Synthesis of NH-sulfoximines from sulfides by chemoselective one-pot N- and O-transfers

Tota, Arianna; Zenzola, Marina; Chawner, Stephen John; John‐Campbell, Sahra St; Carlucci, Claudia; Romanazzi, Giuseppe; Degennaro, Leonardo; Bull, James A.; Luisi, Renzo

doi:10.1039/c6cc08891k

Cited by 160 publications

(138 citation statements)

References 42 publications

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“…Under standard S ‐alkylation conditions, the reaction of thiophenol ( 7 a ) with commercial 1‐bromo‐3‐chloropropane ( 8 a ) in the presence of triethylamine gave thioether 9 ab in 78 % yield. One‐pot sulfoximine formation with (diacetoxyiodo)benzene and ammonium carbamate in methanol afforded acyclic sulfoximine 10 ab in a clean reaction with no sign of cyclized product 3 ab , as indicated by TLC and UPLC‐MS analysis. However, initial attempts to isolate 10 ab by preparative HPLC resulted in a mixture of acyclic sulfoximine 10 ab and cyclized 3 ab in about 2:1 ratio.…”

Section: Resultsmentioning

confidence: 87%

Increasing Complexity: A Practical Synthetic Approach to Three‐Dimensional, Cyclic Sulfoximines and First Insights into Their in Vitro Properties

Boulard

Zibulski

Oertel

et al. 2020

Chemistry A European J

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A short synthetic approach with broad scope to access five‐ to seven‐membered cyclic sulfoximines in only two to three steps from readily available thiophenols is reported. Thus, simple building blocks were converted to complex molecular structures by a sequence of S‐alkylation and one‐pot sulfoximine formation, followed by intramolecular cyclization. Seventeen structurally diverse cyclic sulfoximines were prepared in high overall yields. In vitro evaluation of these underrepresented, three‐dimensional, cyclic sulfoximines with respect to properties relevant to medicinal chemistry did not reveal any intrinsic flaw for application in drug discovery.

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Section: Resultsmentioning

confidence: 87%

Increasing Complexity: A Practical Synthetic Approach to Three‐Dimensional, Cyclic Sulfoximines and First Insights into Their in Vitro Properties

Boulard

Zibulski

Oertel

et al. 2020

Chemistry A European J

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“…In order to investigate whether replacing the sulfone moiety with a sulfoximine improves the antiplasmodial activity of the thiochroman scaffolds, sulfoximines 6a and 6b were prepared as shown in Scheme 1 using the protocol reported by Zenzola et al [30,31] our previously reported protocol, [32] was oxidized using 1.2 equiv. of oxone ® to afford sulfoxides 8a and 8b as a separable mixture in 1:3 diastereoisomeric ratio, while oxidation with excess oxone ® led to the formation of sulfone 5 in reasonable yields (Scheme 1).…”

Section: Synthesis Of Sulfoximine Analogues Of the Sulfone-derived mentioning

confidence: 99%

Design, synthesis, and antiplasmodial evaluation of a series of novel sulfoximine analogues of carbohydrate‐based thiochromans

et al. 2018

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Sulfone/sulfoxide-containing carbohydrate derived thiochromans were found to be highly active antiplasmodial agents. However, the inability of the sulfone/sulfoxide functional groups for further derivatization and manipulation limited the potential for further exploration. In this study, based on the interesting and important physicochemical properties, as well as amenability of sulfoximines (isosters of sulfones) for further derivatization, a series of novel sulfoximine-type carbohydrate-derived thiochroman derivatives have been successfully synthesized, characterized, and evaluated for their antiplasmodial activity. Although the replacement of the sulfone functional group with a sulfoximine unit improved the antiplasmodial activity of the scaffolds, the activity was highly dependent on the configuration of the stereogenic centre at the sulfur atom. Moreover, analysis of the crystal structures of the sulfoximine analogues revealed that the bond between the sulfur and nitrogen atoms of the sulfoximine functional group is not a true double bond but rather a polarized single bond. K E Y W O R D Santimalarial, antiplasmodial, sulfoximine, thiochroman

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“…[14] The NH transfer occurred with sources of ammonia, with ammonium carbamate preferred, in the presence of bis-(acetoxy)iodobenzene as the oxidant. [16][17][18] Herein, we report the development of an ew strategy for the direct synthesis of NH-sulfonimidamides from sulfenamides as simple,r eadily available,a nd previously unexplored substrates.Ahighly selective one-pot NH and O transfer is achieved using operationally simple conditions. [15] We,a nd others, recently reported related conditions for the conversion of sulfides into sulfoximines in ao ne-pot process through ahighly chemoselective NH and Ot ransfer.…”

Section: Introductionmentioning

confidence: 99%

Synthesis of Sulfonimidamides from Sulfenamides via an Alkoxy‐amino‐λ⁶‐sulfanenitrile Intermediate

et al. 2019

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Sulfonimidamides are intriguing new motifs for medicinal and agrochemistry,a nd provide attractive bioisosteres for sulfonamides.However,there remain few operationally simple methods for their preparation. Here,t he synthesis of NH-sulfonimidamides is achieved directly from sulfenamides,themselves readily formed in one step from amines and disulfides.Ahighly chemoselective and one-pot NH and O transfer is developed, mediated by PhIO in iPrOH, using ammonium carbamate as the NH source,and in the presence of 1equivalent of acetic acid. Awide range of functional groups are tolerated under the developed reaction conditions,w hich also enables the functionalization of the antidepressants desipramine and fluoxetine and the preparation of an aza analogue of the drug probenecid. The reaction is shown to proceed via different and concurrent mechanistic pathways, including the formation of novel SNsulfanenitrile species as intermediates.Several alkoxy-amino-l 6 -sulfanenitriles are prepared with different alcohols,a nd shown to be alkylating agents to arange of nucleophiles. Scheme 1. Potential bioisosteres for sulfones and sulfonamides, examples of bioactive sulfonimidamides, and current strategies for the synthesis of sulfonimidamides.

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Synthesis of NH-sulfoximines from sulfides by chemoselective one-pot N- and O-transfers

Abstract: Sulfoximines have recently emerged as interesting motifs for both medicinal and synthetic chemists.

Cited by 160 publications

References 42 publications

Increasing Complexity: A Practical Synthetic Approach to Three‐Dimensional, Cyclic Sulfoximines and First Insights into Their in Vitro Properties

Increasing Complexity: A Practical Synthetic Approach to Three‐Dimensional, Cyclic Sulfoximines and First Insights into Their in Vitro Properties

Design, synthesis, and antiplasmodial evaluation of a series of novel sulfoximine analogues of carbohydrate‐based thiochromans

Synthesis of Sulfonimidamides from Sulfenamides via an Alkoxy‐amino‐λ⁶‐sulfanenitrile Intermediate

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Synthesis of NH-sulfoximines from sulfides by chemoselective one-pot N- and O-transfers

Abstract: Sulfoximines have recently emerged as interesting motifs for both medicinal and synthetic chemists.

Cited by 160 publications

References 42 publications

Increasing Complexity: A Practical Synthetic Approach to Three‐Dimensional, Cyclic Sulfoximines and First Insights into Their in Vitro Properties

Increasing Complexity: A Practical Synthetic Approach to Three‐Dimensional, Cyclic Sulfoximines and First Insights into Their in Vitro Properties

Design, synthesis, and antiplasmodial evaluation of a series of novel sulfoximine analogues of carbohydrate‐based thiochromans

Synthesis of Sulfonimidamides from Sulfenamides via an Alkoxy‐amino‐λ6‐sulfanenitrile Intermediate

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Synthesis of Sulfonimidamides from Sulfenamides via an Alkoxy‐amino‐λ⁶‐sulfanenitrile Intermediate