A facile and general acid-catalyzed deuteration at methyl groups of N-heteroarylmethanes

被引：47

作者：

Liu, Min ^{[1
]}

Chen, Xue ^{[1
]}

Chen, Tieqiao ^{[1
]}

Yin, Shuang-Feng ^{[1
]}

机构：

[1] Hunan Univ, Coll Chem & Chem Engn, State Key Lab Chemo Biosensing & Chemometr, Changsha 410082, Hunan, Peoples R China

来源：

ORGANIC & BIOMOLECULAR CHEMISTRY | 2017年 / 15卷 / 12期

关键词：

C-H ACTIVATION; H/D EXCHANGE; ACRIDONE ALKALOIDS; DISCOVERY; DEUTERIUM; INHIBITORS; QUINAZOLINE; OXIDATION; QUINOLINE; BONDS;

D O I：

10.1039/c7ob00062f

中图分类号：

O62 [有机化学];

学科分类号：

070303 ; 081704 ;

摘要：

A facile and general Bronsted acid-catalyzed deuteration at the methyl group of N-heteroarylmethanes was achieved through a dearomatic enamine intermediate under relatively mild reaction conditions. Both 2-methyl and 4-methyl groups in quinolines were deuterated with high deuterium incorporation. Pyridines, benzo[d] thiazoles, indoles and imines including these clinical drugs were also deuterated efficiently at the methyl groups. This reaction could be conducted on a large scale (500 mmol), showing its good potential for use in large-scale synthesis.

引用

页码：2507 / 2511

页数：5

共 53 条

[1]

[Anonymous], 1987, MECH THEORY ORGANIC

[2] Deuteration enhances catalyst lifetime in palladium-catalysed alcohol oxidation [J].

Armenise, Nicola ;

Tahiri, Nabil ;

Eisink, Niek N. H. M. ;

Denis, Mathieu ;

Jager, Manuel ;

De Vries, Johannes G. ;

Witte, Martin D. ;

Minnaard, Adriaan J. .

CHEMICAL COMMUNICATIONS, 2016, 52 (10) :2189-2191

[3] The renaissance of H/D exchange [J].

Atzrodt, Jens ;

Derdau, Volker ;

Fey, Thorsten ;

Zimmermann, Jochen .

ANGEWANDTE CHEMIE-INTERNATIONAL EDITION, 2007, 46 (41) :7744-7765

[4] The Methylation Effect in Medicinal Chemistry [J].

Barreiro, Eliezer J. ;

Kuemmerle, Arthur E. ;

Fraga, Carlos A. M. .

CHEMICAL REVIEWS, 2011, 111 (09) :5215-5246

[5] Going Out on a Limb: Delineating The Effects of β-Branching, N-Methylation, and Side Chain Size on the Passive Permeability, Solubility, and Flexibility of Sanguinamide A Analogues [J].

Bockus, Andrew T. ;

Schwochert, Joshua A. ;

Pye, Cameron R. ;

Townsend, Chad E. ;

Sok, Vong ;

Bednarek, Maria A. ;

Lokey, R. Scott .

JOURNAL OF MEDICINAL CHEMISTRY, 2015, 58 (18) :7409-7418

[6] Identification of Clinically Viable Quinolinol Inhibitors of Botulinum Neurotoxin A Light Chain [J].

Caglic, Dejan ;

Krutein, Michelle C. ;

Bompiani, Kristin M. ;

Barlow, Deborah J. ;

Benoni, Galit ;

Pelletier, Jeffrey C. ;

Reitz, Allen B. ;

Lairson, Luke L. ;

Houseknecht, Karen L. ;

Smith, Garry R. ;

Dickerson, Tobin J. .

JOURNAL OF MEDICINAL CHEMISTRY, 2014, 57 (03) :669-676

[7] Site-selective Sp2 and benzylic Sp3 palladium-catalyzed direct arylation [J].

Campeau, Louis-Charles ;

Schipper, Derek J. ;

Fagnou, Keith .

JOURNAL OF THE AMERICAN CHEMICAL SOCIETY, 2008, 130 (11) :3266-+

[8] Selective Catalytic Deuterium Labeling of Alcohols during a Transfer Hydrogenation Process of Ketones Using D2O as the Only Deuterium Source. Theoretical and Experimental Demonstration of a Ru-H/D+ Exchange as the Key Step [J].

Carmen Carrion, M. ;

Ruiz-Castaneda, Margarita ;

Espino, Gustavo ;

Aliende, Cristina ;

Santos, Lucia ;

Rodriguez, Ana M. ;

Manzano, Blanca R. ;

Jalon, Felix A. ;

Lledos, Agusti .

ACS CATALYSIS, 2014, 4 (04) :1040-1053

[9] The ruthenium-catalysed selective synthesis of mono-deuterated terminal alkynes [J].

Chatterjee, Basujit ;

Gunanathan, Chidambaram .

CHEMICAL COMMUNICATIONS, 2016, 52 (24) :4509-4512

[10] Palladium-catalyzed alkylation of sp2 and sp3 C-H bonds with methylboroxine and alkylboronic acids:: Two distinct C-H activation pathways [J].

Chen, Xiao ;

Goodhue, Charles E. ;

Yu, Jin-Quan .

JOURNAL OF THE AMERICAN CHEMICAL SOCIETY, 2006, 128 (39) :12634-12635

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