Oxidative Transformations of Alkynes and Allenes for Cyclizations and Cross-Couplings

Abstract

Alkynes and allenes are one of the most readily available starting materials having π-bonds. Electrophilic activation of alkynes and allenes under gold-catalysis or Brønsted acid-catalysis could generate cationic intermediates and their proper analysis leads to the various transformations generating complex structural motifs in short steps. The present dissertation demonstrates selective oxidative transformations of alkynes and allenes for cyclizations and cross-couplings under homogeneous catalytic conditions. In the first study, an unprecedented oxygenative cleavage of electron-deficient C-C triple bonds was demonstrated for the process of gold-catalyzed cyclization of 1,6-enynes, affording synthetically useful 1,4-dicarbonyl compounds. While cyclobutenes were reported to form under argon, changing the atmosphere to air resulted in the unexpected aerobic oxidative triple-bond cleavage from the strained fused cyclobutene intermediates. This radical process is particularly appealing because it uses the atmospheric pressure of air as an end-oxidant and completely atom economical. Next, the gold redox cycling was explored to achieve challenging C(sp2)-C(sp2) cross-coupling of vinyl golds with aryl diazonium salts. Combined with the complexity-generating power of gold catalysis, a cross-coupling involving C(sp2)-Au species would be a powerful strategy. It was found that, a photo-generated aryl radical can oxidize Au(I) into Au(III) via single electron transfer, for an efficient C(sp2)-C(sp2) cross-coupling. The oxidative addition pathway was faster than competing proto-demetalation and an efficient cascade cyclization/cross coupling of allenoates with arene diazonium salts was successfully developed under dual Au-and photo redox-catalysis, yielding synthetically useful β-arylated butenolides. Finally, transformation that deals with a ‘metal-free’ approach to access carbene synthons was sought. The activation of readily available polarized alkyne (ynamide) under Brønsted-acid catalysis resulted in a keteniminium ion. The N-oxide attack to this cationic intermediate leads to an ‘umpolung-enolate’, which mimic a synthetic surrogate of α- carbonyl carbocation. Due to its high electrophilic nature, it undergoes a facile and chemo selective inter-molecular nucleophilic attack by nucleophiles in SN2’ fashion, forming a new C-C bond. This method turned out to be an efficient and general for a range of nucleophiles such as indoles, pyrroles, anilines, phenols and silyl enol ethers yielding synthetically important 1,1-di(hetero)aryl amides in good to excellent yields.