Alkylation at the -carbon of ethyl acetoacetate via an alkali metal enolate and subsequent removal of the ester group by sequential hydrolysis and decarboxylation provides a classical synthesis of methyl ketones (eq 1). The ambident reactivity of the acetoacetate anion often causes competing - and -alkylations. The extent of vs.
-acylation at the -carbon of ethyl acetoacetate may be achieved by reaction of the magnesio or sodio derivative with an acid chloride. Acylation may also be performed efficiently in the presence of MgCl and pyridine (eq 9).The dianions of acetoacetates undergo --acylation with esters. Proton transfer occurs readily from product to the starting enolate.
Ethyl Acetoacetate: 10.0 mL (1.029g/mL) ..
The Robinson annulation is a three-step process involving a Michael addition followed by an internal aldol condensation and a dehydration. Under appropriate experimental conditions, it is possible to stop the reaction after every step and to isolate the three products separately. This feature is particularly attractive in the frame of an organic chemistry course. It allows students to confirm experimentally the validity of the stepwise mechanism and to obtain a more thorough understanding of the whole process. It also permits them to synthesize a rich set of related molecules that can be compared and characterized through various analytical techniques. Thus, a stoichiometric mixture of chalcone and ethyl acetoacetate was reacted in ethanol. Depending on the quantity of barium hydroxide monohydrate used as catalyst, the reaction time, and the temperature, three different products were obtained. Their full IR, 1H, 13C, COSY, NOESY, and HETCOR NMR spectra are supplied. Examination of the spectroscopic data helps uncover many challenging structural analysis problems. Among them, the diastereoselective formation of chiral centers during the annulation process, the distinction between axial and equatorial substituents on a cyclohexane ring, and the possibility of a keto–enol tautomerism are extensively discussed.
vinyl azides and ethyl acetoacetate through the 1,4 ..
Highly enantioselective asymmetric hydrogenation of acetoacetates can be achieved using -ruthenium complexes (eq 21). The resulting 3-hydroxybutanoates (see ) are versatile auxiliaries and building blocks for the synthesis of enantiomerically pure products.
Knorr pyrrole synthesis - Wikipedia
In such cases, alkylation may be achieved via reaction of the enol with cationic species (eq 3).Metal coordinated alkenes react with acetoacetate anion, affording an alternative type of alkylation. -Allyl palladium species, catalytically generated by reaction of Pd0 complexes with allylic acetates or halides, provide efficient -allylation of the acetoacetate anion. Alkylations with vinyl epoxides, allylic carbonates, and allylic carbamates via Pd0 catalysis proceed without the need for an external base since the -allylpalladium species in these systems are sufficiently basic to deprotonate acetoacetate in situ. The regio- and stereoselectivities in alkylations with cyclic vinyl epoxides (eq 4) are opposite to those observed under standard carbanion conditions. A highly efficient Pd0-catalyzed addition of methyl acetoacetate to 1,3-dienes can be achieved using ligand (eq 5). promotes the radical addition of ethyl acetoacetate to enol ethers and subsequent oxidative cyclization to 1-alkoxy-1,2-dihydrofurans, which may be hydrolyzed to alkylated acetoacetate derivatives (eq 6). The corresponding reaction with simple alkenes is less general.,-Dianions of acetoacetates (see ) can be generated by treatment with 1 equiv of , followed by 1 equiv of , or 2 equiv of in THF. Reaction of the dianion with a variety of alkylating agents including alkyl halides (eq 7) and epoxides (eq 8) results in regioselective -alkylation.
The Knorr pyrrole synthesis is a widely used chemical ..
Racemic -substituted acetoacetates may also be hydrogenated in high stereoselectivity via dynamic kinetic resolution.A wide variety of five- and six-membered heterocyclic systems may be derived by the cyclocondensation of acetoacetates with 1,2- and 1,3-bifunctional reagents wherein one or both of the functionalities are heteroatomic (Table 1).