Radical Heterocyclization and Heterocyclization Cascades Triggered by Electron Transfer to Amide‐Type Carbonyl Compounds

Huang, Huan‐Ming; Procter, David J.

doi:10.1002/anie.201708354

Cited by 30 publications

(12 citation statements)

References 107 publications

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“…11,12 As a result, SmI 2 can be used to selectively reduce a particular functional group in a multifunctional substrate for follow-up bondforming reactions and is exceptionally effective in reductive couplings, [13][14][15][16][17][18][19][20][21][22] and cascade reactions. [23][24][25][26][27][28][29][30][31][32][33][34][35] Most importantly, its use allows for alternative and selective methods for the synthesis of multifunctional targets. 4,9 While numerous reactions have been developed for SmI 2 , its scope in synthesis certainly has not been exhausted and new applications for this reagent are steadily being discovered.…”

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confidence: 99%

Mechanistic Study and Development of Catalytic Reactions of Sm(II)

Maity

Flowers

2019

J. Am. Chem. Soc.

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Despite the broad utility and application of SmI 2 in synthesis, the reagent is used in stoichiometric amounts and has a high molecular weight, resulting in a large amount of material being used for reactions requiring one or more equivalents of electrons. We report mechanistic studies on catalytic reactions of Sm(II) employing a terminal magnesium reductant and trimethyl silyl chloride in concert with a non-coordinating proton donor source. Reactions using this approach permitted reductions with as little as 1 mol% Sm. The mechanistic approach enabled catalysis employing HMPA as a ligand, facilitating the development of catalytic Sm(II) 5-exo-trig ketyl olefin cyclization reactions. File list (3) download file view on ChemRxiv Sm(II) Catalysis (RAF).pdf (746.24 KiB) download file view on ChemRxiv SI_Sm(II) catalysis.pdf (3.10 MiB) download file view on ChemRxiv Sm(II) Catalysis (RAF).doc (574.50 KiB)

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confidence: 99%

Mechanistic Study and Development of Catalytic Reactions of Sm(II)

Maity

Flowers

2019

J. Am. Chem. Soc.

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“…Unfortunately, the formation of ketyl‐type radicals is typically limited to aldehyde or ketone substrates, regardless of the reagent used for radical generation. Recently, we and others have begun to extend the rich chemistry of ketyl‐type radicals to the reductive cyclizations of carboxylic acid derivatives, including cyclic esters– and cyclic amide derivatives,– possessing more electron‐rich carbonyls. However, engaging carbonyl‐containing substrates in which the carbonyl is flanked by two heteroatom substituents in ketyl‐type radical chemistry, until now, has not proved possible, despite the promise of new reaction space for exploration.…”

Section: Methodsmentioning

confidence: 99%

Radical Anions from Urea‐type Carbonyls: Radical Cyclizations and Cyclization Cascades

2018

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Radical anions generated from urea carbonyls by reductive electron transfer are exploited in carbon-carbon bond formation. New radical cyclizations of urea radical anions deliver complex nitrogen heterocycles and, depending upon the proton source used in the reactions,achemoselective switch between reaction pathwaysc an deliver two heterobicyclic scaffolds.Acomputational study has been used to investigate the selectivity of the urea radical processes. Furthermore,r adical cyclization cascades involving urea radical anions deliver unusual spirocyclic aminal architectures.Carbon-carbon bond formation is integral to almost any synthetic endeavor and provides af ocal point for contemporary synthetic method development. [1] Radical reactions constitute one of the most important and attractive tools to achieve carbon-carbon bond formation. [2] In particular, radical cyclizations and cyclization cascades are prized for their ability to construct carbo and heterocyclic motifs, including those found in complex natural products,b iologically active molecules and materials. [3] Within radical chemistry,k etyl radicals,t ypically derived by single electron transfer (SET) reduction of aldehydes and ketones,h old high status as one of the most important and versatile classes of open shell intermediates for use in synthesis. [4] Cyclization reactions involving ketyl radicals inherently give oxygenated cyclic products,o ften possessing valuable three-dimensional shape,and have been achieved by deploying reagents based on Sm II , [5] Ti III , [6a-e] Ru II , [6f-i] Ir III , [6j] and electrochemistry, [6k] amongst others. [4] In particular, samarium(II) iodide (SmI 2 )i st he reagent most frequently used to generate ketyl radicals and the reactive intermediates formed in this way have found widespread application in myriad cyclization and cyclization cascade strategies [5] thus establishing both reagent and reaction as standard tools for synthesis. [7] Unfortunately,t he formation of ketyl-type radicals is typically limited to aldehyde or ketone substrates, regardless of the reagent used for radical generation. Recently,w ea nd others have begun to extend the rich chemistry of ketyl-type radicals to the reductive cyclizations of carboxylic acid derivatives, [8a] including cyclic esters [8b-d] and cyclic amide derivatives, [8e-k] possessing more electronrich carbonyls.H owever,e ngaging carbonyl-containing sub-[*] Dr.

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“…Impressive functional group tolerance has been demonstrated, including aryl halides, ethers and heterocycles. This elegant process sets the stage for the design of a plethora of dearomatizing cyclizations for the synthesis of nitrogen heterocycles via aminoketyl radicals [ 38 , 39 ].…”

Section: Synthesis Of Nitrogen Heterocycles Via Aminoketyl Radicalmentioning

confidence: 99%

Synthesis of Nitrogen Heterocycles Using Samarium(II) Iodide

Shi

Szostak

2017

Molecules

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Nitrogen heterocycles represent vital structural motifs in biologically-active natural products and pharmaceuticals. As a result, the development of new, convenient and more efficient processes to N-heterocycles is of great interest to synthetic chemists. Samarium(II) iodide (SmI2, Kagan’s reagent) has been widely used to forge challenging C–C bonds through reductive coupling reactions. Historically, the use of SmI2 in organic synthesis has been focused on the construction of carbocycles and oxygen-containing motifs. Recently, significant advances have taken place in the use of SmI2 for the synthesis of nitrogen heterocycles, enabled in large part by the unique combination of high reducing power of this reagent (E1/2 of up to −2.8 V) with excellent chemoselectivity of the reductive umpolung cyclizations mediated by SmI2. In particular, radical cross-coupling reactions exploiting SmI2-induced selective generation of aminoketyl radicals have emerged as concise and efficient methods for constructing 2-azabicycles, pyrrolidines and complex polycyclic barbiturates. Moreover, a broad range of novel processes involving SmI2-promoted formation of aminyl radicals have been leveraged for the synthesis of complex nitrogen-containing molecular architectures by direct and tethered pathways. Applications to the synthesis of natural products have highlighted the generality of processes and the intermediates accessible with SmI2. In this review, recent advances involving the synthesis of nitrogen heterocycles using SmI2 are summarized, with a major focus on reductive coupling reactions that enable one-step construction of nitrogen-containing motifs in a highly efficient manner, while taking advantage of the spectacular selectivity of the venerable Kagan’s reagent.

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Radical Heterocyclization and Heterocyclization Cascades Triggered by Electron Transfer to Amide‐Type Carbonyl Compounds

Cited by 30 publications

References 107 publications

Mechanistic Study and Development of Catalytic Reactions of Sm(II)

Mechanistic Study and Development of Catalytic Reactions of Sm(II)

Radical Anions from Urea‐type Carbonyls: Radical Cyclizations and Cyclization Cascades

Synthesis of Nitrogen Heterocycles Using Samarium(II) Iodide

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