Catalysis

Photosensitized Nickel Catalysis Enabled Silyl Radical Mediated Direct Activation of Carbamoyl Chlorides to Access (Hetero)aryl Carbamides

Authors

Abstract

The transformation of a readily available molecule to a medicinally relevant functionality is the heart of organic synthesis which literally unfolds new direction in the field of drug discovery and development. Accordingly, synthetic chemistry fraternity is constantly striving to introduce a range of avant-garde techniques to construct an incredibly important fundamental entity like “amide bonds” which connect the amino acids in proteins and exist as a prevalent structural motif in biomolecules. In this context, we want to introduce the concept of cross-electrophile coupling by merging the photoredox and transition metal catalysis to construct carbamides from superabundant (hetero)aryl chlorides or bromides along with commercially feasible carbamoyl chlorides. However, there is barely any report on direct activation of carbamoyl chloride so far. To circumvent the challenge, we employ the intrinsic affinity of silyl radical species towards halogen atom to harness the carbamoyl radical directly from carbamoyl chlorides which is seemingly the first of its kind. The success of this protocol relies on the prior formation of ‘aryl halides to Ni-catalyst’ oxidative addition intermediate that assists in generation of the vital carbamoyl radical. The breadth of application of this technique is significantly demonstrated by the synthesis of a plethora of (hetero)aryl carbamides with diverse functionalities. As stated earlier, we outline the direct utility of this protocol by the late-stage amidation of halide containing drug molecules and pharmacophores.

Content

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Supplementary material

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Photosensitized Nickel Catalysis Enabled Silyl Radical Mediated Direct Activation of Carbamoyl Chlorides to Access (Hetero)aryl Carbamides
Supplementary Information

Supplementary weblinks

DM Lab, IIT Bombay
DM Lab, IIT Bombay