Alkylation reaction at non-acidic saturated C-H bonds

2020 Fiscal Year Final Research Report

• Project/Area Number: 18K05107
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 33020:Synthetic organic chemistry-related
• Research Institution: Yamaguchi University
• Principal Investigator: Kamijo Shin 山口大学, 大学院創成科学研究科, 准教授 (00359548)
• Project Period (FY): 2018-04-01 – 2021-03-31
• Keywords: C-H官能基化 / ヘテロ芳香環導入 / アルキル化 / 光反応

Outline of Final Research Achievements

We have developed a new synthetic method that can achieve a one-step introduction of heteroaromatic compounds such as benzothiazole, benzoxazole, and benzimidazole, which are widely seen as partial components of pharmaceuticals and functional materials, into saturated heterocyclic compounds such as cyclic ethers, azacycles, and tetrahydrothiophene. The benzazole unit is site-selectively installed at the carbon center substituted with a heteroatom, such as oxygen, nitrogen, and sulfur, of the saturated heterocyclic compound.
Chemoselective hydrogen abstraction from saturated heterocycles with photo-excited ketones [radical cleavage of the heteroatom-substituted C(sp3)-H bond], generation of carbon radical species, addition of the carbon radicals to 2-sulfonylated benzazole, elimination of sulfonyl radical, and then the alkylated benzazole is derived as a product.

Free Research Field

有機合成化学

Academic Significance and Societal Importance of the Research Achievements

従来法では、近傍に電子求引性官能基が置換し、酸性度の高まったC(sp3)-H結合が、分子変換における反応点として注目されてきた。しかし、分子骨格を構成する炭素鎖上のC-H結合のうち、酸性度をもつものは限定的で、一般的には、反応性が低く酸性度をもたないC(sp3)-H結合の含有量が最も多い。
今回開発した、飽和複素環に対するベンゾアゾールユニットの1工程導入法は、従来法では変換が困難な酸性度をもたないC(sp3)-H結合を官能基化できる新たな手法である。本手法がさらに進展すれば、現存医薬品などに対して、さらなる官能基化や構造複雑化が実現でき、分子構造変換を伴う機能増強や新機能の獲得が期待できる。