Publication
The development of efficient synthetic methodologies is crucial to access complex molecules in an economic, eco-friendly and safe way. The reversal of the intrinsic reactivity of functional groups, called Umpolung, allows alternative synthetic strategies and can improve synthetic efficiency. In this thesis, two new Umpolung methods have been investigated. First a novel approach for the direct alkynylation of aromatic C-H bonds has been developed to access aromatic alkynes. Secondly, novel bifunctional (thio)urea carbene catalysts have been synthesized and their use in asymmetric intermolecular heterocouplings has been investigated. Aromatic alkynes are compounds of utmost prominence as synthetic intermediates and for application in materials science. Classical synthetic methods require a prefunctionalization of the aromatic ring in addition to the alkynylation step. An alternative emerging strategy to introduce triple bonds is based on the Umpolung of acetylenes by the use of electrophilic acetylene reagents. In addition, the use of metal catalysis has recently arisen to couple aromatic C-H bonds with electrophiles in a single step. However, direct alkynylation has been only scarcely investigated. In this thesis, alkynyl hypervalent iodines, highly electrophilic acetylenes, were used for the metal-catalyzed direct alkynylation of aromatic C-H bonds. Indoles were alkynylated in C3 position using AuCl as catalyst and TIPS-EBX (1- [(triisopropylsilyl)ethynyl]-1λ3,2-benziodoxol-3(1H)-one) as source of electrophilic acetylene. The reaction proceeded under mild open-flask conditions (room temperature under air, commercial solvents). Importantly, it was the first example showcasing the superiority of alkynyl benziodoxolones over alkynyl iodoniums in alkyne transfer reactions. On contrary to other alkynylation methods, which have either a limited scope or require indole protection, this reaction tolerated a large range of functional groups and worked for unprotected indoles. Furthermore in the presence of pyridine, pyrroles were alkynylated in C2 position in high yields. This development was important in light of the instability of unprotected halogeno- pyrroles, which makes their use in cross-coupling reactions difficult. A one-pot 2- alkynylaniline cyclization/direct alkynylation was next developed. The influence of substituents on the acetylene, the iodoxole ring structure and the benzene ring substitution on the alkynyl benziodoxolones were examined. This study revealed that bulky silyl groups were ideal alkyne substituents. Preliminary mechanistic investigations indicated that the reaction proceeded either via a π activation mechanism or via an oxidative AuI/AuIII mechanism. iii Unfortunately it has not yet been possible to distinguish between both mechanisms. The alkynylation of electron-rich arenes was next explored. N,N-dialkylanilines were alkynylated with high para regioselectivity using iPrOH as solvent. This transformation represented the fir
Qian Wang, Jieping Zhu, Takuji Fujii