A general formamide-catalyzed protocol for the efficient transformation of alcohols into alkyl chlorides, which is promoted by substoichiometric amounts (down to 34 mol %) of inexpensive trichlorotriazine (TCT), is introduced. This is the first example of a TCT-mediated dihydroxychlorination of an OH-containing substrate (e.g., alcohols and carboxylic acids) in which all three chlorine atoms of TCT are transferred to the starting material. The consequently enhanced atom economy facilitates a significantly improved waste balance (E-factors down to 4), cost efficiency, and scalability (>50 g). Furthermore, the current procedure is distinguished by high levels of functional-group compatibility and stereoselectivity, as only weakly acidic cyanuric acid is released as exclusive byproduct. Finally, a one-pot protocol for the preparation of amines, azides, ethers, and sulfides enabled the synthesis of the drug rivastigmine with twofold S 2 inversion, which demonstrates the high practical value of the presented method.

Nucleophilic substitutions (S N ) at sp 3 -hybridized carbon centers are one of the most fundamental type of transformation in organic synthesis. Taking the importance of bimolecular S N reactions into account, catalytic variants must be considered as underdeveloped. This review highlights the most recent progress in the emerging field of Lewis base catalyzed S N -type transformations that are mediated by simple acid chlorides and anhydrides. 1 Introduction 2 Phosphine Oxide and Cyclopropenone Catalysis 3 Formamide Catalysis 4 Other Catalytic Systems 5 Conclusion

Coumaryl triflate can be used for a wide range of substitution reactions, either under Pd-catalyzed conditions or via direct nucleophilic substitutions, and is therefore an ideal substrate for the fluorescence labeling of functionalized compounds, such as amino acids.

Substitution reactions belong to the most fundamental transformations in chemistry. However, they are commonly restricted by a poor sustainability, as at least one waste byproduct is formed. Herein, a general and highly efficient formamide‐catalyzed method for nucleophilic substitution of alcohols furnishing alkyl chlorides is presented, in which the mass of the inevitable byproduct could be reduced to a minimum, through the application of inexpensive cyanuric chloride as reagent in substoichiometric amounts down to 34 mol % with respect to the starting material. Therefore, only one molecule of the reagent is required to convert three molecules of the starting alcohol. Application towards the synthesis of a bioactive compound is also demonstrated. (© Background graphic MrGarry/Shutterstock.com.) More information can be found in the Full Paper by P. H. Huy and I. Fillbrich on page 7410.