Site-Selective Deuteration of N-Heterocycles via Iridium-Catalyzed Hydrogen Isotope Exchange

被引：83

作者：

Kerr, William J. ^{[1
]}

Lindsay, David M. ^{[1
]}

Owens, Philippa K. ^{[1
]}

Reid, Marc ^{[1
]}

Tuttle, Tell ^{[1
]}

Campos, Sebastien ^{[2
]}

机构：

[1] Univ Strathclyde, WestCHEM, Dept Pure & Appl Chem, Glasgow G1 1XL, Lanark, Scotland

[2] GlaxoSmithKline R&D, Med Res Ctr, Stevenage SG1 2NY, Herts, England

来源：

ACS CATALYSIS | 2017年 / 7卷 / 10期

基金：

英国工程与自然科学研究理事会;

关键词：

iridium; catalysis; indoles; isotope labeling; C-H activation; heterocycles; C-H ACTIVATION; INDOLES; COMPLEXES; PYRROLES; FUNCTIONALIZATION; ARYLATION; ALDEHYDES;

D O I：

10.1021/acscatal.7b02682

中图分类号：

O64 [物理化学（理论化学）、化学物理学];

学科分类号：

070304 ; 081704 ;

摘要：

The application of iridium(I) NHC/phosphine catalysts has delivered highly selective deuteration of indole, azaindole, and pyrrole N-heterocycles, which represent an important and relatively underexplored class of labeling substrates. Common N-protecting groups have been used to selectively direct C-H activation and can be removed under mild conditions with retention of the deuterium label. The method is exemplified by the labeling of the drug molecule sumatriptan. Complementary DFT studies have been conducted to facilitate the rationalization of the very good selectivity offered by the mild and convenient labeling process.

引用

页码：7182 / 7186

页数：5

共 42 条

[1]

[Anonymous], 2010, TOP HETEROCYCL CHEM

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

Atzrodt, Jens ;

Derdau, Volker ;

Fey, Thorsten ;

Zimmermann, Jochen .

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

[3] Expanded applicability of iridium(I) NHC/phosphine catalysts in hydrogen isotope exchange processes with pharmaceutically-relevant heterocycles [J].

Atzrodt, Jens ;

Derdau, Volker ;

Kerr, William J. ;

Reid, Marc ;

Rojahn, Patrick ;

Weck, Remo .

TETRAHEDRON, 2015, 71 (13) :1924-1929

[4] Pd-Catalyzed C-H Bond Functionalization on the Indole and Pyrrole Nucleus [J].

Beck, Elizabeth M. ;

Gaunt, Matthew J. .

C-H ACTIVATION, 2010, 292 :85-121

[5] Highly active iridium(I) complexes for catalytic hydrogen isotope exchange [J].

Brown, Jack A. ;

Irvine, Stephanie ;

Kennedy, Alan R. ;

Kerr, William J. ;

Andersson, Shalini ;

Nilsson, Goeran N. .

CHEMICAL COMMUNICATIONS, 2008, (09) :1115-1117

[6] The Synthesis of Highly Active Iridium(I) Complexes and their Application in Catalytic Hydrogen Isotope Exchange [J].

Brown, Jack A. ;

Cochrane, Alison R. ;

Irvine, Stephanie ;

Kerr, William J. ;

Mondal, Bhaskar ;

Parkinson, John A. ;

Paterson, Laura C. ;

Reid, Marc ;

Tuttle, Tell ;

Andersson, Shalini ;

Nilsson, Goran N. .

ADVANCED SYNTHESIS & CATALYSIS, 2014, 356 (17) :3551-3562

[7] LITHIATIONS OF 1-TRIALKYLSILYLPYRROLES - N TO C SILYL GROUP REARRANGEMENT [J].

CHADWICK, DJ ;

HODGSON, ST .

JOURNAL OF THE CHEMICAL SOCIETY-PERKIN TRANSACTIONS 1, 1982, (08) :1833-1836

[8] Practically convenient and industrially-aligned methods for iridium-catalysed hydrogen isotope exchange processes [J].

Cochrane, A. R. ;

Idziak, C. ;

Kerr, W. J. ;

Mondal, B. ;

Paterson, L. C. ;

Tuttle, T. ;

Andersson, S. ;

Nilsson, G. N. .

ORGANIC & BIOMOLECULAR CHEMISTRY, 2014, 12 (22) :3598-3603

[9] Application of neutral iridium(I) N-heterocyclic carbene complexes in ortho-directed hydrogen isotope exchange [J].

Cochrane, Alison R. ;

Irvine, Stephanie ;

Kerr, William J. ;

Reid, Marc ;

Andersson, Shalini ;

Nilsson, Goeran N. .

JOURNAL OF LABELLED COMPOUNDS & RADIOPHARMACEUTICALS, 2013, 56 (9-10) :451-454

[10] IRIDIUM COMPOUNDS IN CATALYSIS [J].

CRABTREE, R .

ACCOUNTS OF CHEMICAL RESEARCH, 1979, 12 (09) :331-338

← 1 2 3 4 5 →