"Exploring Suprafacial vs Antarafacial Sigmatropic Rearrangements: Differences, Mechanisms, and Applications in Total Synthesis of Natural Products, with a Focus on Computational Methods and Key Reactions"

 

"Exploring Suprafacial vs Antarafacial Sigmatropic Rearrangements: Differences, Mechanisms, and Applications in Total Synthesis of Natural Products, with a Focus on Computational Methods and Key Reactions"

Introduction:

Sigmatropic rearrangements are organic reactions in which a sigma bond is rearranged in a concerted manner. Suprafacial and antarafacial sigmatropic rearrangements are two important types of these reactions. In this article, we will explore the differences between suprafacial and antarafacial sigmatropic rearrangements, their mechanisms, and their applications in organic synthesis.

Differences between Suprafacial and Antarafacial Sigmatropic Rearrangements:

Suprafacial and antarafacial sigmatropic rearrangements differ in the way the sigma bond is broken and re-formed during the reaction. In suprafacial sigmatropic rearrangements, the breaking and forming of the sigma bond occurs on the same face of the molecule. In contrast, in antarafacial sigmatropic rearrangements, the breaking and forming of the sigma bond occurs on opposite faces of the molecule.

Mechanisms of Suprafacial and Antarafacial Sigmatropic Rearrangements:

Understanding the mechanisms of suprafacial and antarafacial sigmatropic rearrangements is crucial for their successful application in organic synthesis. There mechanisms are diverse. In suprafacial sigmatropic rearrangements, the reaction occurs through a cyclic transition state in which the sigma bond is broken and re-formed on the same face of the molecule. In antarafacial sigmatropic rearrangements, the reaction occurs through a linear transition state in which the sigma bond is broken and re-formed on opposite faces of the molecule.

Computational Methods Used in Studying Suprafacial and Antarafacial Sigmatropic Rearrangement:

Theoretical studies on suprafacial and antarafacial sigmatropic rearrangement mechanisms are typically carried out using computational methods such as density functional theory (DFT) and ab initio calculations. These theoretical studies have allowed for the prediction of reaction pathways, intermediates, and transition states, and have provided insights into the factors that influence the selectivity and stereoselectivity of these reactions. These insights have allowed for the design of new and more efficient reactions, and have enabled chemists to predict the outcome of reactions with greater accuracy. Furthermore, the computational methods used to study these reactions have the potential to accelerate the discovery of new chemical reactions and to reduce the need for trial and error in the laboratory.

Suprafacial and Antarafacial Sigmatropic Rearrangement in Total Natural Synthesis: Suprafacial and antarafacial sigmatropic rearrangements are key reactions in the total synthesis of natural products due to their ability to create multiple bonds and stereocenters in a single step. For example, suprafacial sigmatropic rearrangement was employed in the total synthesis of strychnine, a complex alkaloid found in plants. In this reaction, the vinyl group migrates from the right-hand side of the conjugated diene to the left-hand side, forming a new double bond and a triple bond. This reaction creates a key intermediate that can be further transformed into strychnine.

 In another example, antarafacial sigmatropic rearrangement was used in the synthesis of jatropholone A, a natural product with anticancer activity. In this reaction, the carbon group migrates from the right-hand side of the conjugated diene to the left-hand side, forming a new carbon-carbon bond. This reaction creates a bicyclic lactam ring system that is found in the structure of jatropholone A.

Applications of Suprafacial and Antarafacial Sigmatropic Rearrangements:

Suprafacial and antarafacial sigmatropic rearrangements have important applications in organic synthesis. Suprafacial sigmatropic rearrangements are commonly used in the synthesis of natural products, such as steroids, terpenes, and alkaloids. Antarafacial sigmatropic rearrangements are important in the synthesis of cyclic compounds, such as cyclooctatetraene and benzocyclobutene.

Conclusion:

Suprafacial and antarafacial sigmatropic rearrangements are two important types of organic reactions that differ in the way the sigma bond is broken and re-formed during the reaction. Understanding the mechanisms of these reactions is crucial for their successful application in organic synthesis. Suprafacial and antarafacial sigmatropic rearrangements have a wide range of applications in the synthesis of natural products and cyclic compounds, and their importance in organic chemistry continues to grow.