ABSTRACT
An efficient continuous flow process for the macrolactonization of seco acids and diacids using diols in the presence of Mukaiyama reagent (N-methyl-2-chloropyridinium iodide) has been developed for medium to large sized macrocyclic lactones. In comparison with other methods, the continuous flow process provided good to high yield in a short reaction time. By using this methodology, a wide range of macrocyclic lactones (11 compounds), dilactones (15 compounds), and tetralactone derivatives (2 compounds) with various ring sizes (12-26 atoms in the core) were synthesized in just 35 min of residence time. Advantageously, macrolactonization under the flow process is very elegant to handle the high dilution of reactants with a defined perfluoroalkoxy alkanes (PFA) tube reactor volume (7 mL).
ABSTRACT
Herein, we have developed a new approach for the synthesis of 11 to 21-membered macrolactones via intramolecular dehydrogenative coupling of primary alcohols by using Ru-MACHO as a catalyst and Cs2CO3 as a base. This protocol generated 11-21-ring-sized macrocycles (26 derivatives), free from an external oxidant or an additive, eliminating stoichiometric reagents and producing only hydrogen as a byproduct.
Subject(s)
Hydrogen , Catalysis , Indicators and ReagentsABSTRACT
Herein we describe a new approach for end-to-end cyclization to construct macrocycles through the inter/intramolecular dehydrogenative coupling of alcohols and ketones in the presence of a Ru-MACHO catalyst. This method is highly atom economical and sustainable and can be used for many substrates. Additionally, this method results in the generation of only water as the byproduct. Moreover, in this approach, high dilution of the reactants is crucial for cyclization and high-yield macrocycle synthesis.
ABSTRACT
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.
