Pd-Catalyzed Chemoselective O-Benzylation of Ambident 2-Quinolinone Nucleophiles

Melissa Cadena; Roberto Silva Villatoro; Jyoti Shah Gupta; Cody Phillips; Jonathan B. Allen; Hadi D. Arman; Daniel J. Wherritt; Nicholas A. Clanton; Alexander L. Ruchelman; Eric M. Simmons; Albert J. Delmonte; John R. Coombs; Doug E. Frantz

doi:10.1021/acscatal.2c02783

Pd-Catalyzed Chemoselective O-Benzylation of Ambident 2-Quinolinone Nucleophiles

Melissa Cadena
, Roberto Silva Villatoro
, Jyoti Shah Gupta
, Cody Phillips
, Jonathan B. Allen
, Hadi D. Arman
, Daniel J. Wherritt
, Nicholas A. Clanton
, Alexander L. Ruchelman
, Eric M. Simmons
, Albert J. Delmonte
, John R. Coombs
, Doug E. Frantz

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

10 Scopus citations

Abstract

We have discovered and developed a highly chemoselective O-benzylation of ambident 2-quinolinone nucleophiles via Pd-catalysis. Detailed reaction analysis using direct-injection high resolution mass spectrometry (DI-HRMS) combined with in situ 31P NMR implicate a phosphine mono-oxide Pd(II) η1-benzyl complex as a key intermediate on the catalytic cycle. Extrapolation of this method to selectively O-alkylate a series of substituted 2-quinolinones using several benzylic electrophiles is demonstrated providing 2-benzyloxy quinolines in good yields and high O:N selectivities (up to 100:1) utilizing as little as 1 mol % Pd-catalyst to achieve these results.

Original language	English
Pages (from-to)	10199-10206
Number of pages	8
Journal	ACS Catalysis
Volume	12
Issue number	16
DOIs	https://doi.org/10.1021/acscatal.2c02783
State	Published - Aug 19 2022

Keywords

2-quinolinones
ambident nucleophiles
catalytic alkylation
chemoselectivity
Pd-catalysis

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10.1021/acscatal.2c02783

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@article{a580f2ae180e4dc58d5fccae78f18fc2,

title = "Pd-Catalyzed Chemoselective O-Benzylation of Ambident 2-Quinolinone Nucleophiles",

abstract = "We have discovered and developed a highly chemoselective O-benzylation of ambident 2-quinolinone nucleophiles via Pd-catalysis. Detailed reaction analysis using direct-injection high resolution mass spectrometry (DI-HRMS) combined with in situ 31P NMR implicate a phosphine mono-oxide Pd(II) η1-benzyl complex as a key intermediate on the catalytic cycle. Extrapolation of this method to selectively O-alkylate a series of substituted 2-quinolinones using several benzylic electrophiles is demonstrated providing 2-benzyloxy quinolines in good yields and high O:N selectivities (up to 100:1) utilizing as little as 1 mol \% Pd-catalyst to achieve these results.",

keywords = "2-quinolinones, ambident nucleophiles, catalytic alkylation, chemoselectivity, Pd-catalysis",

author = "Melissa Cadena and Villatoro, \{Roberto Silva\} and Gupta, \{Jyoti Shah\} and Cody Phillips and Allen, \{Jonathan B.\} and Arman, \{Hadi D.\} and Wherritt, \{Daniel J.\} and Clanton, \{Nicholas A.\} and Ruchelman, \{Alexander L.\} and Simmons, \{Eric M.\} and Delmonte, \{Albert J.\} and Coombs, \{John R.\} and Frantz, \{Doug E.\}",

note = "Publisher Copyright: {\textcopyright} 2022 American Chemical Society.",

year = "2022",

month = aug,

day = "19",

doi = "10.1021/acscatal.2c02783",

language = "English",

volume = "12",

pages = "10199--10206",

journal = "ACS Catalysis",

issn = "2155-5435",

number = "16",

}

TY - JOUR

T1 - Pd-Catalyzed Chemoselective O-Benzylation of Ambident 2-Quinolinone Nucleophiles

AU - Cadena, Melissa

AU - Villatoro, Roberto Silva

AU - Gupta, Jyoti Shah

AU - Phillips, Cody

AU - Allen, Jonathan B.

AU - Arman, Hadi D.

AU - Wherritt, Daniel J.

AU - Clanton, Nicholas A.

AU - Ruchelman, Alexander L.

AU - Simmons, Eric M.

AU - Delmonte, Albert J.

AU - Coombs, John R.

AU - Frantz, Doug E.

PY - 2022/8/19

Y1 - 2022/8/19

N2 - We have discovered and developed a highly chemoselective O-benzylation of ambident 2-quinolinone nucleophiles via Pd-catalysis. Detailed reaction analysis using direct-injection high resolution mass spectrometry (DI-HRMS) combined with in situ 31P NMR implicate a phosphine mono-oxide Pd(II) η1-benzyl complex as a key intermediate on the catalytic cycle. Extrapolation of this method to selectively O-alkylate a series of substituted 2-quinolinones using several benzylic electrophiles is demonstrated providing 2-benzyloxy quinolines in good yields and high O:N selectivities (up to 100:1) utilizing as little as 1 mol % Pd-catalyst to achieve these results.

AB - We have discovered and developed a highly chemoselective O-benzylation of ambident 2-quinolinone nucleophiles via Pd-catalysis. Detailed reaction analysis using direct-injection high resolution mass spectrometry (DI-HRMS) combined with in situ 31P NMR implicate a phosphine mono-oxide Pd(II) η1-benzyl complex as a key intermediate on the catalytic cycle. Extrapolation of this method to selectively O-alkylate a series of substituted 2-quinolinones using several benzylic electrophiles is demonstrated providing 2-benzyloxy quinolines in good yields and high O:N selectivities (up to 100:1) utilizing as little as 1 mol % Pd-catalyst to achieve these results.

KW - 2-quinolinones

KW - ambident nucleophiles

KW - catalytic alkylation

KW - chemoselectivity

KW - Pd-catalysis

UR - https://www.scopus.com/pages/publications/85135977899

U2 - 10.1021/acscatal.2c02783

DO - 10.1021/acscatal.2c02783

M3 - Article

AN - SCOPUS:85135977899

SN - 2155-5435

VL - 12

SP - 10199

EP - 10206

JO - ACS Catalysis

JF - ACS Catalysis

IS - 16

ER -

Pd-Catalyzed Chemoselective O-Benzylation of Ambident 2-Quinolinone Nucleophiles

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Keywords

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