C-4 Regioselective Alkylation of Pyridines Driven by Mechanochemically Activated Magnesium Metal

被引：14

作者：

Wu, Chongyang ^{[1
]}

Ying, Tao ^{[1
]}

Fan, Hangqian ^{[1
]}

Hu, Chenhui ^{[1
]}

Su, Weike ^{[1
]}

Yu, Jingbo ^{[1
]}

机构：

[1] Zhejiang Univ Technol, Key Lab Pharmaceut Engn Zhejiang Prov, Collaborat Innovat Ctr Yangtze River Delta Reg Gr, Hangzhou 310014, Peoples R China

来源：

ORGANIC LETTERS | 2023年 / 25卷 / 14期

基金：

中国国家自然科学基金; 国家重点研发计划;

关键词：

GRIGNARD;

D O I：

10.1021/acs.orglett.3c00684

中图分类号：

O62 [有机化学];

学科分类号：

070303 ; 081704 ;

摘要：

Mechanochemically activated magnesium(0) metal as a highly active mediator driving direct C-4-H alkylation of pyridines with alkyl halides has been developed. Excellent regioselectivity and substrate scope, including those containing reducible functionalities, free amines, and alcohols, as well as biologically relevant molecules were achieved to access 4-alkylpyridine products. Preliminary mechanistic studies suggested a radical-radical coupling pathway.

引用

页码：2531 / 2536

页数：6

共 35 条

[1] Reactions between Grignard reagents and heterocyclic N-oxides: Stereoselective synthesis of substituted pyridines, piperidines, and piperazines
Andersson, Hans
Olsson, Roger
Almqvist, Fredrik
[J]. ORGANIC & BIOMOLECULAR CHEMISTRY, 2011, 9 (02) : 337 - 346
[2] Cobalt-Catalyzed C4-Selective Direct Alkylation of Pyridines
Andou, Takashi
Saga, Yutaka
Komai, Hirotomo
Matsunaga, Shigeki
Kanai, Motomu
[J]. ANGEWANDTE CHEMIE-INTERNATIONAL EDITION, 2013, 52 (11) : 3213 - 3216
[3] ORGANOMETALLIC COMPOUNDS OF GROUP-2 .7. PREPARATION OF 4-ALKYLPYRIDINES BY REACTIONS OF SOME LIGHT-METALS WITH ALKYL-HALIDES IN PYRIDINE
BRYCESMITH, D
MORRIS, PJ
WAKEFIELD, BJ
[J]. JOURNAL OF THE CHEMICAL SOCIETY-PERKIN TRANSACTIONS 1, 1976, (18): : 1977 - 1983
[4] Synthesis of Pyridine and Dihydropyridine Derivatives by Regio- and Stereoselective Addition to N-Activated Pyridines
Bull, James A.
Mousseau, James J.
Pelletier, Guillaume
Charette, Andre B.
[J]. CHEMICAL REVIEWS, 2012, 112 (05) : 2642 - 2713
[5] Mechanochemical Activation of Zinc and Application to Negishi Cross-Coupling
Cao, Qun
Howard, Joseph L.
Wheatley, Emilie
Browne, Duncan L.
[J]. ANGEWANDTE CHEMIE-INTERNATIONAL EDITION, 2018, 57 (35) : 11339 - 11343
[6] STERIC EFFECTS .1. ESTERIFICATION AND ACID-CATALYZED HYDROLYSIS OF ESTERS
CHARTON, M
[J]. JOURNAL OF THE AMERICAN CHEMICAL SOCIETY, 1975, 97 (06) : 1552 - 1556
[7] Transition-Metal-Free BF3-Mediated Regioselective Direct Alkylation and Arylation of Functionalized Pyridines Using Grignard or Organozinc Reagents
Chen, Quan
du Jourdin, Xavier Mollat
Knochel, Paul
[J]. JOURNAL OF THE AMERICAN CHEMICAL SOCIETY, 2013, 135 (13) : 4958 - 4961
[8] Practical and Regioselective Synthesis of C-4-Alkylated Pyridines
Choi, Jin
Laudadio, Gabriele
Godineau, Edouard
Baran, Phil S.
[J]. JOURNAL OF THE AMERICAN CHEMICAL SOCIETY, 2021, 143 (31) : 11927 - 11933
[9] Efficacy, Pharmacodynamics, and Safety of VX-702, a Novel p38 MAPK Inhibitor, in Rheumatoid Arthritis Results of Two Randomized, Double-Blind, Placebo-Controlled Clinical Studies
Damjanov, Nemanja
Kauffman, Robert S.
Spencer-Green, George T.
[J]. ARTHRITIS AND RHEUMATISM, 2009, 60 (05): : 1232 - 1241
[10] Mechanochemistry for Synthesis
Friscic, Tomislav
Mottillo, Cristina
Titi, Hatem M.
[J]. ANGEWANDTE CHEMIE-INTERNATIONAL EDITION, 2020, 59 (03) : 1018 - 1029

← 1 2 3 4 →