Intramolecular acetylide-aldehyde addition

The total synthesis of the marine-derived diterpenoid sarcodictyin A was accomplished in the laboratory of K.C. Nicolaou. The most challenging part of the synthesis was the construction of the tricyclic core, which contains a 10-membered ring. This macrocycle was obtained by the intramolecular 1,2-addition of an acetylide anion to an a, 3-unsaturated aldehyde. This unsaturated aldehyde moiety was installed by utilizing the Knoevenagel condensation catalyzed by (3-alanine. The Knoevenagel product was exclusively the ( )-cyanoester. 

The synthesis of a series of 6,6-bisbenzannulated spiroketals has been achieved by a novel microwave-assisted double intramolecular hetero-Michael addition approach, with good yield (Choi et al, 2009). In this synthesis, coupling of an aryl acetylene and an aryl aldehyde led to an alky mol via acetylide anion addition, which was followed by oxidation to give the desired ynone. Spirocyclization afforded bis-benzannulated spiroketals. 

The processes must be oxidative for inclusion. Metals such as copper and iron can catalyze the addition of allgmes to amines in a CDC process that is presumed to involve an intermediate iminium ion and formation of metal acetylides as the reactive nucleophiles. The oxidative component of this reaction is the generation of the iminium ion. The corresponding non-oxidative process, the aldehyde-allg ne-amine (A ) coupling, will not be a focus here and has been recently reviewed. Interesting intramolecular processes such as cyclizations involving hydride transfers that are overall redox neutral must be similarly excluded. ... 

---