Visible‐Light‐Mediated Generation of Nitrogen‐Centered Radicals: Metal‐Free Hydroimination and Iminohydroxylation Cyclization Reactions

Abstract

The formation and use of iminyl radicals in novel and divergent hydroimination and iminohydroxylation cyclization reactions has been accomplished through the design of an ew class of reactive O-aryl oximes.O wing to their low reduction potentials,the inexpensive organic dye eosin Ycould be used as the photocatalyst of the organocatalytic hydroimination reaction. Furthermore,r eaction conditions for au nique iminohydroxylation were identified;v isible-lightmediated electron transfer from novel electron donor-acceptor complexes of the oximes and Et 3 Nwas proposed as akey step of this process.Nitrogen-centered radicals (NCRs) are av ersatile class of intermediates that have wide applications in the synthesis of N-containing molecules (Scheme 1A).[1] However,t he difficulties associated with their generation have significantly thwarted their use in synthetic chemistry.Infact, established methods often rely on the homolysis of difficult-to-construct N À Xb onds and require the use of toxic and hazardous reagents at elevated temperatures. [1a,2] Thed evelopment of amild, selective,and general method to catalytically generate NCRs from readily available precursors would enable the facile construction of many N-heterocycles,w hich are privileged motifs in natural products and therapeutic agents. [3] Photoredox catalysis has emerged as apowerful technique through which single electron transfer (SET) reactions can be performed under mild conditions.[4] MacMillan [5] and coworkers have developed an asymmetric visible-light-mediated amination of aldehydes by enamine catalysis,a nd the groups of Sanford, [6] Lee, [7] Yu, [8] and Luo [9] have reported the photoredox generation of phthalimidyl and saccharyl radicals and their use in Minisci-type reactions.T he groups of Zheng [10] and Knowles [11] have developed am ethod for the photoredox generation of diaryl and aryl alkyl aminium radical cations and employed them in CÀNb ond-forming reactions.Drawing inspiration from the work of Forrester, [12] Narasaka, [13] and Walton, [14] we speculated that appropriately functionalized O-aryl oximes could serve as general, benchstable NCR precursors that could deliver iminyl radicals upon photoredox activation under mild conditions.[15] Such an approach would clearly benefit from the facile synthesis of aryl oximes,and we hoped that the high structural modularity of the O-aryl hydroxylamines would allow us to identify substrates that do not require the use of transition-metalbased photocatalysts.[16] Herein, we describe the successful implementation of this approach and the development of novel, transition-metal-free,v isible-light-mediated hydroimination and iminohydroxylation cyclization reactions (Scheme 1B).Theg uiding principle of our photoredox NCR synthesis capitalized on the evidence that electron-poor aromatic compounds have reduction potentials compatible with SET reduction by visible-light-excited photocatalysts, [17] as shown by MacMillan and co-workers.[18] Our envisaged photoredox iminyl NCR generation was init...

Photokatalyse mit sichtbarem Licht: Welche Bedeutung hat sie für die organische Synthese?

“…Neben Anilinderivaten werden auch 3-Aminopyridin und Sulfonamide umgesetzt. Leonori und Mitarbeiter entwickelten eine photokatalytische Synthese von fünfgliedrigen N-Heterocyclen aus O-Aryloximen [98] und elektronenarmen Aryloxyamiden [99] als Vorstufen von stickstoffzentrierten Radikalen (siehe SI, Schema S7). [91] Ausgehend von 2-Halogenanilinen und Alkenen war die Kombination von Photoredoxkatalyse mit Nickelkatalyse entscheidend fürd ie Vermeidung der b-Hydrideliminierung (Bildung von Heck-Produkten) zugunsten der reduktiven Eliminierung der C-N-Bindung, die die gewünschten Indoline liefert.…”

Synthesis of Arylamines via Aminium Radicals

“…[15] While successful, these reactions have not been employed in mainstream organic synthesis owing to three main limitations:1 )the aromatic compound is ac o-solvent (10-20 equiv);2 )high-energy light (l < 280 nm) is required and 3) the reactions are run in refluxing AcOH/H 2 SO 4 . [15c] We recently developed av isible-light-mediated synthesis of iminyl [16] and amidyl [11c] radicals through reductive SET fragmentation of electron-poor O-aryl oximes and aryloxyamides.W ee nvisaged that such an approach might have enabled access to aminium radicals for direct aromatic amination. In this paper we describe our work in the area that has resulted in ap owerful method for the fast construction of aryl amines (Scheme 1C).…”

“…We recently developed av isible-light-mediated synthesis of iminyl [16] and amidyl [11c] radicals through reductive SET fragmentation of electron-poor O-aryl oximes and aryloxyamides.W ee nvisaged that such an approach might have enabled access to aminium radicals for direct aromatic amination. In this paper we describe our work in the area that has resulted in ap owerful method for the fast construction of aryl amines (Scheme 1C).…”

Alkene Carboarylation through Catalyst‐Free, Visible Light‐Mediated Smiles Rearrangement

“…form an electron-donor complex in solution,w hereby an electron-transfer event can be triggered by the near-UV/shorter wavelengths of blue visible light typicallyu sed in photoredox experiments. [18] Finally,w hen the reaction (conditions as Ta ble 1, entry 7) wass ubjected to three equivalents of TEMPO ((2,2,6,6-tetramethylpiperidin-1-yl)oxyl, the reaction failed to yield 10 a,s upporting the postulated radical character of the mechanism. Based on these results, we propose the pathway in Scheme 3f or the reaction, beginning with TMEDAphotoreduction of bromodifluoroacetate 6 to the radical 13.I ntermolecular addition gives the alkyl radical 8,whichcan undergo Truce-Smiles aryl shift with extrusiono fS O 2 .T he resultant amidyl radical 14 can then undergo hydrogen atom transfer,l ikely from the TMEDA which is present in excess, to yield the C-arylated product 9.…”