Solvent-Regulated Coupling of 2-Alkynylbenzaldehydes with Cyclic Amines: Selective Synthesis of Fused N-Heterocycles and Functionalized Naphthalene Derivatives

Abstract

An efficient synthesis of 1,2,3,4-tetrahydrobenzo­[g]­quinoline derivatives through PdCl2-catalyzed, TBHP-promoted, and toluene-mediated dehydrogenation/[4+2] cycloaddition of saturated cyclic amines with 2-alkynylbenzaldehydes was developed. On the contrary, when the reaction medium was changed from toluene to DMSO/H2O, another class of important compounds, naphthyl chain amines, formed via a dehydrogenation–intermolecular condensation–C–N bond cleavage–intramolecular condensation pathway, was obtained with good selectivity.

Organocatalytic Asymmetric Multicomponent Cascade Reaction for the Synthesis of Contiguously Substituted Tetrahydronaphthols

“…Alternatively, if the reactive oxocarbenium ion can be trapped by introduction of an appropriate nucleophile, such as H 2 O, tetrahydronaphthols might be accessed after ring-opening of the in situ generated cyclic hemiacetal. Dienamine catalysis can generate electron-rich olefins and has shown a high degree of stereocontrol in cycloadditions and good compatibility with water .…”

Deconstructive Pyridylation of Unstrained Cyclic Amines through a One-Pot Umpolung Approach

“…(Scheme 1a, down). 7 In 2018, Sarpong et al reported a deconstructive strategy for transforming saturated cyclic amines into acyclic haloamines using silver with an oxidantcontaining halogen group as reagents. 8 To eliminate the use of transition metals and oxidants, difluorocarbene reagents have been used for the C−N bond cleavage of cyclic amines to access the multifaceted acyclic architectures under mild conditions.…”

Oxoammonium Salt-Promoted Multifunctionalization of Saturated Cyclic Amines Based On β-Oxo Cyclic Iminium Ion Intermediates

“…8 Our group developed a PdCl 2 -catalyzed, TBHPpromoted, and toluene-mediated reaction to form α,βdifunctionalized azaheterocycles through the dehydrogenation/[4 + 2] cycloaddition of saturated N-heterocycles with 2-alkynylbenzaldehydes. 9 Recently, Seidel's group achieved α,β-disubstituted or α,β,α′-trisubstituted amines through hydride transfer reactions of N-lithiated amines with a ketone oxidant. 10 Meanwhile, it was noticed that these elegant methods generally furnished functionalized amines with a nucleophilic substituent introduced at the α-site and an electrophilic substituent introduced at the β-site via enamines or endocyclic 1-aza allyl anions as intermediates (Scheme 1A).…”

“…Xu’s group reported an efficient visible-light-photocatalyzed dehydrogenation/[2 + 2] cycloaddition sequence for the functionalization of dual C­(sp 3 )–H bonds in saturated cyclic amines . Our group developed a PdCl 2 -catalyzed, TBHP-promoted, and toluene-mediated reaction to form α,β-difunctionalized azaheterocycles through the dehydrogenation/[4 + 2] cycloaddition of saturated N -heterocycles with 2-alkynylbenzaldehydes . Recently, Seidel’s group achieved α,β-disubstituted or α,β,α′-trisubstituted amines through hydride transfer reactions of N -lithiated amines with a ketone oxidant .…”

“…However, their application in the multifunctionalization of α,β-C­(sp 3 )–H bonds of saturated N -heterocycles is still underdeveloped. In our continuous efforts to pursue the facile construction of diverse drug-like functionalized azaheterocycles, ,, we believe that TEMPO-oxoammonium salt (TEMPO + ) might work as both a dehydrogenating and oxygenating reagent to generate the β-oxo cyclic iminium ion intermediate (Scheme B, ii ) from saturated cyclic amines via dehydrogenation, nucleophilic addition with an oxoammonium salt followed by β-proton transfer, and cleavage of the O–N bond. The in situ formed β-umpolung intermediate ii , bearing both an iminium ion and a carboyl moiety in the skeleton, is expected to react with different nucleophiles to deliver α,β-dual site-multifunctionalized azaheterocycles.…”