Chemoselective Synthesis of α-Amino-α-cyanophosphonates by Reductive Gem-Cyanation–Phosphonylation of Secondary Amides

Abstract

A novel approach to α-amino-α-cyanophosphonates has been developed. The method features a Tf 2 O-mediated reductive geminal cyanation/phosphonylation of secondary amides. Mild reaction conditions, high bond-forming efficiency, inexpensive readily available starting materials, and good to excellent yields with wide functional group compatibility constitute the main advantages of this method. The protocol can be run on a gram scale.

Asymmetric Spirocyclization Enabled by Iridium and Brønsted Acid-Catalyzed Formal Reductive Cycloaddition

“…23,24 In this context, owing to the stability of the amide group, the two-step process of amide reduction-activation and nucleophilic substitution or nucleophilic addition are generally involved. Therefore, stoichiometric activating agents or reductants, including triflic anhydride (Tf 2 O), [25][26][27] DIBAL-H, 28,29 Schwartz's reagent (Cp 2 ZrHCl), 30,31 and NaH 32 have been used to successfully motivate the reaction (Scheme 1b). And Tf 2 O-mediated formal reductive cycloadditions of amides with alkynes or alkenes in a one-pot manner to give azaheterocycles have been reported.…”

Triflic Anhydride (Tf2O)-Activated Transformations of Amides, Sulfoxides and Phosphorus Oxides via Nucleophilic Trapping

“…This strategy represents an efficient alternative method for the construction of α-amino-α-cyanophosphonic acid derivatives 33d (Scheme 33, eq 2). 66 Scheme 33. The phosphonylation of amides.…”

An efficient and straightforward approach for accessing thionoesters via palladium-catalyzed C–N cleavage of thioamides

“…Since the first report in 2015, 39 rapid and profound progress has been made on the selective C–N bond cleavage of activated amides via a transition-metal-catalyzed system. Szostak, 40–57 Garg, 58–68 Zou, 69–71 Yamaguchi, 72–76 Huang, 77–83 Shi, 84–86 and Rueping 87–89 have made great contributions to the study of amide transformation. Our group 90–105 has also conducted excellent research in this field.…”