Additions to <i>N</i>‐Sulfinylamines as an Approach for the Metal‐free Synthesis of Sulfonimidamides: <i>O</i>‐Benzotriazolyl Sulfonimidates as Activated Intermediates

Bremerich, Maximilian; Conrads, Christian; Langletz, Tim; Bolm, Carsten

doi:10.1002/ange.201911075

Cited by 19 publications

(4 citation statements)

References 66 publications

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“…In an alternative approach, we reported a one-pot, multistep, synthesis of sulfonimidamides from the sulfinylamine reagent N -sulfinyltritylamine (TrNSO), organometallic reagents, and amines, albeit with the requirement of an intermediate oxidative step ( Scheme 1 , eq 1). 19 , 20 The scope of this reaction proved to be broad, and it has now found use in pharmaceutical companies, 21 leading to TrNSO being commercially available. More recently we described a second sulfinylamine reagent, this time featuring a tert -alkyl substituent ( t -Oct-NSO), and used this reagent to prepare sulfilimines, en route to sulfondiimines.…”

Section: Introductionmentioning

confidence: 99%

Harnessing Sulfinyl Nitrenes: A Unified One-Pot Synthesis of Sulfoximines and Sulfonimidamides

et al. 2020

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Sulfoximines and sulfonimidamides are promising compounds for medicinal and agrochemistry. As monoaza analogues of sulfones and sulfonamides, respectively, they combine good physicochemical properties, high stability, and the ability to build complexity from a three-dimensional core. However, a lack of quick and efficient methods to prepare these compounds has hindered their uptake in molecule discovery programmes. Herein, we describe a unified, one-pot approach to both sulfoximines and sulfonimidamides, which exploits the high electrophilicity of sulfinyl nitrenes. We generate these rare reactive intermediates from a novel sulfinylhydroxylamine (R–O–N=S=O) reagent through an N–O bond fragmentation process. Combining sulfinyl nitrenes with carbon and nitrogen nucleophiles enables the synthesis of sulfoximines and sulfonimidamides in a reaction time of just 15 min. Alkyl, (hetero)aryl, and alkenyl organometallic reagents can all be used as the first or second component in the reaction, while primary and secondary amines, and anilines, all react with high efficiency as the second nucleophile. The tolerance of the reaction to steric and electronic factors has allowed for the synthesis of the most diverse set of sulfoximines and sulfonimidamides yet described. Experimental and computational investigations support the intermediacy of sulfinyl nitrenes, with nitrene formation proceeding via a transient triplet intermediate before reaching a planar singlet species.

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Section: Introductionmentioning

confidence: 99%

Harnessing Sulfinyl Nitrenes: A Unified One-Pot Synthesis of Sulfoximines and Sulfonimidamides

et al. 2020

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“…3 The growth in use of sulfonimidamides has been mirrored by recent innovations 4 in their synthesis. 5 Approaches that employ sulfonimidoyl halides, 6 or sulfonimidates, 7 have been used extensively; however, access to these substrates can be challenging. The imination, or imination/oxidation, of lower oxidation-state precursors have emerged as useful methods to access sulfonimidamides.…”

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confidence: 99%

A Silyl Sulfinylamine Reagent Enables the Modular Synthesis of Sulfonimidamides via Primary Sulfinamides

et al. 2022

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A new N -silyl sulfinylamine reagent allows the rapid preparation of a broad range of (hetero)aryl, alkenyl, and alkyl primary sulfinamides, using Grignard, organolithium, or organozinc reagents to introduce the carbon fragment. Treatment of these primary sulfinamides with an amine in the presence of a hypervalent iodine reagent leads directly to NH-sulfonimidamides. This two-step sequence is straightforward to perform and provides a modular approach to sulfonimidamides, allowing ready variation of both reaction components, including primary and secondary amines.

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“…12,[17][18][19] While these aza-S(VI) derivatives serve as pharmacological modulators, the increased hydrolytic stability and structural variability of sulfonimidoyl fluorides relative to sulfonyl fluorides is promising for future chemical probe development. 20 The biological significance of sulfoximines and sulfonimidamides has resulted in myriad methods for their racemic syntheses via oxidative iminations of S(II) and S(IV) centers, [21][22][23] S(VI) functional group interconversions, [24][25][26] and reagent-based approaches; [27][28][29][30][31][32] conversely, few asymmetric methods currently exist. 33 In comparison, the preparation of sulfonimidoyl fluorides is much more limited.…”

Section: Introductionmentioning

confidence: 99%

Asymmetric synthesis of sulfoximines, sulfonimidoyl fluorides and sulfonimidamides enabled by an enantiopure bifunctional S(VI) reagent

Teng,

Shultz,

Shan

et al. 2024

Nat. Chem.

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An increased interest to expand three-dimensional chemical space for the design of new materials and medicines has created a demand for isosteric replacement groups of commonly used molecular functionality. The structural and chemical properties of chiral S(VI) functional groups provide unique spatial and electronic features compared to their achiral sulfur-and carbon-based counterparts. Manipulation of the S(VI) center to introduce structural variation with stereochemical control has remained a synthetic challenge. The stability of sulfonimidoyl fluorides and the efficiency of sulfur fluorine exchange (SuFEx) chemistry has enabled the development of an enantiopure bifunctional S(VI) transfer reagent (t-BuSF) to overcome current synthetic limitations. Here, this reagent platform serves as a chiral SuFEx template for the rapid asymmetric synthesis of over seventy different sulfoximines, sulfonimidoyl fluorides and sulfonimidamides with excellent enantiopurity and good overall yields. Furthermore, the practical utility of t-BuSF was demonstrated in the syntheses of enantiopure pharmaceutical intermediates and analogs.

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Additions to N‐Sulfinylamines as an Approach for the Metal‐free Synthesis of Sulfonimidamides: O‐Benzotriazolyl Sulfonimidates as Activated Intermediates

Cited by 19 publications

References 66 publications

Harnessing Sulfinyl Nitrenes: A Unified One-Pot Synthesis of Sulfoximines and Sulfonimidamides

Harnessing Sulfinyl Nitrenes: A Unified One-Pot Synthesis of Sulfoximines and Sulfonimidamides

A Silyl Sulfinylamine Reagent Enables the Modular Synthesis of Sulfonimidamides via Primary Sulfinamides

Asymmetric synthesis of sulfoximines, sulfonimidoyl fluorides and sulfonimidamides enabled by an enantiopure bifunctional S(VI) reagent

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