Thermally Controlled Decarboxylative [4 + 2] Cycloaddition between Alkoxyoxazoles and Acrylic Acid: Expedient Access to 3-Hydroxypyridines

Abstract

A modified Kondrat'eva cycloaddition involving an unprecedented thermally controlled metal-free decarboxylative aromatization affords an expedient access to natural 3-hydroxypyridine/piperidine systems.

Regioselective Solid‐Phase Synthesis of Peptide Analogues Containing 3,4‐ or 3,5‐Disubstituted Isoxazole as s‐cis or s‐trans Peptide Bond Mimics

“…and 4‐dimethylaminopyridine (0.3 equiv.) were added in CH 2 Cl 2 /NMP (6 mL, 3:2 v/v) at room temperature overnight, as described previously, and the resin was washed with DCM (3 × 5 mL), DMF (3 × 5 mL) and MeOH (5 × 5 mL). The cycloaddition reaction was then performed after addition of the Fmoc‐amino chloroxime (1 equiv.)…”

PdCl2/CuCl2/Bi(OTf)3‐promoted Construction of Sulfonyl Dibenzooxabicyclo[3.3.1]nonanes and Arylnaphthalenes via Intramolecular Annulation of Sulfonyl o‐Allylarylchromanones

“…Among these diverse kinds of reaction routes, a number of synthetic efforts have attempted to control one factor or variant to generate different products with approximate or distinct skeletons in recent reports. These adjusting factors included temperature, [1–14] catalyst, [15–21] additive (e. g. ligand, [22–25] base [26–27] and reagent [28–31] ) and solvent [32–35] . On the basis of the abovementioned investigations, we found that controlling the temperature change is a simple, economical and direct protocol for affecting the formation of different products in comparison with other variables.…”

5‐Alkoxyoxazole – A Versatile Building Block in (Bio)organic Synthesis

“…Further optimization of the cycloaddition step enabled direct access to 4‐ and 5‐unsubstituted 3‐hydroxypyridines 42 from 5‐alkoxyoxazole precursors 1 under milder conditions than those used for methyl multijuguinate (150 vs. 250 °C, CH 3 CN vs. NMP, catalyst‐free) . The synthetic method proved general and wide in scope (26 examples, 23–79 % yield).…”

“…Naturally occurring 2,6‐disubstituted 3‐hydroxypyridines have been prepared by using this decarboxylative Kondrat'eva reaction. Methyl multijuguinate was prepared within three steps in 35 % overall yield (Scheme ) . Moreover, the pyridine derivatives prepared by this method can be used as key intermediates for the synthesis of naturally occurring piperidinols (e.g., azimic acid and deoxocassine) and fused piperidinol systems (e.g., indolizidine).…”