Gold/Acid‐Co‐catalyzed Direct Microwave‐Assisted Synthesis of Fused Azaheterocycles from Propargylic Hydroperoxides

Abstract

The gold-acid-co-catalyzed synthesis of nine series of fused azaheterocycles with structural diversity starting from the same synthons as readily available propargylic hydroperoxides and aromatic amines has been achieved. The overall tandem process consists in a gold-catalyzed hydroperoxide rearrangement/Michael reaction followed by a final acid-catalyzed cyclization.

Safe and Fast Flow Synthesis of Functionalized Oxazoles with Molecular Oxygen in a Microstructured Reactor

“…By applying mild conditions with gold­(I) catalysis, generating alkylideneoxazolines, and in situ converting it with molecular oxygen, the oxazole core is built up and immediately functionalized to efficiently form hydroperoxymethyl oxazoles in an atom-economic and green process . The hydroperoxymethyl group offers potential for multifunctional conversions by reduction, rearrangements, or follow-up reactions . Contrary to other methods that use, e.g., hypervalent iodine reagents or pyridine/quinoline N -oxides as oxidizing agents in the formation of oxazoles, the direct oxidation with molecular oxygen and introduction of a versatile functionality in one step is very convenient and conforms to the pursuit of atom economy.…”

“…10 The hydroperoxymethyl group offers potential for multifunctional conversions by reduction, 11 rearrangements 12 or follow-up reactions. 13 Contrary to other methods that use, e.g., hypervalent iodine reagents 14 or pyridine/quinoline N-oxides 15 as oxidizing agents in the formation of oxazoles, the direct oxidation with molecular oxygen and introduction of a versatile functionality in one step is very convenient and conforms to the pursuit of atom economy. Molecular oxygen was used in combination with high temperatures and very polar solvents to oxidize oxazolines to oxazoles 16 or in a copper-catalyzed [2+2+1] cycloaddition 17 without generating an additional functional group.…”

Synthesis of 7-arylethyl-5-arylpyrazolo $$[1{,}5\hbox {-}a]$$ [ 1 , 5 - a ] pyrimidines through an aza-Michael addition/nucleophilic addition/1,3-hydrogen transfer cascade

“…The recently reported methods for the synthesis of pyrazolo [1,5-a]pyrimidines include i) gold-acid-cocatalyzed reactions of propargylic hydroperoxides with 3-aminopyrazole; 12 ii) the base induced reactions of 1,3,5-trisubstituted pentane-1,5-diones with substituted pyrazoles; 13 iii) the base catalyzed reactions of chalcones with 3-aminopyrazoles; 14 iv) the reactions of 1,2-allenic ketones with 3-aminopyrazoles; 15 v) the concentrated hydrochloric acid catalyzed condensation of 1,3-diketones with substituted aminopyrazoles; 16 vi) the hydrotalcite catalyzed reactions of enaminones with aminopyrazole derivatives; 17 and vii) the condensation of 2-pyrone with 3-amino-5-arylpyrazoles. 18 However, commercially unavailable reagents, harsh reaction conditions, and regioselectivity concerns restricted their use in regular processes.…”

CuI‐Catalyzed Synthesis of Propargyl Hydroperoxides Using Molec­ular Oxygen and Hydroxylamines

“…Here, we report the Cu I ‐catalyzed oxidation of enynes using molecular oxygen with either NHPI or HOBt to yield propargyl hydroperoxides (Scheme ). These peroxides have emerged as synthetically useful substrates because they serve as precursors to β‐functionalized ketones21 and fused heterocycles 22. Under reductive or basic conditions, propargyl peroxides can be converted into propargyl alcohols and ketones, respectively 23.…”

“…Under reductive or basic conditions, propargyl peroxides can be converted into propargyl alcohols and ketones, respectively 23. The synthesis of propargyl peroxides using oxygen is rare,24 often requiring the use of low‐molecular‐weight peroxides such as hydrogen peroxide21,22,25 or tert ‐butyl hydroperoxide,23 which are potentially explosive 26…”