Acetylenic esters synthesis

Alkynes undergo stoichiometric oxidative reactions with Pd(II). A useful reaction is oxidative carboiiyiation. Two types of the oxidative carbonyla-tion of alkynes are known. The first is a synthesis of the alkynic carbox-ylates 524 by oxidative carbonylation of terminal alkynes using PdCN and CuCh in the presence of a base[469], Dropwise addition of alkynes is recommended as a preparative-scale procedure of this reation in order to minimize the oxidative dimerization of alkynes as a competitive reaction[470]. Also efficient carbonylation of terminal alkynes using PdCU, CuCI and LiCi under CO-O2 (1 I) was reported[471]. The reaction has been applied to the synthesis of the carbapenem intermediate 525[472], The steroidal acetylenic ester 526 formed by this reaction undergoes the hydroarylalion of the triple bond (see Chapter 4, Section 1) with aryl iodide and formic acid to give the lactone 527(473],... 

The addition of secondary amines to acetylenes is most applicable to the synthesis of conjugated acyclic enamines (50,171,172). Particularly the addition to acetylenic esters and sulfones has been investigated (173-177) and it appears that an initial trans addition is followed by isomerization to more stable products where the amine and functional group are in a trans orientation (178). Enamines have also been obtained by addition of secondary amines to allenes (179). 

The Fiesselmann thiophene synthesis involves the condensation reaction of thioglycolic acid derivatives with a,P-acetylenic esters, which upon treatment with base results in the formation of 3-hydroxy-2-thiophenecarboxyIic acid derivatives. 

Synthesis of Heterocycles through Nucleophilic Additions to Acetylenic Esters... 

The present review is intended to highlight the use of acetylenic esters in the synthesis of different heterocycles, primarily involving nucleophilic additions. The reactions of heterocyclic bases with acetylenic esters, however, will not be covered here, except in a few cases where it is more appropriate for inclusion here, depending on the type of reactions. The reactions of heterocyclic bases form the subject matter of a separate article. The survey covers the literature up to December 1973. 

Hendrickson and co-workers have used the reaction of a-amino-ketones with acetylenic esters for synthesizing pyrrole derivatives. Thus, in the reaction of a-aminopropiophenone with DMAD, an intermediate enamine adduct (56) is formed, which ultimately gives rise to the pyrrole 57 in presence of methanolic HCl [Eq. (16)]. Pandit and Huisman have shown the generality of this scheme in the synthesis of polycyclic pyrrole derivatives. 

Secondary amines, such as dimethylamine, diethylamine, diisopropylamine, dicyclohexylamine, A(-methylaniline, aziridine, and azetidine, are reported to undergo cis addition to acetylenic esters, giving rise to simple 1 1 Michael adducts, in each case. These adducts have been successfully employed in the synthesis of different heterocyclic compounds. 

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