Synthesis of densely functionalized enantiopure indolizidines by ring-closing metathesis (RCM) of hydroxylamines from carbohydrate-derived nitrones

Abstract

Background

On the Virtue of Indium in Reduction Reactions. A Comparison of Reductions Mediated by Indium and Zinc: Is Indium Metal an Effective Catalyst for Zinc Induced Reductions?

“…However, the same conditions were inefficient to reduce hydroxylamines closely related to 14 , bearing two vinyl or ethynyl substituents instead of the two allyl groups. On some occasions, preliminary O ‐acetylation was beneficial for the success of N‐O bond reductive cleavage with zinc …”

“…On some occasions, preliminary O-acetylation was beneficial for the success of N-O bond reductive cleavage with zinc. [14] We assume that the efficiency of the In-mediated catalytic reduction method, in comparison with other expectedly more reducing metals on the basis of their reduction potentials (Scheme 2), is due to a rapid initial reduction of the hydroxylamine to amine by In, according to its unusually high first ionization potential. Subsequently, In 0 is regenerated from In I (or In III ) species by a stoichiometric reductant possessing a higher standard reduction potential (in absolute value), such as zinc or aluminium (Scheme 2).…”

Expedient, one-pot preparation of fused indoles via CAN-catalyzed three-component domino sequences and their transformation into polyheterocyclic compounds containing pyrrolo[1,2-a]azepine fragments

“…However, as shown in Scheme 6, the O-acetylated and benzoylated derivatives 14a-d underwent smooth ring-closing reaction in the presence of 10 mol% of Grubbs 1st generation catalyst under mild experimental conditions in dichloromethane to give very good yields of compounds 15, which are derivatives of the hitherto unknown 9,12-dihydro-8H-azepino [1,2-a]benzo [g]indole ring system and are of potential biological interest in view of the varied biological activities known for pyrrolo [1,2-a]azepine derivatives. 17 This efficient transformation is noteworthy in view of the difficulties often associated with the construction of medium-sized rings by RCM, specially from acyclic precursors, owing to entropic factors and transannular repulsions that develop as the ring is formed. 18 Indeed, to our knowledge, the synthesis of compounds 15 constitutes the first example of the preparation of a pyrrolo [1,2a]azepine system by a metathesis strategy.…”