Pyrazole Synthesis Using a Titanium‐Catalyzed Multicomponent Coupling Reaction and Synthesis of Withasomnine

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.