Rapid Construction of Complex 2-Pyrrolines through Lewis Acid-Catalyzed, Sequential Three-Component Reactions via in Situ-Generated 1-Azaallyl Cations

Abstract

The first Sc(OTf)-catalyzed dehydration of 2-hydroxy oxime ethers to generate benzylic stabilized 1-azaallyl cations, which are captured by 1,3-carbonyls, is described. A subsequent addition of primary amines in a sequential three-component reaction affords highly substituted and densely functionalized tetrahydroindeno[2,1- b]pyrroles as single diastereomers with up to quantitative yield. Thus, three new σ-bonds and two vicinal quaternary stereogenic centers are generated in a one-pot operation.

Iron(III)-Catalyzed (4 + 2)-Cycloannulation of 2-Hydroxy Ketoxime Ethers with Indol-2-ylamides: Synthesis of Indole-Fused 2-Piperidinones

“…2-Hydroxy ketoxime ethers 5a – i were synthesized according to procedures by Schneider et al , Indol-2-ylamine 8 and N -alkyl indol-2-ylamide 9 were synthesized according to literature procedures . The structures of all starting materials are displayed in Figure S1 of the SI.…”

“…8 We have recently established various Lewis acid catalyzed transformations of 2-hydroxy ketoxime ethers 5 including highly versatile Friedel−Crafts reactions (FCRs) 9 as well as multicomponent reactions toward complex 2-pyrrolines. 10,11 We proposed that these reactions proceeded through putative 1-azaallyl cations and provided computational evidence for their intermediacy. 10 Based upon these studies, we envisioned novel (4 + 2)-cycloannulation reactions when 1,4-bisnucleophiles were employed to capture the intermediate 1-azaallyl cations.…”

Acid-Mediated Cascade Cyclization Pathway to Indeno[2,1-c]chromen-6(7H)-ones

“…For instance, the Lewis/Brønsted acid-mediated cascade or domino organic transformation reaction for synthesizing valuable carbocyclic and heterocyclic organic frameworks from reasonably simple starting materials is a powerful tool in organic chemistry. ,,− In this context, in 2012 and 2013, the Dattatraya group reported the iron­(III) chloride-induced synthesis of indene skeleton-based molecules starting from the o -alkene-tethered cinnamates, and in 2015, the same research group described the synthesis of indanone molecules from ortho -carbonyl-tethered cinnamates via iron­(III) chloride-mediated cyclization. As a continuation, Balamurugan et al in 2021 presented the triflic acid-catalyzed domino cyclization pathway for synthesizing indene derivatives.…”

Synthesis of Acyl Fluorides via DAST-Mediated Fluorinative C–C Bond Cleavage of Activated Ketones

“…Setting out the research, the model substrate 1a was prepared. α-Oximation of ketones is readily accessed in several ways: direct formation at the ketone α-position by acid- or base-assisted oximation using alkylnitrites, condensation between hydroxylamine and 1,2-diketones, , or nitroso-interception by silyl enol ethers . After surveying some nucleophilic fluorinating reagents, we found that the simple addition of DAST to 1a provided the acyl fluoride 2a in the highest yield (Table , entry 1).…”