Well-defined zinc(ii) catalysts for sustainable synthesis of bis(indolyl)methanes via the activation of aromatic and aliphatic alcohols

Abstract

This study presents the synthesis of bis(indolyl)methanes (BIMs) via the activation of primary alcohols serving as alkylating agents, enabled by zinc(II) complexes. Two phosphine-free NNN-type bis(iminopyridine) pincer innocent ligands, designated L1 and L2, were employed to synthesize the Zn(II) catalysts, referred to as Zn1 and Zn2. A detailed characterization of these catalysts was conducted using UV-vis, IR, NMR, and high-resolution mass spectrometry (HRMS), with their solid-state structures verified through single-crystal X-ray diffraction. Zn1 and Zn2 exhibited effective catalytic activity in the C3-alkylation of indoles using both aliphatic and aromatic primary alcohols, resulting in 51 BIM derivatives with isolated yields reaching 92%. Numerous bioactive BIM derivatives, such as vibrindole, arundine, arsindoline A, ST1385, and turbomycin B, were effectively produced using this method. Competitive alkylation experiments were performed to evaluate the substrate preference of aliphatic versus aromatic alcohols. Mechanistic insights were obtained via control experiments and spectroscopic techniques, revealing notable zinc-based intermediates within the catalytic cycle.