Gold-catalyzed three-component spirocyclization: a one-pot approach to functionalized pyrazolidines

Abstract

An efficient, highly atom economic synthesis of hitherto unknown spirocyclic pyrazolidines in a one-pot process was developed. The gold-catalyzed three-component coupling of alkynols, hydrazines and aldehydes or ketones likely proceeds via cycloisomerization of the alkynol to an exocyclic enol ether and subsequent [3 + 2]-cycloaddition of an azomethine ylide. A library of 29 derivatives with a wide range of functional groups was synthesized in up to 97% yield. With this new method, every position in the final product can be substituted which renders the method ideal for applications in combinatorial or medicinal chemistry.

Acid- and Au(i)-mediated synthesis of hexathymidine-DNA-heterocycle chimeras, an efficient entry to DNA-encoded libraries inspired by drug structures

“…In line with our hypothesis, we describe here the synthesis of hexT -conjugates of diverse substituted β-carbolines by the Brønsted acid-catalyzed Pictet–Spengler reaction, 16 and the synthesis of hexT -conjugates of highly substituted pyrazol(in)es by a Au( i )-mediated cascade reaction 17 a from simple, readily available starting materials. These scaffolds can be found in numerous bioactive compounds, among them natural products and drugs (Fig.…”

An Efficient Protocol for the Production of Pymetrozine via a New Synthetic Strategy

“…In the process to prepare 3, following the literature [16][17][18] , dimethyl carbonate (1.05 equiv.) and 80% hydrazine hydrate (1 equiv.)…”

Allylation of isatin-derived N-Boc-hydrazones followed by Pd-catalyzed carboamination reaction: an entry to 3-spiro-pyrazolidyl-oxindoles

“…19 At the best of our knowledge, only a recent work describes spirocyclic pyrazolidines, achieved by means of a gold-catalyzed three-component spirocyclization, starting from alkynols, hydrazines and carbonyl components, mainly aldehydes. 20 No methods have been reported for the preparation of pyrazolidines derived from cyclic ketones and, of course, of oxindoles bearing an N-jointed pyrazolidine ring at the key C3 position.…”