Catalytic Acceptorless Dehydrogenation of Amino Alcohols and 2‑Hydroxybenzyl Alcohols for Annulation Reaction under Neutral Conditions

A base-free and acceptorless Ru-catalyzed dehydrogenative approach has been developed for the synthesis of N-heterocycles by using 1,3-dicarbonyls and amino alcohols through a domino sequential enamine formation and intramolecular oxidative cyclization strategy. This unified approach is also applicable for the synthesis of O-heterocycles involving 2-hydroxybenzyl alcohol as a coupling reactant via consecutive C-alkylation and intramolecular cyclization steps. The present protocol is general for the synthesis of varieties of biologically important scaffolds, such as tetrahydro-4H-indol-4-one, 3,4-dihydroacridin-1­(2H)-one, and tetrahydro-1H-xanthen-1-ones derivatives using a single catalytic system, viz. RuH₂CO­(PPh₃)₃. Environmentally benign H₂O and H₂ are the only byproducts in this domino process. Moreover, RuH₂CO­(PPh₃)₃-catalyzed C3-alkylation of tetrahydro-4H-indol-4-one using alcohol as a alkylating partner is also described in this report. For the first time, a solvent-free gram-scale reaction for the acceptorless dehydrogenative annulation has been demonstrated. A plausible mechanism for the Ru-catalyzed base-free and acceptorless dehydrogenative annulation of amino alcohols or 2-hydroxybenzyl alcohols has been provided with several experimental investigations and spectroscopic evidence.