Synthetic and Computational Study of Tin-Free Reductive Tandem Cyclizations of Neutral Aminyl Radicals

Abstract

5-exo, 5-exo Cyclizations of conformationally unbiased propargylic aminyl radicals proceed with excellent yield, chemoselectiv ity, and diastereoselectivity under tin-free reductive cyclization conditions, regardless of the electronic environments and intermediate radical stabilization resulting from various olefin substituents. These conditions avoid the need for slow addition of initiator and reductant. By contrast, analogous 6-exo, 5-exo cyclizations require substituents capable of intermediate radical stabilization to avoid premature reduction products. These experimental results are corroborated by computations that further establish the reactivity of these aminyl radicals upon exposure to tin-free cyclization conditions.

Directed Copper-Catalyzed Intermolecular Aminative Difunctionalization of Unactivated Alkenes

“…Neale and Minisci have made great contributions to the intermolecular aminochlorination of unactivated alkenes four decades ago utilizing N -chlorodialkylamines in strongly acidic solutions, with only a few cases employing metal salts to give aminochlorination products in low yields . Since then, the studies of aminochlorination of unactivated alkenes mainly focused on intramolecular processes or the nitrogen source containing electron-deficient substituents, ,, and recently an iron-catalyzed aminochlorination reaction by Morandi and co-workers offered an efficient access to primary amines . Moreover, the intermolecular aminobromination of unactivated alkenes with a dialkylamino source has not yet been realized.…”

“…When the efficiency of the C–N bond formation is low, these fleeting alkyl ARC species can either immediately convert to α-amino radicals by deprotonation of the α-carbon atom or abstract a hydrogen to generate iminium ions . The Knowles group has recently disclosed an elegant photodriven protocol for the intermolecular hydroamination of unactivated alkenes that proceeds through alkyl ARC intermediates (Figure B), whereas the alkyl aminative difunctionalization of unactivated alkenes via a radical pathway is still restricted to either intramolecular versions or carried out under strongly acidic conditions . An alternative solution, developed by Wang and Liu, obtains a variety of amino heterocycles via a sequential inter- and intramolecular pathway wherein the nucleophiles are tethered and O -benzoylhydroxylamines are used to initiate the electrophilic activation of the aliphatic alkenes (Figure C).…”

Novel Sources of Drug Components in Plants

“…This survey ef iciently talks about the current advancement with respect to the potential enemy of common items and regular item motivated little particles. [4]…”

Modular and practical diamination of allenes

“…To further explore the reaction mechanism, alkyl amines 57, 60, and 63 were prepared. For 57 and 60, if an amino radical is formed, cascade radical cyclization products such as 59 and 62 could be formed 73 . After 57 was treated with t-BuOCl, then TBAI, product 58 was formed in 28% yield (Fig.…”