Sterically Hindered Ketones via Palladium-Catalyzed Suzuki-Miyaura Cross-Coupling of Amides by N-C(O) Activation

Chengwei Liu; Roger Lalancette; Roman Szostak; Michal Szostak

doi:10.1021/acs.orglett.9b02961

Sterically Hindered Ketones via Palladium-Catalyzed Suzuki-Miyaura Cross-Coupling of Amides by N-C(O) Activation

Chengwei Liu, Roger Lalancette, Roman Szostak, Michal Szostak

Rutgers Newark, Chemistry

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

25 Scopus citations

Abstract

Herein, we report a new protocol for the synthesis of sterically hindered ketones that proceeds via palladium-catalyzed Suzuki-Miyaura cross-coupling of unconventional amide electrophiles by selective N-C(O) activation. Mechanistic studies demonstrate that steric bulk on the amide has a major impact, which is opposite to the traditional Suzuki-Miyaura cross-coupling of sterically hindered aryl halides. Structural and computational studies provide insight into ground-state distortion of sterically hindered amides and show that ortho-substitution alleviates the N-C(O) bond twist.

Original language	English (US)
Pages (from-to)	7976-7981
Number of pages	6
Journal	Organic letters
Volume	21
Issue number	19
DOIs	https://doi.org/10.1021/acs.orglett.9b02961
State	Published - Oct 4 2019

All Science Journal Classification (ASJC) codes

Biochemistry
Physical and Theoretical Chemistry
Organic Chemistry

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10.1021/acs.orglett.9b02961

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title = "Sterically Hindered Ketones via Palladium-Catalyzed Suzuki-Miyaura Cross-Coupling of Amides by N-C(O) Activation",

abstract = "Herein, we report a new protocol for the synthesis of sterically hindered ketones that proceeds via palladium-catalyzed Suzuki-Miyaura cross-coupling of unconventional amide electrophiles by selective N-C(O) activation. Mechanistic studies demonstrate that steric bulk on the amide has a major impact, which is opposite to the traditional Suzuki-Miyaura cross-coupling of sterically hindered aryl halides. Structural and computational studies provide insight into ground-state distortion of sterically hindered amides and show that ortho-substitution alleviates the N-C(O) bond twist.",

author = "Chengwei Liu and Roger Lalancette and Roman Szostak and Michal Szostak",

note = "Funding Information: The Bruker 500 MHz spectrometer was supported by an NSF-MRI grant (CHE-1229030). We thank the Wroclaw Center for Networking and Supercomputing (Grant No. WCSS159).*%blankline%* Funding Information: Rutgers University and the NSF (CAREER CHE-1650766) are gratefully acknowledged for support. The Bruker 500 MHz spectrometer was supported by an NSF-MRI grant (CHE-1229030). We thank the Wroclaw Center for Networking and Supercomputing (Grant No. WCSS159). Publisher Copyright: {\textcopyright} 2019 American Chemical Society.",

year = "2019",

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doi = "10.1021/acs.orglett.9b02961",

language = "English (US)",

volume = "21",

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T1 - Sterically Hindered Ketones via Palladium-Catalyzed Suzuki-Miyaura Cross-Coupling of Amides by N-C(O) Activation

AU - Liu, Chengwei

AU - Lalancette, Roger

AU - Szostak, Roman

AU - Szostak, Michal

N1 - Funding Information: The Bruker 500 MHz spectrometer was supported by an NSF-MRI grant (CHE-1229030). We thank the Wroclaw Center for Networking and Supercomputing (Grant No. WCSS159).*%blankline%* Funding Information: Rutgers University and the NSF (CAREER CHE-1650766) are gratefully acknowledged for support. The Bruker 500 MHz spectrometer was supported by an NSF-MRI grant (CHE-1229030). We thank the Wroclaw Center for Networking and Supercomputing (Grant No. WCSS159). Publisher Copyright: © 2019 American Chemical Society.

PY - 2019/10/4

Y1 - 2019/10/4

N2 - Herein, we report a new protocol for the synthesis of sterically hindered ketones that proceeds via palladium-catalyzed Suzuki-Miyaura cross-coupling of unconventional amide electrophiles by selective N-C(O) activation. Mechanistic studies demonstrate that steric bulk on the amide has a major impact, which is opposite to the traditional Suzuki-Miyaura cross-coupling of sterically hindered aryl halides. Structural and computational studies provide insight into ground-state distortion of sterically hindered amides and show that ortho-substitution alleviates the N-C(O) bond twist.

AB - Herein, we report a new protocol for the synthesis of sterically hindered ketones that proceeds via palladium-catalyzed Suzuki-Miyaura cross-coupling of unconventional amide electrophiles by selective N-C(O) activation. Mechanistic studies demonstrate that steric bulk on the amide has a major impact, which is opposite to the traditional Suzuki-Miyaura cross-coupling of sterically hindered aryl halides. Structural and computational studies provide insight into ground-state distortion of sterically hindered amides and show that ortho-substitution alleviates the N-C(O) bond twist.

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JO - Organic letters

JF - Organic letters

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ER -

Sterically Hindered Ketones via Palladium-Catalyzed Suzuki-Miyaura Cross-Coupling of Amides by N-C(O) Activation

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