Ruthenium-catalyzed formation of pyrazoles or 3-hydroxynitriles from propargyl alcohols and hydrazines

Abstract

Functionalized pyrazoles are generated from secondary propragyl alcohols and hydrazines in a rutheniumcatalyzed cascade process, consisting of redox isomerization, Michael addition, cyclocondensation and dehydrogenation steps. The same bifunctional catalyst mediates the conversion of tertiary propargyl alcohols with hydrazine to 3-hydroxynitriles via anti-Markovnikov hydroamination followed by elimination of ammonia.

Phosphine-Free Ruthenium Complex-Catalyzed Synthesis of Mono- or Dialkylated Acyl Hydrazides via the Borrowing Hydrogen Strategy

“…However, the introduction of ruthenium analogues in this hydrogen-borrowing strategy opened the way to the synthesis of alkylated hydrazide compounds. The complex Ru1 , bearing the electron-rich cyclopentadienone ligand, has been initially developed and applied by Haak for the activation of propargyl alcohol . The ruthenium complexes Ru1 – 3 were activated either by addition of Me 3 NO ( Ru1 and Ru3 ) or thermally ( Ru2 ), the Shvo’s complex ( Ru4 ) was used without any further activation.…”

Synthetic Strategies and Biological Activities of 1,5-Disubstituted Pyrazoles and 2,5-Disubstituted Thiazoles

“…Metal catalysts have proved to be quite efficient in organic chemistry as means of carrying out various and sometimes difficult transformations. In the synthesis of pyrazoles, the bifunctional ruthenium cyclopentadienone complex (Ru Catalyst) catalyzes the reaction between secondary propargyl alcohols and nucleophiles such as hydrazine giving 1,5-disubstituted pyrazoles along with byproducts [3]. This cascade conversion likely proceeds via cycloisomerization, Michael addition, cyclocondensation and dehydrogenation/oxidation) steps [3].…”

“…In the synthesis of pyrazoles, the bifunctional ruthenium cyclopentadienone complex (Ru Catalyst) catalyzes the reaction between secondary propargyl alcohols and nucleophiles such as hydrazine giving 1,5-disubstituted pyrazoles along with byproducts [3]. This cascade conversion likely proceeds via cycloisomerization, Michael addition, cyclocondensation and dehydrogenation/oxidation) steps [3]. The reaction proceeds via microwave irradiation in toluene and when the nucleophile is phenyl hydrazine (2), both the 1,5-and 1,3-disubstituted regioisomers (a and b) are formed along with the 3-phenylbutene byproduct c (Figure 4) [3].…”

“…This cascade conversion likely proceeds via cycloisomerization, Michael addition, cyclocondensation and dehydrogenation/oxidation) steps [3]. The reaction proceeds via microwave irradiation in toluene and when the nucleophile is phenyl hydrazine (2), both the 1,5-and 1,3-disubstituted regioisomers (a and b) are formed along with the 3-phenylbutene byproduct c (Figure 4) [3]. The trends in the yields indicates that when the R group of the propargyl alcohol 1 is bulky or has unsaturated side chains, the reaction favors the 1,5-disubstituted pyrazoles leading to higher yield of this regioisomer.…”

“…From a mechanistic perspective as shown in Figure 5, Kaufmann et al [3] reported that the propargyl alcohol is activated by the Ru catalyst to form the by the chelated π-complex I, which is then converted to the alkynyl species II. A 1,2-hydrogen shift forms the alkenyl complex III which then undergoes a regioselective nucleophilic attack by phenyl hydrazine to give complex IV.…”