γ-Hydroxyalkynyl Ketones as Useful Scaffolds for the Preparation of Combinatorial Libraries of Furans, Isoxazoles and Pyrazoles

Abstract

Using 5-hydroxy-hex-3-yne-2-one (9) as a model substrate, the utility of the gamma-hydroxyl alkynyl ketone scaffold for the preparation of combinatorial libraries of furans, isoxazoles, and pyrazoles is described. The addition of hydrazoic acid to the acetylenic ketone 9 forms in a single step both 3-azido-2,5-dimethyl furan (10) and alpha,5-dimethyl-3-isoxazolemethanol (11). Reaction of a mixture of (E)- and (Z)-bromoenediones (5 and 6), accessible from 3-bromo-2,5-dimethyl furan (17), with 1,1-dimethylhydrazine afforded a nearly quantitative yield of 1,3-dimethyl-5-acetylpyrazole (18). When the (E)- and (Z)-vinyl bromides 5 and 6 were reacted with sodium azide, 3-acetyl-5-methylisoxazole (7) formed via the intermediate (Z)-3-azido-3-hexene-2,5-dione (4), was the only product.

The Boulton–Katritzky rearrangement of isocarboxazid

“…There is increased interest in monoamine oxidase inhibitors [24] and the crystal structures of monoamine oxidase A [25] and monoamine oxidase B [26] as well as the crystal structure of isocarboxazid (1) [27] have been solved. Combinatorial routes to 3-acylisoxazoles have been described [12,28]. The unmasking of a ketone functionality in this pericyclic rearrangement may have biochemical implications.…”

Photochromic and fluorescent properties of bisfurylethene derivatives

“…The crude product was purified by column chromatography on silica gel (hexane) to give 0.224 g of 1a in 28% yield as colorless crystals; mp. 116-117 uC; To a stirred THF solution (30 ml) containing 3-bromo-2,5dimethyl-5-phenylfuran (3) 27 (3.6 g, 20.6 mmol) was slowly added 14.1 ml of 1.6 M butyllithium hexane solution (22.6 mmol) at 278 uC, and the solution was stirred for 15 min at 278 uC. Then octafluorocyclopentene (1.36 ml, 10.3 mmol) was added slowly to the reaction mixture at 278 uC, and left to stand with stirring at 278 uC to 30 uC for 12 h. The reaction mixture was poured into concentrated sodium ammonium chloride solution and extracted with diethyl ether.…”

Electrophilic Cyclizations of 2‐Fluoroalk‐3‐yn‐1‐ones: Room‐Temperature Synthesis of Diversely 2,5‐Disubstituted 3,4‐Fluorohalofurans

“…In particular, iodo-and bromofurans are useful substrates for a variety bond-forming reactions, [5,6] and also serve as building blocks for combinatorial chemistry. [7] Pharmaceutical components containing fluorine have found a wide application in medicinal chemistry.…”