α-Functionally Substituted α,β-Unsaturated Aldehydes as Fine Chemicals Reagents: Synthesis and Application

α-Functionalized α,β-unsaturated aldehydes is an important class of compounds, which are widely used in fine organic synthesis, biology, medicine and pharmacology, chemical industry, and agriculture. Some of the 2-substituted 2-alkenals are found to be the key metabolites in plant and animal cells. Therefore, the development of efficient methods for their synthesis attracts the attention of organic chemists. This review focusses on the recent advances in the synthesis of 2-functionally substituted 2-alkenals. The approaches to the preparation of α-alkyl α,β-unsaturated aldehydes are not included in this review.     

Microwave-initiated hydroamination of 2-ethoxypropenal with secondary amines

Reactions of 2-ethoxyprop-2-enal with cycloaliphatic secondary amines (morpholine, piperidine, pyrrolidine) follow 1,4- or 1,2-addition pattern with subsequent condensation of the adduct with the initial amine to produce isomeric 2-ethoxyprop-2-ene-1,1-diamines and 2-ethoxyprop-1-ene-1,3-diamines. These reactions are accelerated by a factor of 15–30 under microwave irradiation and in the presence of water. The regioselectivity of primary nucleophilic attack varies over a wide range, depending on the amine basicity and reactant ratio. The reaction of 2-ethoxyprop-2-enal with pyrrolidine and water at a ratio of 1: 10: 10 was characterized by increased regioselectivity of 1,4-addition (up to 75%). Unlike cycloaliphatic amines, 2-ethoxyprop-2-enal reacted with N-methylaniline under microwave irradiation at a lower rate to give 2-ethoxy-N ¹,N ¹,N ³-trimethyl-N ¹,N ¹,N ³-triphenylpropane-1,1,3-triamine.     

Synthesis of oxazolines and oxazoles by the reaction of propynals with tosylmethyl isocyanide

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One-pot,three-component cascade synthesis of new tetrasubstituted pyrroles by coupling reaction of 2-functionally substituted 2-alkenals,amines, and nitroethane

The reactivity of 2-alkylthio(2-alkoxy)-substituted 3-aryl(hetaryl)propenals in a one-pot, three-component reaction with primary amines and nitroethane has been studied. A method for the synthesis of highly functionalized pyrroles (in 36–80% yield) from 2-alkylthiopropenals has been developed on the basis of this reaction. It is found that the reaction proceeds via formation of the intermediate imine of the starting enal, which undergoes 1,2-addition by nitroethane to give kinetically controlled 2-alkylthio-3-alkylamino-1-aryl(hetaryl)-4-nitropentene. When left to stand, upon heating or under microwave assistance, this adduct can be transformed into the thermodynamically controlled 1,4-adduct. The latter undergoes intramolecular cyclization to afford the target pyrrole. A possibility of such isomerization of addition products of nitroalkane to 2-functionalized α,β-unsaturated imines is revealed for the first time. Scope of the reaction depending upon its conditions as well as structure of the starting substrates and amines has been studied.     

Syntheses of quinolines and their derivatives from α,β-unsaturated aldehydes

Chemistry of Heterocyclic Compounds - The methods for the synthesis of quinoline and its hydrogenated derivatives from α,β-unsaturated aldehydes have been summarized for the first time....