Solvent‐Free Non‐Covalent Organocatalysis: Enantioselective Addition of Nitroalkanes to Alkylideneindolenines as a Flexible Gateway to Optically Active Tryptamine Derivatives

Abstract

A catalytic asymmetric addition of nitroalkanes to alkylideneindolenines, generated in situ from arylsulfonylindoles, is presented. Despite the weakness of the non-covalent H-bond interactions between catalyst and substrates, the performance of the bifunctional organocatalyst used was found to be essentially unaffected by the polarity of the reaction medium. Nitroalkanes, mostly used in nearly stoichiometric amounts, could thus function both as sol-vents and reagents, resulting in a truly solvent-free reaction. The broad substrate scope shown by the present transformation allowed the preparation of some optically active tryptamine precursors that are not accessible through the previous catalytic asymmetric methods.

Catalytic Asymmetric Addition of Meldrum’s Acid, Malononitrile, and 1,3‐Dicarbonyls to ortho‐Quinone Methides Generated In Situ Under Basic Conditions

“…Cyclizations at the phenolic oxygen follow the nucleophilic additions, affording 3,4-dihydrocoumarins 4 and 4H-chromenes 5 and 6.T hese structures are privileged scaffolds in medicinal andn atural product chemistry (vide infra). [17] At the outset of this work, on the basis of our experience [18] and related literature data on the in situ generation of imines and alkylidenendolenines by sulfinic acid elimination, [19] we explored combinations of bifunctionalo rganic catalysts, inorganic bases, and variousc ommon activem ethylene compounds in the reaction with the 5-methoxysalicylaldehyde derivedsulfone 1a.I nl ine with previoust actics, [10] we focusedo nt his sulfone 1a for our initial studies reasoningt hat its methoxy group would favour formation of the o-QM intermediate, and stabi-lize it. [1d] After considerable experimentation, encouraging reactivity was observed with Meldrum's acid, which furnished the 3,4-dihydrocoumarin 4a,r esulting from cyclization and ensuing decarboxylation of the intermediate adduct [Eq.…”

Recent Advances in Solvent‐Free Asymmetric Catalysis

“…In 2012, double hydrogen donors or single sulfonamide donor organocatalysts were applied for the addition of nitroalkanes to alkylideneindolenines to the synthesis of tryptamine derivatives . Reactions were performed under neat conditions using an excess of nitroethane could thus act both as solvent and reagent, with several tertiary amino bifunctional catalysts systems in the presence of different inorganic bases.…”

Imine and iminium precursors as versatile intermediates in enantioselective organocatalysis

“…112 They developed a solvent free protocol, eventually performing the reaction with only 1.5 equiv of nitroalkane. For the activation of the electrophile, K 3 PO 4 was discovered to be the optimal base.…”