Steglich coupling reaction

In order to couple the two p-hydroxyleucine monomers, an EDC-based Steglich coupling reaction was used (Scheme 9). To our surprise the reaction did not work at all, yielding only a mix of the starting materials and minor side products. This was initially surprising because as the reaction was monitored via TLC the disappearance of the acid starting material was observed. As illustrated in Fig. 7, the TLC obtained from the crude reaction product showed two spots. One was attributed to the starting alcohol and the other... 

The Paal-Knorr reaction was also employed by Steglich in likely biomimetic approaches to the marine alkaloids lamellarin L <00CEJ1147> as well as purpurone and ningalin C <00TL9477>. The overall approach employed herein involved initial oxidative coupling of two arylpyruvic acids followed by condensation of the resulting 1,4-diketones with suitable... 

Alternative reactions employ coupling reagents such as DCC (Steglich Esterification), preformed esters (transesterification), carboxylic acid chlorides or anhydrides. These reactions avoid the production of water. Another pathway for the production of esters is the formation of a carboxylate anion, which then reacts as a nucleophile with an electrophile (similar reactions can be found here). Esters may also be produced by oxidations, namely by the Baeyer-Villiger oxidation and oxidative esterifications. 

The ability of palladium to mediate decarboxylations of certain heteroaromatic carboxylates was demonstrated by Steglich et al. for intramolecular couplings, as well as by Forgione and Bilodeau for intermolecular couplings (Scheme 16) [56-58]. However, the scope of this reaction indeed seems to be more limited than its bimetallic counterpart. It so far includes mainly five-ring heteroarenes with carboxylate groups in the 2-position. AUcynylcarboxylic acids have also been decarboxylatively coupled with palladium alone [59]. 

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