摘要：Department of Chemical Science and Engineering, Kobe University, Kobe 657-8501, Japan;

转自：康龙化成

Regioselective Deprotonative Metalation of Heteroarenes with a Combination of Lithium Amide and Zinc Chloride Diamine Complex

Yuxuan Feng, Atsunori Mori, and Kentaro Okano*

Department of Chemical Science and Engineering, Kobe University, Kobe 657-8501, Japan;

Research Center for Membrane and Film Technology, Kobe University, Kobe 657-8501, Japan

—doi.org/10.1021/acs.joc.5c01171

Recommended by Feng Wang_SC

KEYWORDS:metalation (反应类型), heteroarenes,LiTMP, ZnCl2· TMEDA(原料), 2-substituted heteroarenes (产物), C(sp2)-Zn, C(sp2)-C(sp3), C(sp2)-C(sp2), C(sp2)-S, C(sp2)-I (成键类型), thermodynamically favorable (其他)

ABSTRACT:A method for the C-2-selective deprotonative functionalization of halopyridines and other heteroarenes is described. The heteroaryllithium species generated by kinetic deprotonation is trapped by a zinc chloride diamine complex to form the heteroarylzinc species at room temperature. In this transformation, thermodynamically favorable competing reactions, including intermolecular proton transfer, halogen dance, andaryneformation, are suppressed. The resulting organozinc species were treated with electrophiles to afford the corresponding products in 44%−96% yields.

This work

Summary and comments

In conclusion, Prof. Okano et al. have developed a mild and efficientprotocol for the C-2 selective deprotonative metalation of heteroarenesusing a combination of LiTMP and ZnCl2· TMEDA. This protocol allows the conversion of hetero-aryllithium species generated by kinetic deprotonation into stable organozincspecies at room temperature. Furthermore, the products can subsequently react with several electrophiles to achieve diverse structural modifications. This is the first report enabling deprotonative functionalization of 3-iodopyridine.A wide range of C-2 iodinated heteroarenes, thus synthesized in this study, serve as promising intermediates for the further construction of C−C and C−N bonds via reliable cross-coupling reactions, expanding the synthetic toolbox for drug and agrochemical discovery based on heterocyclic scaffolds.

来源：新浪财经