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Pyrazole Synthesis Using a Titanium‐Catalyzed Multicomponent Coupling Reaction and Synthesis of Withasomnine
Author(s) -
Majumder Supriyo,
Gipson Kevin R.,
Staples Richard J.,
Odom Aaron L.
Publication year - 2009
Publication title -
advanced synthesis and catalysis
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.541
H-Index - 155
eISSN - 1615-4169
pISSN - 1615-4150
DOI - 10.1002/adsc.200900293
Subject(s) - regioselectivity , chemistry , alkyne , catalysis , hydrazine (antidepressant) , pyrazole , tautomer , yield (engineering) , titanium , combinatorial chemistry , coupling reaction , organic chemistry , amine gas treating , materials science , chromatography , metallurgy
The titanium‐catalyzed 3‐component coupling of an alkyne, isonitrile, and amine can be used to generate tautomers of 1,3‐diimines. These diimines produced in situ undergo cyclization with hydrazine and hydrazine derivatives in a one‐pot procedure to provide pyrazoles. Seventeen examples of pyrazoles are provided using this one‐pot, 4‐component procedure from simple starting materials. The regioselectivity of the alkyne addition can be controlled in some cases with catalyst architecture, and regioselectivity of monosubsituted hydrazines to unsymmetrical 1,3‐diimines is discussed. This multicomponent coupling strategy was applied to the synthesis of withasomnine in an efficient procedure, which gave the natural product in 24% overall yield from 4‐pentyn‐1‐ol.