Very recently, directing group (DG) migration has emerged as a practical strategy for transition-metal-catalysed direct C-H activation, resulting in a highly atom-economical process and enabling the reusage of DG. Therefore, great progress has been made in developing multitasking DGs. In this tutorial review, we present the rapid advances of this novel strategy by analyzing and comparing the different types of migratable DGs (including N-O, N-C, N-N or O-C bond cleavage to trigger DG migration). The related mechanisms, as well as synthetic applications, are also mentioned.

Directing group migration strategy in transition-metal-catalysed direct C–H functionalization

1,1,1,3,3,3-Hexafluoroisopropanol (HFIP) is a polar, strongly hydrogen bond-donating solvent that has found numerous uses in organic synthesis due to its ability to stabilize ionic species, transfer protons, and engage in a range of other intermolecular interactions. The use of this solvent has exponentially increased in the past decade and has become a solvent of choice in some areas, such as C-H functionalization chemistry. In this review, following a brief history of HFIP in organic synthesis and an overview of its physical properties, literature examples of organic reactions using HFIP as a solvent or an additive are presented, emphasizing the effect of solvent of each reaction.

HFIP in Organic Synthesis.

N-Nitrosamines are a class of compounds notorious both for the potent carcinogenicity of many of its members and for their widespread occurrence throughout the human environment, from air and water to our diets and drugs. Considerable effort has been dedicated to understanding N-nitrosamines as contaminants, and methods for their prevention, remediation, and detection are ongoing challenges. Understanding the chemistry of N-nitrosamines will be key to addressing these challenges. To facilitate such understanding, we focus in this Perspective on the structure, reactivity, and synthetic applications of N-nitrosamines with an emphasis on alkyl N-nitrosamines. The role of N-nitrosamines as water contaminants and the methods for their detection are also discussed.

An Organic Chemist's Guide to N-Nitrosamines: Their Structure, Reactivity, and Role as Contaminants.

Axially chiral open-chain olefins represent an underexplored class of chiral platform. In this report, two classes of tetrasubstituted axially chiral acyclic olefins have been accessed in excellent enantioselectivity and regioselectivity via C-H activation of (hetero)arenes assisted by a migratable directing group en route to coupling with sterically hindered alkynes. The coupling of indoles bearing an N-aminocarbonyl directing group afforded C-N axially chiral acrylamides with assistance of a racemic zinc carboxylate additive. DFT studies suggest a β-nitrogen elimination-reinsertion pathway for the directing group migration. Meanwhile, the employment of N-phenoxycarboxamide delivered C-C axially chiral enamides via migration of the oxidizing directing group. Experimental studies suggest that in both cases the (hetero)arene substrate adopts a well-defined orientation during the C-H activation, which in turn determines the disposition of alkyne in migratory insertion. Synthetic applications of representative chiral olefins have been demonstrated.

Rhodium-Catalyzed Atroposelective Access to Axially Chiral Olefins via C-H Bond Activation and Directing Group Migration

Rhodium(III)-Catalyzed [4+3] Annulation of N-Aryl-pyrazolidinones and Propargylic Acetates: Access to Benzo[c][1,2]diazepines

Rh(III)-Catalyzed Tandem Acylmethylation/Nitroso Migration/Cyclization of N-Nitrosoanilines with Sulfoxonium Ylides in One Pot: Approach to 3-Nitrosoindoles.

The invention belongs to the technical field of organic synthesis and particularly relates to a preparation method of a 3-nitroso substituted indole derivative. The preparation method comprises the following steps: mixing N-nitrosoaniline as shown in a formula II, acyl sulfur ylide as shown in a formula III, a catalyst, silver salt and a solvent, performing carbon-hydrogen bond activation reaction, adding protonic acid and performing cyclizing and cascaded nitroso migration reaction, wherein the catalyst is a compound of transition metal and the transition metal is at least one of rhodium, ruthenium, cobalt, iridium and palladium. The structural formula of the 3-nitroso substituted indole derivative prepared by the preparation method is as shown in a formula I. By the preparation method provided by the invention, synthesis of the indole derivative can be realized by mixing the raw materials through a one-pot method, so the preparation process is simple and easy to control.

Yingtao Wu

Papers

Directing group migration strategy in transition-metal-catalysed direct C–H functionalization

Rh(III)-Catalyzed Tandem Acylmethylation/Nitroso Migration/Cyclization of N-Nitrosoanilines with Sulfoxonium Ylides in One Pot: Approach to 3-Nitrosoindoles.

Preparation method of 3-nitroso substituted indole derivative