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.