Synthetic and Mechanistic Studies of a Versatile Heteroaryl Thioether Directing Group for Pd(II) Catalysis

A weakly coordinating monodentate heteroaryl thioether directing group has been developed for use in Pd(II) catalysis to orchestrate key elementary steps in the catalytic cycle that require conformational flexibility in a manner that is difficult to accomplish with traditional strongly coordinating directing groups. This benzothiazole thioether, (BT)S, directing group can be used to promote oxidative Heck reactivity of internal alkenes providing a wide range of products in moderate to high yields. To demonstrate the broad applicability of this directing group, arene C–H olefination was also successfully developed. Reaction progress kinetic analysis provides insights into the role of the directing group in each reaction, which is supplemented with computational data for the oxidative Heck reaction. Furthermore, this (BT)S directing group can be transformed into a number of synthetically useful functional groups, including a sulfone for Julia olefination, allowing it to serve as a “masked olefin” directing group in synthetic planning. In order to demonstrate this synthetic utility, natural products (+)-salvianolic acid A and salvianolic acid F are formally synthesized using the (BT)S directed C–H olefination as the key step.

Synthetic and Mechanistic Studies of a Versatile Heteroaryl Thioether Directing Group for Pd(II) Catalysis

A weakly coordinating monodentate heteroaryl thioether directing group has been developed for use in Pd(II) catalysis to orchestrate key elementary steps in the catalytic cycle that require conformational flexibility in a manner that is difficult to accomplish with traditional strongly coordinating directing groups. This benzothiazole thioether, (BT)S, directing group can be used to promote oxidative Heck reactivity of internal alkenes providing a wide range of products in moderate to high yields. To demonstrate the broad applicability of this directing group, arene C–H olefination was also successfully developed. Reaction progress kinetic analysis provides insights into the role of the directing group in each reaction, which is supplemented with computational data for the oxidative Heck reaction. Furthermore, this (BT)S directing group can be transformed into a number of synthetically useful functional groups, including a sulfone for Julia olefination, allowing it to serve as a “masked olefin” directing group in synthetic planning. In order to demonstrate this synthetic utility, natural products (+)-salvianolic acid A and salvianolic acid F are formally synthesized using the (BT)S directed C–H olefination as the key step.

Extension of the Modified Julia Olefination on Carboxylic Acid Derivatives: Scope and Applications

This account relates our work in the field of modified Julia olefination to extend this very useful olefination method to carboxylic acid derivatives. Since our preliminary results on lactones in 2005, the reaction has been extended to a large range of derivatives (lactams, imides and anhydrides) through an intra- or intermolecular process leading to a great variety of structures (enol ethers, enamides and exo enol esters). This article will also focus on the application of this methodology for the preparation of biologically interesting compounds and/or total syntheses of natural products such as C-disaccharide, bistramide A, jaspine B and maculalactone B.1 Introduction2 Modified Julia Olefination on Lactones2.1 Methylene Enol Ether Synthesis2.2 Substituted Enol Ether Synthesis2.3 Monofluorinated Enol Ether Synthesis2.4 Difluorinated Enol Ether Synthesis3 Applications3.1 Spiroketal Synthesis3.2 Spirocompound Synthesis3.3 Pseudodisaccharide Synthesis3.4 Total Synthesis of Jaspine B4 Modified Julia Olefination on Other Carboxylic Acid Derivatives4.1 Lactam Olefination and Spiroaminal Synthesis4.2 Bicyclic Enamide Synthesis by Intramolecular Modified Julia Olefination on Imides4.3 Modified Julia Olefination on Anhydrides5 Conclusion

Esterase-sensitive sulfur dioxide prodrugs inspired by modified Julia olefination

Esterase-triggered SO2prodrugs with tunable release rates.