Phthalimides as Exceptionally Efficient Single Electron Transfer Acceptors in Reductive Coupling Reactions Promoted by Samarium Diiodide

Vacas, Tatiana; Álvarez, Eleuterio; Chiara, José Luis

doi:10.1021/ol7023357

Cited by 29 publications

(16 citation statements)

References 24 publications

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“…Due to the fact that phthalimides are effective single electron transfer acceptors,11,12 we envisioned that the reductive coupling of carbonyl substrates of phthalimide with activated alkenes could also be achieved by a Zn‐NH 3 reductive system; under ketyl radical initiation conditions. Thus, we examined the reaction of N ‐phenylphthalimide ( 5a ) and acrylonitrile ( 2a ) under Zn‐NH 3 conditions (Table 4, entry 1).…”

Section: Resultsmentioning

confidence: 99%

“…Following the previously reported intramolecular coupling of phthalimides with α,β‐unsaturated esters by an electroreductive system11 or SmI 2 chemistry,12 we envisaged that these Zn‐NH 3 conditions could provide an opportunity to achieve the intramolecular reductive coupling reaction (Scheme ). To examine this, we first applied the standard reaction conditions (as described in Table 5) to phthalimide 5k .…”

Section: Resultsmentioning

confidence: 99%

“…For the synthesis of 3‐hydroxyisoindolin‐1‐ones8 and 3‐hydroxyoxindoles,9,10 several strategies have been reported. However, the reductive coupling of phthalimides with activated alkenes to afford 3‐hydroxyisoindolin‐1‐one derivatives is only scarcely mentioned in literature, with examples such as the intra‐ and intermolecular reductive coupling of phthalimides with activated alkenes via an electroreductive method11 or samarium(II) iodide (SmI 2 ) chemistry 12. Moreover, to the best of our knowledge, the synthesis of 3,3‐disubstituted phthalides and 3‐hydroxyoxindole derivatives via ene‐carbonyl reductive coupling has never been reported.…”

Section: Introductionmentioning

confidence: 99%

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Ene‐Carbonyl Reductive Coupling for the Synthesis of 3,3‐Disubstituted Phthalide, 3‐Hydroxyisoindolin‐1‐one and 3‐Hydroxyoxindole Derivatives

et al. 2014

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An efficient method for the synthesis of three classes of heterocyclic derivatives such as 3,3disubstituted phthalides, 3-hydroxyisoindolin-1-ones and 3-hydroxyoxindoles, is reported. In the presence of the simple reductive system, zinc (Zn)/ammonia (NH 3 ) [or zinc-copper (Zn-Cu)/ammonia], a wide range of alkenes including acrylates, acrylonitrile, acrylamide and vinyl sulfoxide underwent reductive coupling with methyl 2-acylbenzoates and subsequent lactonization to provide 3,3-disubstituted phthalides in good to high yields at ambient temperature. In a similar manner, 3-hydroxyisoindolin-1one and 3-hydroxyoxindole derivatives could also be easily prepared by direct reductive coupling of phthalimides and N-substituted isatins with activated alkenes, respectively. Application of this methodology towards the synthesis of 1-naphthol derivatives on a gram scale is also depicted. Furthermore, the intramolecular phthalimides-ene reductive coupling afforded the respective cyclization products with high diastereoselectivity.Scheme 1. Optimization studies for the reductive coupling of methyl 2-benzoylbenzoate (1a) with acrylamide (2e).Scheme 2. Reductive couplings of 1l with 2b, 1m with 2c and 1a with 4. Scheme 4. Dieckmann condensation to afford a 1-naphthol derivative.Scheme 5. Oxidative removal of the N-a-methyl-4-methoxybenzyl group. 838

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Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Ene‐Carbonyl Reductive Coupling for the Synthesis of 3,3‐Disubstituted Phthalide, 3‐Hydroxyisoindolin‐1‐one and 3‐Hydroxyoxindole Derivatives

et al. 2014

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“…The successful construction of nitrogen heterocycles via aminoketyl radicals depends on the capacity of the Sm(II) reagent to generate and stabilize the formed radical to prevent reduction to the anion. In an alternative mechanism, Chiara reported the SmI 2 -mediated reductive cross-coupling between phthalimides and activated olefins, nitrones, and oxime ethers ( Scheme 6 ) [ 40 ]. The reaction affords α-hydroxy lactams in high yields and with generally good stereoselectivity.…”

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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“…Recently, Li et al used the same palladium catalyst for the cyclization with phenylglyoxylic acids [23]. Other methods for obtaining isoindolinone alcohols include fluoride-catalyzed nucleophilic additions [24,25], reductive couplings with aldehydes, ketones and olefins [26][27][28][29], and photodecarboxylative additions of carboxylates to phthalimides [30,31].…”

Section: Introductionmentioning

confidence: 99%

Synthesis of 3–aryl 3–hydroxyisoindolinones by the Addition of Grignard and Organolithium Reagents to Phthalimides

Glavač

Dokli

Gredičak

2017

COC

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Background: The 3-substituted 3-hydroxyisoindolinone motif is common to a variety of compounds with potent biological activities. In recent years, they have also been increasingly used as substrates in various asymmetric transformations. Current methods for their preparation either do not tolerate wide range of functional groups, or yield 3-hydroxyisoindolinones as N-substituted products, which makes them inapplicable as substrates for the asymmetric transformations.Objective: Aim of this study was a detailed examination of the synthesis of 3-substituted 3hydroxyisoindolinones comprising various functional groups and unsubstituted phthalimide nitrogen.Method: Grignard and organolithium reagents were employed as nucleophiles for the synthesis of 3substituted 3-hydroxyisoindolinones under various reaction conditions. Results: Phenyl substituents with electron donating groups are easily introduced by employing a Grignard reaction, while electron-poor arenes require a lithium exchange or direct lithiation strategy. The protocols are tolerant of various functional groups on the nucleophile, and a wide range of 3-hydroxyisoindolinones were afforded in good to excellent yields. Conclusion:Simple and inexpensive method for the synthesis of 3-substituted 3-hydroxyisoindolinone has been developed. By tweaking the reaction conditions, described protocols are tolerant of a wide range of functional groups, and yield 3-substituted isoindolinone alcohols with unsubstituted phthalimide nitrogen.

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Phthalimides as Exceptionally Efficient Single Electron Transfer Acceptors in Reductive Coupling Reactions Promoted by Samarium Diiodide

Cited by 29 publications

References 24 publications

Ene‐Carbonyl Reductive Coupling for the Synthesis of 3,3‐Disubstituted Phthalide, 3‐Hydroxyisoindolin‐1‐one and 3‐Hydroxyoxindole Derivatives

Ene‐Carbonyl Reductive Coupling for the Synthesis of 3,3‐Disubstituted Phthalide, 3‐Hydroxyisoindolin‐1‐one and 3‐Hydroxyoxindole Derivatives

Synthesis of Nitrogen Heterocycles Using Samarium(II) Iodide

Synthesis of 3–aryl 3–hydroxyisoindolinones by the Addition of Grignard and Organolithium Reagents to Phthalimides

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