One‐Pot Synthesis of Pyrazoles through a Four‐Step Cascade Sequence

Abstract

A one-pot synthesis of 3,4,5- and 1,3,5-pyrazoles from tertiary propargylic alcohols and para-tolylsulfonohydrazide has been accomplished. The pyrazoles are formed through a four-step cascade sequence, including FeCl3 -catalyzed propargylic substitution, aza-Meyer-Schuster rearrangement, base-mediated 6π electrocyclization, and thermal [1,5] sigmatropic shift. In this reaction, the 3,4,5- and 1,3,5-pyrazoles are produced selectively according to different substituents in the starting alcohols.

Iron Catalysis in Organic Synthesis

“…124 This outcome is explained by the fact that elimination of TsNHTMS leading to the cyanation cannot occur in this situation. Instead, p-toluenesulfinic acid is eliminated and the resulting diazo compound cyclizes to the pyrazole followed by a [1,5]-sigmatropic aryl shift.…”

Recent Developments in the Meyer‐Schuster Rearrangement

“…Short time later, the same authors developed a synthesis of pyrazoles based on similar starting materials 285 (Scheme 71). [126] The difference was that, immediately after the aza ‐MSR, they heated the reaction mixture with a base. Extensive screening showed that Cs 2 CO 3 , and also K 2 CO 3 , were the most efficient bases.…”

Iron(III) Chloride Catalyzed Nucleophilic Substitution of Tertiary Propargylic Alcohols and Synthesis of Iodo-3H-Pyrazoles

“…7 We have also developed a one-pot synthesis of pyrazoles from the same starting materials through a four-step cascade sequence (Scheme 1, d). 8 More recently, Chen and co-workers reported the Y(OTf) 3 -catalyzed stereoselective synthesis of α,βunsaturated hydrazones from tertiary propargylic alcohols and p-toluenesulfonyl hydrazide (Scheme 1, b). 9 As part of our ongoing efforts to expand the synthetic utility of tertiary propargylic hydrazides, we report a highly efficient FeCl 3 -catalyzed substitution of tertiary propargylic alcohols to give propargylic hydrazides, and the synthesis of iodo-3H-pyrazoles (Scheme 1, e).…”