The Cleavage of a CC Bond in Cyclobutylanilines by Visible‐Light Photoredox Catalysis: Development of a [4+2] Annulation Method

Abstract

Abstract:We report the first example of an intermolecular [4+ +2] annulation of cyclobutylanilines with alkynes enabled by visible-light photocatalysis.M onocyclic and bicyclic cyclobutylanilines successfully undergo the annulation with terminal and internal alkynes to generate aw ide variety of aminesubstituted cyclohexenes including new hydrindan and decalin derivatives with good to excellent diastereoselectivity.T he reaction is overall redox neutral with perfect atom economy.The release of ring strain has often been exploited as adriving force to promote the cleavage of typically unreactive bonds such as carbon-carbon bonds.[1] This strategy has been successfully applied to the ring opening of cyclopropanes, which leads to the wide use of cyclopropanes in organic synthesis.[2] We recently reported visible-light-promoted [3+ +2] annulation reactions of cyclopropylanilines with various p bonds.[3] In these reactions,t he cleavage of the cyclopropyl rings is promoted by photooxidation of the parent amine to the corresponding amine radical cation. Since the oxidation potentials of cyclopropylaniline and cyclobutylaniline were found to be similar, [4] we were intrigued by the possibility of using cyclobutylanilines in asimilar manner in the annulation reactions.W ewere further encouraged by the fact that cyclobutanes strain energy is almost identical to that of cyclopropane. [5,6] Still, the ring opening of cyclopropanes is generally much faster than that of cyclobutanes.Newcomb et al. reported that the rate constant for ring opening of ac yclobutylcarbinyl radical was 1.5 10 3 s À1 at 20 8 8Cc ompared to 710 7 s À1 at 20 8 8Cf or ring opening of ac yclopropylcarbinyl radical. [7] Ingold et al. reported the rate constant for ring opening of the cyclobutyl-n-propylaminyl radical to be 1.2 10 5 s À1 at 25 8 8Cw hereas the rate constant was estimated to be greater than 10 7 s À1 at 25 8 8Cf or ring opening of the cyclopropyl-npropylaminyl radical (Scheme 1). [8] Thep roposed ring opening of the cyclobutylaniline radical cation was expected to be faster than the neutral aminyl radical, [9] which lent further credence to the proposed annulation reaction. Surprisingly,to the best of our knowledge,there have been no reports of using cyclobutylanilines in the tandem ring opening and annulation sequence to construct six-membered carbocycles.T his is in contrast to the increasing use of other types of cyclobutanes in the tandem sequence.[10] Successful ring opening of these cyclobutanes usually relies on the decoration of the cyclobutyl ring with donor-acceptor [11] or ketone/hydroxy functionalities.[12] Herein we describe the successful development of the [4+ +2] annulation of cyclobutylanilines with alkynes by visiblelight photoredox catalysis,w hich greatly broadens the use of cyclobutanes as af our-carbon synthon in organic synthesis. We hope that this method will add to the growing pool of synthetic methods based on photocatalysis. [13] We chose 4-tert-butyl-N-cyclobutylaniline 1a and phenylacetylene 2a as the standard...

Photoinduced Remote Functionalisations by Iminyl Radical Promoted C−C and C−H Bond Cleavage Cascades

“…The development of methods for the selective functionalisation of non-activated sp 3 carbon atoms is al ongstanding endeavour in organic synthesis. [1] Radical strategies are attractive options owing to the ability of odd-electron species to undergo transposition processes.…”

“…[1] Radical strategies are attractive options owing to the ability of odd-electron species to undergo transposition processes. [2] If as uitably reactive radical is generated in as pecific position of an organic molecule,t hen C(sp 3 ) À C(sp 3 )a nd C(sp 3 ) À Hb ond cleavage can be triggered, leading to remote functionalisations.C lassical examples are the ring opening of a-cyclopropyl radicals (radical clock) [3] and the 1,5-hydrogen atom abstraction of nitrogen radicals-the key step of the Hofmann-Lçffler-Freytag (HLF) reaction [4] (Scheme 1A). [5] We have recently developed two classes of oximes that provide access to iminyl radicals by both reductive and oxidative visible-light-mediated single electron transfer (SET) and employed them in intramolecular cyclisation processes (Scheme 1B).…”

“…In conclusion, we have developed aphotoinduced strategy for the preparation of remotely functionalised nitriles and ketones.T hese reactions are triggered by the organophotoredox generation of iminyl radicals that give access to distal carbon radicals upon transposition by C(sp 3 ) À C(sp 3 )o r C(sp 3 ) À Hb ond cleavage.…”

Oxidative Fluorination of Cyclopropylamides through Organic Photoredox Catalysis

“…[7] Zheng and coworkers have demonstrated that cyclopropylanilines and cyclobutylanilines can be oxidized to a radical cation species I using photoredox catalysis (Scheme 1 C). [8] After ring opening, the resulting iminium radical II underwent (3+2) annulation with alkenes or alkynes. Our group later extended this approach to cyclopropenes, [9] and Stephenson and coworkers applied it to the synthesis of 1-aminonorbornanes.…”