conjugated diene (a molecule with two alternating double bonds) and a substituted alkene (dienophile) to form a substituted cyclohexene derivative. It is a typical example of a pericyclic reaction with a concerted mechanism, and is classified as a thermally-allowed [4+2] cycloaddition with the Woodward-Hoffmann symbol [π4s+π2s]. DA click reaction is one of the most powerful reactions that introduce chemical complexity in the synthesis of natural products and new materials. The schematic diagram of the DA click reaction is shown in scheme 1.

Scheme 1. Schematic diagram of the DA click reaction.

Essential Characteristics

DA click reaction has the following essential characteristics:

• DA click reaction always can obtain a new six-membered ring.
• The conjugated diene component must be able to assume a s-cis conformation.
• DA click reaction is stereospecific with respect to substituent configuration in both conjugated dienes and dienophiles.
• Electron withdrawing groups on conjugated dienes and electron donating groups on dienophiles facilitate the DA click reaction.

Stereochemistry

In terms of stereochemistry, DA click reaction has regioselectivity, stereospecificity, and stereoselectivity.

• Regioselectivity:

DA click reaction is highly regioselective and follows the "ortho-para rule". That is, the mutual position between functional groups on a six-membered ring (assuming two functional groups) is mainly ortho or para.

• Stereospecificity:

DA click reaction is highly stereospecific. In simple terms, the configurations of conjugated dienes and dienophiles are retained in the end product.

• Stereoselectivity:

DA click reaction is highly stereoselective. Although it is generally more spatially congested, the endo transition state is typically preferred. This preference is known as the "Alder Endo" rule.

Mechanism

DA click reaction is a one-step concerted pericyclic reaction thought to occur through a single-ring transition, and no intermediates are generated during the reaction. This can be explained by an interaction between the highest occupied molecular orbital (LUMO) of electron-rich conjugated diene and the lowest unoccupied molecular orbital (LUMO) of electron-deficient dienophile. This interaction leads to the transition state having no additional orbital symmetry-imposed energetic barrier and allows the DA click reaction to occur easily.

What Can We Do?

As a leading customer-focused company, Alfa Chemistry has experienced experts and professional R & D laboratories. For many years, we have been focusing on reagent development and potential application exploration of the DA click reaction. If you have questions about the DA click reaction, please contact us. We will draw upon our wide range of advantages and high-quality products to create customized, scalable, efficient solutions for your research.