The development of one-pot, multi-component and transition-metal-catalyst free synthetic protocol for N-heterocycles is a green and sustainable approach. The solvent plays a critical role in such catalyst free reactions as it constitutes the major portion of reaction mass and facilitates the stabilization of intermediates for the efficient product formation. We herein report a one-pot and catalyst-free tandem coupling among indole, aldehyde and tetrahydroisoquinoline (THIQ) to afford C1-indolyl-N-alkyl THIQ in biodegradable PEG600 solvent. The present method is found to be highly efficient (42–92%) with broad substrate scope. Further, the E-factor (0.3) of the present catalyst-free system is much better (5–593 times) than the previously reported catalyzed methodologies on virtue of recoverable PEG600 solvent. Overall, these results demonstrate a facile and environmentally benign approach for direct C1-functionalization of THIQ in biodegradable and recoverable solvent making it an industrially relevant methodology in near future.

为N杂环开发一锅，多组分和无过渡金属催化剂的免费合成方案是一种绿色且可持续的方法。溶剂在这种无催化剂的反应中起关键作用，因为它构成反应物料的主要部分，并有助于稳定中间体以有效形成产物。我们在本文中报道了吲哚，醛和四氢异喹啉（THIQ）之间的一锅和无催化剂的串联偶联，以提供C1-吲哚基-N可生物降解的PEG600溶剂中的T-烷基THIQ。发现本方法在广泛的底物范围内是高效的（42–92％）。此外，凭借可回收的PEG600溶剂，本无催化剂体系的E因子（0.3）比以前报道的催化方法好得多（5–593倍）。总体而言，这些结果证明了THIQ在可生物降解和可回收溶剂中直接C1官能化的简便，环保的方法，使其在不久的将来成为一种与工业相关的方法。