Exploiting alcohols as Alkylating Agents of Heterocyclic Nucleophiles through the “Borrowing Hydrogen” Process

The work presented in this thesis is focused on the use of alcohol as green alkylating agents to develop novel synthetic routes using borrowing hydrogen methodology to synthesize small molecules and biologically active natural products. In particular, the synthesis of substituted tryptamine derivatives starting from indoles and amino alcohols via the borrowing hydrogen process are discussed. This catalytic single-step, and modular approach to tryptamines and homotryptamines allows the synthesis of branched and non- branched tryptamines as well as tryptamine-based natural products such as psilocin, bufotenin, and serotonin. Than oxindoles are taken in consideration, they display a diverse pattern of reactivity upon reaction with different classes of amino alcohols via the borrowing hydrogen process. Whereas the reaction with N-acetyl amino alcohols leads to C3 alkylation, the reaction with primary N-benzyl aminoalcohols results in the formation of synthetically useful α-aryl-γ-lactams via a remarkably facile oxindole ring-opening reaction. Finally the coupling of primary and secondary benzyl alcohols with indoles to form 3-benzylated indoles catalyzed by a complex of earth-abundant iron is presented. This transformation accommodates a variety of substrates and is distinguished by its operational simplicity, sustainability, high functional-group tolerance, and amenability to gram-scale synthesis. On the basis of the preliminary experimental observations, the reaction proceeds through a borrowing hydrogen process.