Synthesis 2018; 50(03): 514-528
DOI: 10.1055/s-0036-1591728
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© Georg Thieme Verlag Stuttgart · New York

Regioselective Syntheses of Fluorinated Cyclopentanone Derivatives: Ring Construction Strategy Using Transition-Metal–Difluorocarbene Complexes and Free Difluorocarbene

Kohei Fuchibe
a  Division of Chemistry, Faculty of Pure and Applied Sciences, University of Tsukuba, Tsukuba, Ibaraki 305–8571, Japan   Email: junji@chem.tsukuba.ac.jp
,
Ryo Takayama
a  Division of Chemistry, Faculty of Pure and Applied Sciences, University of Tsukuba, Tsukuba, Ibaraki 305–8571, Japan   Email: junji@chem.tsukuba.ac.jp
,
Tatsuya Aono
a  Division of Chemistry, Faculty of Pure and Applied Sciences, University of Tsukuba, Tsukuba, Ibaraki 305–8571, Japan   Email: junji@chem.tsukuba.ac.jp
,
Ji Hu
a  Division of Chemistry, Faculty of Pure and Applied Sciences, University of Tsukuba, Tsukuba, Ibaraki 305–8571, Japan   Email: junji@chem.tsukuba.ac.jp
,
Tomohiro Hidano
a  Division of Chemistry, Faculty of Pure and Applied Sciences, University of Tsukuba, Tsukuba, Ibaraki 305–8571, Japan   Email: junji@chem.tsukuba.ac.jp
,
Hisashi Sasagawa
a  Division of Chemistry, Faculty of Pure and Applied Sciences, University of Tsukuba, Tsukuba, Ibaraki 305–8571, Japan   Email: junji@chem.tsukuba.ac.jp
,
Masaki Fujiwara
b  Department of Applied Chemistry, Kyushu Institute of Technology, Kitakyushu, Fukuoka 804–8550, Japan
,
Shinji Miyazaki
b  Department of Applied Chemistry, Kyushu Institute of Technology, Kitakyushu, Fukuoka 804–8550, Japan
,
Ryo Nadano
c  Department of Chemistry, Graduate School of Science, The University of Tokyo, Hongo, Bunkyo-ku, Tokyo 113–0033, Japan
,
a  Division of Chemistry, Faculty of Pure and Applied Sciences, University of Tsukuba, Tsukuba, Ibaraki 305–8571, Japan   Email: junji@chem.tsukuba.ac.jp
› Author Affiliations
This work was supported by JSPS KAKENHI Grant Numbers JP16H01002 (J.I.), JP16K13943 (J.I.), JP15K05414 (K.F.).
Further Information

Publication History

Received: 18 October 2017

Accepted: 26 October 2017

Publication Date:
11 December 2017 (online)


Abstract

The syntheses of fluorinated cyclopentanone derivatives, which have pharmaceutical and agrochemical importance are reported. The catalytic reaction of copper(I) and nickel(II) difluorocarbenes with silyl dienol ethers afforded 4,4-difluoro- and 5,5-difluorocyclopent-1-en-1-yl silyl ethers, respectively. The fluorine-directed and -activated Nazarov cyclization of 1-fluorovinyl vinyl ketones, which were prepared from silyl dienol ethers and free difluorocarbene, proceeded efficiently to afford 2-fluorocyclopent-2-en-1-ones. Moreover, fluorine-­directed Nazarov cyclizations of 2,2-difluorovinyl vinyl ketones and 1-(trifluoromethyl)vinyl vinyl ketones afforded 3-fluorocyclopent-2-en-1-ones and 5-(trifluoromethyl)cyclopent-2-en-1-ones, respectively. In addition, derivatization of ring-difluorinated products also provided 3-fluorocyclopent-2-en-1-ones.

Supporting Information

 
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