Four-Selective Pyridine Alkylation via Wittig Olefination of Dearomatized Pyridylphosphonium Ylides

被引：17

作者：

Fricke, Patrick J. ^{[1
]}

Dolewski, Ryan D. ^{[1
]}

McNally, Andrew ^{[1
]}

机构：

[1] Colorado State Univ, Dept Chem, Ft Collins, CO 80523 USA

来源：

ANGEWANDTE CHEMIE-INTERNATIONAL EDITION | 2021年 / 60卷 / 39期

基金：

美国国家科学基金会;

关键词：

C-H functionalization; phosphonium salts; pyridine alkylation; pyridines; Wittig reaction; ALKYLIDENE DIHYDROPYRIDINES; FUNCTIONALIZATION; METHYLATION; SUBSTITUTION; HETEROCYCLES; FLUORINATION; DISCOVERY;

D O I：

10.1002/anie.202109271

中图分类号：

O6 [化学];

学科分类号：

0703 ;

摘要：

Methods to synthesize alkylated pyridines are valuable because these structures are prevalent in pharmaceuticals and agrochemicals. We have developed a distinct approach to construct 4-alkylpyridines using dearomatized pyridylphosphonium ylide intermediates in a Wittig olefination-rearomatization sequence. Pyridine N-activation is key to this strategy, and N-triazinylpyridinium salts enable coupling between a wide variety of substituted pyridines and aldehydes. The alkylation protocol is viable for late-stage functionalization, including methylation of pyridine-containing drugs. This approach represents an alternative to metal-catalyzed sp(2)-sp(3) cross-coupling reactions and Minisci-type processes.

引用

页码：21283 / 21288

页数：6

共 48 条

[21] Practical and innate carbon-hydrogen functionalization of heterocycles [J].

Fujiwara, Yuta ;

Dixon, Janice A. ;

O'Hara, Fionn ;

Funder, Erik Daa ;

Dixon, Darryl D. ;

Rodriguez, Rodrigo A. ;

Baxter, Ryan D. ;

Herle, Bart ;

Sach, Neal ;

Collins, Michael R. ;

Ishihara, Yoshihiro ;

Baran, Phil S. .

NATURE, 2012, 492 (7427) :95-+

[22] Asymmetric Cu-Catalyzed 1,4-Dearomatization of Pyridines and Pyridazines without Preactivation of the Heterocycle or Nucleophile [J].

Gribble, Michael W., Jr. ;

Guo, Sheng ;

Buchwald, Stephen L. .

JOURNAL OF THE AMERICAN CHEMICAL SOCIETY, 2018, 140 (15) :5057-5060

[23] Rhodium catalysed C-3/5 methylation of pyridines using temporary dearomatisation [J].

Grozavu, Alexandru ;

Hepburn, Hamish B. ;

Bailey, Elliot P. ;

Lindsay-Scott, Peter J. ;

Donohoe, Timothy J. .

CHEMICAL SCIENCE, 2020, 11 (32) :8595-8599

[24] Recent Developments in Negishi Cross-Coupling Reactions [J].

Haas, Diana ;

Hammann, Jeffrey M. ;

Greiner, Robert ;

Knochel, Paul .

ACS CATALYSIS, 2016, 6 (03) :1540-1552

[25] Coupling of Challenging Heteroaryl Halides with Alkyl Halides via Nickel-Catalyzed Cross-Electrophile Coupling [J].

Hansen, Eric C. ;

Li, Changfeng ;

Yang, Sihang ;

Pedro, Dylan ;

Weix, Daniel J. .

JOURNAL OF ORGANIC CHEMISTRY, 2017, 82 (14) :7085-7092

[26] Selective Functionalization of Pyridines via Heterocyclic Phosphonium Salts [J].

Hilton, Michael C. ;

Dolewski, Ryan D. ;

McNally, Andrew .

JOURNAL OF THE AMERICAN CHEMICAL SOCIETY, 2016, 138 (42) :13806-13809

[27] Advances in Transition Metal (Pd,Ni,Fe)-Catalyzed Cross-Coupling Reactions Using Alkyl-organometallics as Reaction Partners [J].

Jana, Ranjan ;

Pathak, Tejas P. ;

Sigman, Matthew S. .

CHEMICAL REVIEWS, 2011, 111 (03) :1417-1492

[28] Alcohols as alkylating agents in heteroarene C-H functionalization [J].

Jin, Jian ;

MacMillan, David W. C. .

NATURE, 2015, 525 (7567) :87-90

[29] Construction of 1,2,4-Triazole Derivatives via Cyclocondensation of Alkylidene Dihydropyridines and Aryldiazonium Salts [J].

Joshi, Madhur S. ;

Pigge, F. Christopher .

ORGANIC LETTERS, 2016, 18 (22) :5916-5919

[30] Dearomatized Alkylidene Dihydropyridines as Substrates for Mizoroki-Heck Cyclizations [J].

Joshi, Madhur S. ;

Pigge, F. Christopher .

ACS CATALYSIS, 2016, 6 (07) :4465-4469

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