Direct Synthesis of α-Amino Nitriles from Sulfonamides via Base-Mediated C-H Cyanation

Shasha Shi; Xianyu Yang; Man Tang; Jiefeng Hu; Teck Peng Loh

doi:10.1021/acs.orglett.1c01232

Direct Synthesis of α-Amino Nitriles from Sulfonamides via Base-Mediated C-H Cyanation

Shasha Shi, Xianyu Yang, Man Tang, Jiefeng Hu^*, Teck Peng Loh^*

^*Corresponding author for this work

Research output: Contribution to journal › Article › peer-review

6 Citations (Scopus)

Abstract

Herein, we disclose a transition-metal-free reaction system that enables α-cyanation of sulfonamides through C-H bond cleavage for the preparation of α-amino nitriles, including difficult-to-access all-alkyl α-tertiary scaffolds. More than 50 substrate examples prove a wide functional group tolerance. Additionally, its synthetic practicality is highlighted by gram-scalability and the late-stage modification of natural compounds. Mechanistic experiments suggest that this process involves in situ formation of an imine intermediate via base-promoted elimination of HF.

Original language	English
Pages (from-to)	4018-4022
Number of pages	5
Journal	Organic Letters
Volume	23
Issue number	10
DOIs	https://doi.org/10.1021/acs.orglett.1c01232
Publication status	Published - May 21 2021
Externally published	Yes

Bibliographical note

Publisher Copyright:
© 2021 American Chemical Society.

ASJC Scopus Subject Areas

Biochemistry
Physical and Theoretical Chemistry
Organic Chemistry

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title = "Direct Synthesis of α-Amino Nitriles from Sulfonamides via Base-Mediated C-H Cyanation",

abstract = "Herein, we disclose a transition-metal-free reaction system that enables α-cyanation of sulfonamides through C-H bond cleavage for the preparation of α-amino nitriles, including difficult-to-access all-alkyl α-tertiary scaffolds. More than 50 substrate examples prove a wide functional group tolerance. Additionally, its synthetic practicality is highlighted by gram-scalability and the late-stage modification of natural compounds. Mechanistic experiments suggest that this process involves in situ formation of an imine intermediate via base-promoted elimination of HF.",

author = "Shasha Shi and Xianyu Yang and Man Tang and Jiefeng Hu and Loh, \{Teck Peng\}",

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doi = "10.1021/acs.orglett.1c01232",

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T1 - Direct Synthesis of α-Amino Nitriles from Sulfonamides via Base-Mediated C-H Cyanation

AU - Shi, Shasha

AU - Yang, Xianyu

AU - Tang, Man

AU - Hu, Jiefeng

AU - Loh, Teck Peng

PY - 2021/5/21

Y1 - 2021/5/21

N2 - Herein, we disclose a transition-metal-free reaction system that enables α-cyanation of sulfonamides through C-H bond cleavage for the preparation of α-amino nitriles, including difficult-to-access all-alkyl α-tertiary scaffolds. More than 50 substrate examples prove a wide functional group tolerance. Additionally, its synthetic practicality is highlighted by gram-scalability and the late-stage modification of natural compounds. Mechanistic experiments suggest that this process involves in situ formation of an imine intermediate via base-promoted elimination of HF.

AB - Herein, we disclose a transition-metal-free reaction system that enables α-cyanation of sulfonamides through C-H bond cleavage for the preparation of α-amino nitriles, including difficult-to-access all-alkyl α-tertiary scaffolds. More than 50 substrate examples prove a wide functional group tolerance. Additionally, its synthetic practicality is highlighted by gram-scalability and the late-stage modification of natural compounds. Mechanistic experiments suggest that this process involves in situ formation of an imine intermediate via base-promoted elimination of HF.

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JO - Organic Letters

JF - Organic Letters

IS - 10

ER -

Direct Synthesis of α-Amino Nitriles from Sulfonamides via Base-Mediated C-H Cyanation

Abstract

Bibliographical note

ASJC Scopus Subject Areas

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