Addition of carbon-centered radicals to imines and related compounds

Friestad, Gregory K.

doi:10.1016/s0040-4020(01)00384-2

Cited by 280 publications

(113 citation statements)

References 174 publications

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“…This behavior has only been observed for the nitro-derivative, which suggests that the electron withdrawing effect increases the electrophilicity and reactivity of the C@N bond, thereby favoring the addition of nucleophiles. Indeed, this rationalization is part of a key step to a well-known procedure in which the use of organometallic reagents facilitates the addition of different nucleophiles [57][58][59][60].…”

Section: Introductionmentioning

confidence: 99%

Penta- and heptacoordinated tin(IV) compounds derived from pyridine Schiff bases and 2-pyridine carboxylate: Synthesis and structural characterization

Ramírez‐Jiménez

Gómez

Hernández

2009

Journal of Organometallic Chemistry

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Section: Introductionmentioning

confidence: 99%

Penta- and heptacoordinated tin(IV) compounds derived from pyridine Schiff bases and 2-pyridine carboxylate: Synthesis and structural characterization

Ramírez‐Jiménez

Gómez

Hernández

2009

Journal of Organometallic Chemistry

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“…Due to the lower electron density of C=N bonds [42], hydrazones are superior radical acceptors compared to imines. So, it was thought that N-acylhydrazones could show better antioxidant activity.…”

Section: In Vitro Antioxidant Activitymentioning

confidence: 99%

Synthesis, biological evaluation and molecular docking studies of N-acylheteroaryl hydrazone derivatives as antioxidant and anti-inflammatory agents

et al. 2015

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In search of new therapeutics with greater potency, three new series of 3-methyl-1-phenyl-1H-thieno[2,3-c]pyrazole-5-carbohydrazide derivatives have been synthesized and evaluated for their in vitro antioxidant and anti-inflammatory activities. The hydrazones bearing a core pyrazole, chromone and tetrazolo[1,5-a]quinoline scaffold showed promising activities. Interestingly, compounds 3a (EC 50 = 06.00 ± 2.36) and 5c (EC 50 = 07.21 ± 0.67) showed the most potent antioxidant activity, while compounds 3a (EC 50 = 10.25 ± 1.08), 7b (EC 50 = 10.50 ± 0.99) and 7c (EC 50 = 11.18 ± 0.15) showed significant anti-inflammatory activity. Furthermore, molecular docking studies also revealed a significant correlation between the binding score and biological activity for these compounds to describe the molecular basis for the structure activity relationship (SAR) results. As these compounds are good cyclooxygenase inhibitors, isoenzyme inhibitory potency studies are warranted.

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“…To date, the lack of a catalytic asymmetric radical addition method to N-sulfonyl imines 6,7) has made the use of chiral Nsulfinyl imines as radical acceptors, for creating predictable stereodefined C-N stereogenic centers in sulfonamides, an appealing alternative synthetic strategy. Indeed, the pioneering works of Davis and Ellman on the synthesis and reactivity of N-sulfinyl imines have given the synthetic community a readily available and robust precursor of optically active amine compounds.…”

mentioning

confidence: 99%

Stereoselective Radical Addition of an Acetal to Sterically Tuned Enantiomerically Pure N-Sulfinyl Imines

Akindele

Yamada

Sejima

et al. 2010

CHEMICAL & PHARMACEUTICAL BULLETIN

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NotesGiven the ubiquitous nature of the C-N stereogenic center, efficient synthetic methods continue to be developed for its installation in both simple and complex chemical structures.1-3) These methods could be broadly classified into reactions mediated by ionic or radical species. Majority of these methods are mediated by ionic species, requiring highly basic reagents which limit the substrate scope of these approaches, albeit the products are obtained in high yield and enantioselectivity. On the other hand, methods involving radical species 4,5) are relatively under explored despite the potential of this approach to deliver much more structurally varied products using milder reagents.To date, the lack of a catalytic asymmetric radical addition method to N-sulfonyl imines 6,7) has made the use of chiral Nsulfinyl imines as radical acceptors, for creating predictable stereodefined C-N stereogenic centers in sulfonamides, an appealing alternative synthetic strategy. Indeed, the pioneering works of Davis and Ellman on the synthesis and reactivity of N-sulfinyl imines have given the synthetic community a readily available and robust precursor of optically active amine compounds. [8][9][10][11][12][13][14][15][16] Due to this rarity of radical species-mediated methods as well as our ongoing interest in radical reactions, [17][18][19] we sought to improve the efficiency and substrate scope of our initial report on radical addition of ethers and acetals to enantiopure N-p-toluenesulfinyl aldimines. 20) In this previous report, an in-house dimethylzinc-air radical initiator was used to generate carbon-centered a-alkoxyalkyl radicals from ethers and acetals. Subsequent nucleophilic addition of the radicals to the enantiopure N-sulfinyl imines followed by oxidation afforded the sulfonamide adducts in enantiomerically enriched forms. It is noteworthy that boron trifluoride diethyl etherate was essential for faster reaction rate while a sterically hindered acetal was crucial to good stereocontrol (Chart 1).Subsequent investigations have led to improved levels of stereocontrol. Herein, we detail our new findings along with a computational rationale for the improved levels of stereocontrol. Results and DiscussionAs we previously reported, 20) the reaction of (S)-Nbenzylidene-4-toluenesulfinamide (1a) with acetal 2 21) proceeded smoothly in the presence of trifluoroborane diethyl etherate using dimethylzinc-air to give a crude mixture including sulfinamide products 6a with a 9 : 1 diastereomeric ratio along with a trace amount of sulfonamide product 3a (ca. 1%). Subsequent oxidation of the crude products with m-chloroperbenzoic acid (m-CPBA) provided 3a with 80% ee in 92% yield (Table 1, entry 1). The enantiomeric ratio of 3a was the same as the diastereomeric ratio of 6a in the crude mixture, showing that no racemization took place during the m-CPBA oxidation.We reasoned that by substituting a bulkier group for the ptolyl group on the sulfur stereogenic center would presumably lead to higher levels of stereocontrol. In fac...

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Addition of carbon-centered radicals to imines and related compounds

Cited by 280 publications

References 174 publications

Penta- and heptacoordinated tin(IV) compounds derived from pyridine Schiff bases and 2-pyridine carboxylate: Synthesis and structural characterization

Penta- and heptacoordinated tin(IV) compounds derived from pyridine Schiff bases and 2-pyridine carboxylate: Synthesis and structural characterization

Synthesis, biological evaluation and molecular docking studies of N-acylheteroaryl hydrazone derivatives as antioxidant and anti-inflammatory agents

Stereoselective Radical Addition of an Acetal to Sterically Tuned Enantiomerically Pure N-Sulfinyl Imines

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