Abstract
Ruthenium-catalyzed formation of pyrazoles or 3-hydroxynitriles from propargyl alcohols and hydrazines
Highlights
We discovered that bifunctional ruthenium cyclopentadienone complexes such as catalyst 1 and derivatives thereof bring about various selective transformations of propargyl alcohols with diverse nucleophiles
The ruthenium-catalyzed conversion of secondary propargyl alcohols 2a-j with hydrazine hydrate led to the formation of various pyrazoles 3
No conversion of the propargyl alcohols is observed in absence of the ruthenium catalyst
Summary
The pyrazole nucleus represents a pharmacologically privileged substructure that occurs in numerous pharmaceutical and agrochemical agents.[1,2,3] Various types of pharmacological properties, such as antibacterial, antifungal, anticancer, antidepressant, antiinflammatory, anti-tuberculosis, antioxidant as well as antiviral activity have been described for pyrazole derivatives.[1,2] a variety of efficient and versatile synthetic methods have been developed to assemble this structural motif.[2,3,4,5,6,7,8,9,10,11] The 1,3-dipolar cycloaddition of diazoalkanes or nitrile imines with olefins and alkynes is limited in terms of the accessibility of the 1,3dipoles.[2,3,4] The more frequently applied classical cyclocondensation of hydrazines with 1,3-dicarbonyl compounds (Knorr synthesis) or acetylenic ketones provides a rapid approach to obtain substituted pyrazoles.[2,3,4,5,6,7] Alternatively, the more readily available enones can be used, but this requires an additional oxidation step.[2,3,4,8,9,10,11] In this context, ruthenium catalysis is often utilized and various modes of oxidative catalytic activity are applied, including oxidative C-N coupling,[9] hydrogen transfer,[10] and visible light photoredox catalysis.[11]. Secondary propargyl alcohols are converted in a redox-isomerization / Michael addition cascade.[12,13,14,15,16] Saturated tertiary substrates generate diverse addition or substitution products,[13,15,20] whereas tertiary 1-alkenyl propargyl alcohols undergo an allylation/cycloisomerization cascade process.[13,14,16,17,18,19,20] we report on a mechanistically related formation of pyrazoles from secondary propargyl alcohols and hydrazines as well as the generation of 3-hydroxynitriles from tertiary substrates applying similar reaction conditions (Scheme 1). The ruthenium-catalyzed conversion of secondary propargyl alcohols 2a-j with hydrazine hydrate led to the formation of various pyrazoles 3. Alkyl-substituted substrates 2a and 2f led to small amounts of 3-hydroxynitriles 4 as byproducts, whereas the hydroamination side product (5) is formed solely from the sterically simplest derivative 2a.
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