New preparation and synthetic reactions of 3,3,3-trifluoropropynyllithium, -borate and -stannane: Facile synthesis of trifluoromethylated allenes, arylacetylenes and enynes

Masaki Shimizu, Masahiro Higashi, Youhei Takeda, Masahito Murai, Guofang Jiang, Yuiga Asai, Yoshiaki Nakao, Eiji Shirakawa, Tamejiro Hiyama

Research output: Contribution to journalArticle

14 Citations (Scopus)

Abstract

Background: Since trifluoromethyl-containing compounds have found diverse applications in the fields of pharmaceuticals and agrochemicals, facile and selective synthetic methods for trifluoromethyl-substituted compounds are an essential tool for advanced medicinal chemistry. Now that diverse synthetic transformations of carbon-carbon triple bonds are available, 3,3,3-trifluoropropynyl-substituted compounds serve as versatile building blocks for target molecules containing trifluoromethyl groups. Thus, novel synthetic methods and reagents for incorporation of a 3,3,3-trifluoropropynyl group into an organic compound have been the major concern in exploration and modification of fluorine-based biologically active substances. Results & discussion: We report a preparative method of 3,3,3-trifluoropropynyllithium and its reaction with electrophiles including aldehydes, ketones, trimethoxyborane, chlorosilanes and chlorostannanes in detail. Palladium-catalyzed synthetic reactions of the carbonyl adducts and the trifluoromethyl-containing metalloid reagents are also demonstrated, which provide simple synthetic methods of trifluoromethylated allenes, arylacetylenes and enynes. The synthetic transformations presented here expand the repertoire of trifluoromethylated compounds available for medicinal scientists and contribute to the advance of future medicinal chemistry.

Original languageEnglish
Pages (from-to)921-945
Number of pages25
JournalFuture Medicinal Chemistry
Volume1
Issue number5
DOIs
Publication statusPublished - Aug 2009
Externally publishedYes

Fingerprint

Borates
Pharmaceutical Chemistry
Carbon
Metalloids
Agrochemicals
Fluorine
Palladium
Ketones
Aldehydes
stannane
propadiene
Pharmaceutical Preparations

ASJC Scopus subject areas

  • Drug Discovery
  • Pharmacology
  • Molecular Medicine

Cite this

New preparation and synthetic reactions of 3,3,3-trifluoropropynyllithium, -borate and -stannane : Facile synthesis of trifluoromethylated allenes, arylacetylenes and enynes. / Shimizu, Masaki; Higashi, Masahiro; Takeda, Youhei; Murai, Masahito; Jiang, Guofang; Asai, Yuiga; Nakao, Yoshiaki; Shirakawa, Eiji; Hiyama, Tamejiro.

In: Future Medicinal Chemistry, Vol. 1, No. 5, 08.2009, p. 921-945.

Research output: Contribution to journalArticle

Shimizu, Masaki ; Higashi, Masahiro ; Takeda, Youhei ; Murai, Masahito ; Jiang, Guofang ; Asai, Yuiga ; Nakao, Yoshiaki ; Shirakawa, Eiji ; Hiyama, Tamejiro. / New preparation and synthetic reactions of 3,3,3-trifluoropropynyllithium, -borate and -stannane : Facile synthesis of trifluoromethylated allenes, arylacetylenes and enynes. In: Future Medicinal Chemistry. 2009 ; Vol. 1, No. 5. pp. 921-945.
@article{d35e6bd2f7894136b28a994708e73111,
title = "New preparation and synthetic reactions of 3,3,3-trifluoropropynyllithium, -borate and -stannane: Facile synthesis of trifluoromethylated allenes, arylacetylenes and enynes",
abstract = "Background: Since trifluoromethyl-containing compounds have found diverse applications in the fields of pharmaceuticals and agrochemicals, facile and selective synthetic methods for trifluoromethyl-substituted compounds are an essential tool for advanced medicinal chemistry. Now that diverse synthetic transformations of carbon-carbon triple bonds are available, 3,3,3-trifluoropropynyl-substituted compounds serve as versatile building blocks for target molecules containing trifluoromethyl groups. Thus, novel synthetic methods and reagents for incorporation of a 3,3,3-trifluoropropynyl group into an organic compound have been the major concern in exploration and modification of fluorine-based biologically active substances. Results & discussion: We report a preparative method of 3,3,3-trifluoropropynyllithium and its reaction with electrophiles including aldehydes, ketones, trimethoxyborane, chlorosilanes and chlorostannanes in detail. Palladium-catalyzed synthetic reactions of the carbonyl adducts and the trifluoromethyl-containing metalloid reagents are also demonstrated, which provide simple synthetic methods of trifluoromethylated allenes, arylacetylenes and enynes. The synthetic transformations presented here expand the repertoire of trifluoromethylated compounds available for medicinal scientists and contribute to the advance of future medicinal chemistry.",
author = "Masaki Shimizu and Masahiro Higashi and Youhei Takeda and Masahito Murai and Guofang Jiang and Yuiga Asai and Yoshiaki Nakao and Eiji Shirakawa and Tamejiro Hiyama",
year = "2009",
month = "8",
doi = "10.4155/fmc.09.69",
language = "English",
volume = "1",
pages = "921--945",
journal = "Future Medicinal Chemistry",
issn = "1756-8919",
publisher = "Future Science",
number = "5",

}

TY - JOUR

T1 - New preparation and synthetic reactions of 3,3,3-trifluoropropynyllithium, -borate and -stannane

T2 - Facile synthesis of trifluoromethylated allenes, arylacetylenes and enynes

AU - Shimizu, Masaki

AU - Higashi, Masahiro

AU - Takeda, Youhei

AU - Murai, Masahito

AU - Jiang, Guofang

AU - Asai, Yuiga

AU - Nakao, Yoshiaki

AU - Shirakawa, Eiji

AU - Hiyama, Tamejiro

PY - 2009/8

Y1 - 2009/8

N2 - Background: Since trifluoromethyl-containing compounds have found diverse applications in the fields of pharmaceuticals and agrochemicals, facile and selective synthetic methods for trifluoromethyl-substituted compounds are an essential tool for advanced medicinal chemistry. Now that diverse synthetic transformations of carbon-carbon triple bonds are available, 3,3,3-trifluoropropynyl-substituted compounds serve as versatile building blocks for target molecules containing trifluoromethyl groups. Thus, novel synthetic methods and reagents for incorporation of a 3,3,3-trifluoropropynyl group into an organic compound have been the major concern in exploration and modification of fluorine-based biologically active substances. Results & discussion: We report a preparative method of 3,3,3-trifluoropropynyllithium and its reaction with electrophiles including aldehydes, ketones, trimethoxyborane, chlorosilanes and chlorostannanes in detail. Palladium-catalyzed synthetic reactions of the carbonyl adducts and the trifluoromethyl-containing metalloid reagents are also demonstrated, which provide simple synthetic methods of trifluoromethylated allenes, arylacetylenes and enynes. The synthetic transformations presented here expand the repertoire of trifluoromethylated compounds available for medicinal scientists and contribute to the advance of future medicinal chemistry.

AB - Background: Since trifluoromethyl-containing compounds have found diverse applications in the fields of pharmaceuticals and agrochemicals, facile and selective synthetic methods for trifluoromethyl-substituted compounds are an essential tool for advanced medicinal chemistry. Now that diverse synthetic transformations of carbon-carbon triple bonds are available, 3,3,3-trifluoropropynyl-substituted compounds serve as versatile building blocks for target molecules containing trifluoromethyl groups. Thus, novel synthetic methods and reagents for incorporation of a 3,3,3-trifluoropropynyl group into an organic compound have been the major concern in exploration and modification of fluorine-based biologically active substances. Results & discussion: We report a preparative method of 3,3,3-trifluoropropynyllithium and its reaction with electrophiles including aldehydes, ketones, trimethoxyborane, chlorosilanes and chlorostannanes in detail. Palladium-catalyzed synthetic reactions of the carbonyl adducts and the trifluoromethyl-containing metalloid reagents are also demonstrated, which provide simple synthetic methods of trifluoromethylated allenes, arylacetylenes and enynes. The synthetic transformations presented here expand the repertoire of trifluoromethylated compounds available for medicinal scientists and contribute to the advance of future medicinal chemistry.

UR - http://www.scopus.com/inward/record.url?scp=77952842013&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=77952842013&partnerID=8YFLogxK

U2 - 10.4155/fmc.09.69

DO - 10.4155/fmc.09.69

M3 - Article

C2 - 21426090

AN - SCOPUS:77952842013

VL - 1

SP - 921

EP - 945

JO - Future Medicinal Chemistry

JF - Future Medicinal Chemistry

SN - 1756-8919

IS - 5

ER -