Alkynyl Thioethers in Gold‐Catalyzed Annulations To Form Oxazoles

Reddy, Raju Jannapu; Ball‐Jones, Matthew P.; Davies, Paul W.

doi:10.1002/anie.201706850

Cited by 95 publications

(53 citation statements)

References 70 publications

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“…[19,20] X-ray diffraction subsequently confirmed the structures of 3aa and 3ga (see the Supporting Information). [21] These first nickel-mediated Kumada-type couplings with 5-thioether oxazoles [22] demonstrate the value of the thioether handle,i nt his case providing substitution patterns which are not directly accessible from the annulation (see 4b in Table 1).…”

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Alkynyl Thioethers in Gold‐Catalyzed Annulations To Form Oxazoles

2017

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Non-oxidative,regioselective,and convergent access to densely functionalized oxazoles is realized in af unctionalgroup tolerant manner using alkynyl thioethers.S ulfur-terminated alkynes provideaccess to reactivity previously requiring strong donor-substituted alkynes such as ynamides.Sulfur does not act in an analogous donor fashion in this gold-catalyzed reaction, thus leading to complementary regioselective outcomes and addressing the limitations of using ynamides.Compared to other heteroatom-substituted alkynes,alkynyl thioethers are remarkably little explored in intermolecular late-transition-metal catalysis,d espite being readily accessed and robust. [1,2] Ynamides,i nc ontrast, are privileged substrates:i np-acid catalysis their donor nature aids metalalkyne coordination and affords highly polarized electrophiles,t hus providing the high chemo-and regioselectivity required for the discovery of efficient intermolecular reactions (Scheme 1a). [3,4] As the resulting inclusion of ad onornitrogen atom limits the utility of the products,r etaining the reactivity profile of these transformations whilst accessing more flexible and readily elaborated substitution patterns would be desirable.T he value of sulfur-substituted compounds [5] coupled with progress in C À Ca nd C-heteroatom bond formation from CÀSbonds, [6] renders alkynyl thioethers appealing alternatives to ynamides.I ndeed the ketenethionium pathway (Scheme 1a)f rom alkynyl thioethers has recently been invoked in proton-catalyzed reactions with nitriles [2g,h] and gold-catalyzed reactions with sulfides.[2i]Ynamides enabled the discovery of formal [3+ +2] dipolar cycloadditions with nucleophilic nitrenoids, [7] thus allowing intermolecular access to a-imino gold carbene-type reactivity for heterocycle synthesis (Scheme 1b). [8, 9] Such reactions, which do not depend on ynamides,a re scarce.[8b,h] As trong donor alkyne substituent proved critical in the formation of oxazoles using N-acyl pyridinium N-aminides,aselectron-rich alkynes such as anisole derivatives did not react (Scheme 1b, inset). [8a,b] Oxazoles are valuable synthetic intermediates [10,11] and structural components in bioactive natural products, [12] agrochemicals, [13] ligands, [14] and functional materials.[15]Despite recent advances,asingle modular and convergent route to trisubstituted oxazoles,which provides the structural and functional-group diversity needed across the 2-, 4-, and 5-positions,r emains unrealized. [16] Following our interest in the use of gold catalysis with sulfides [17] we report here on the reactivity of alkynyl thioethers with nucleophilic nitrenoids to prepare oxazoles. Importantly,t he regioselectivity is not consistent with ac ontrolling ketenethionium species.T he sulfur group plays an alternative role in enabling reactivity,t hus proving complementary to donor-enabled approaches.Ther eaction of the alkynyl thioether 1a and aminide 2a (Table 1) showed that conversion into the oxazole 3 was possible at 125 8 8Ci n1 ,2-dichlorobenzene (1,2-DCB;s ee...

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“…Thea lkynyl thioether 1j gave 5thioethers 3ja/c as the major isomers,t hus providing 4-alkyl oxazoles.S terically-congested bi(hetero)aryl linkages may also be formed as single regioisomers (3lc). [21]…”

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Alkynyl Thioethers in Gold‐Catalyzed Annulations To Form Oxazoles

2017

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“…The reactivity‐enhancing effect of a sulfenyl substituent could be explained by sulfur‐gold interactions stabilising the polarised gold keteneiminium contribution B’ to generate a more effective electrophile (Scheme ). Sulfur‐gold interactions could also conceivably help to favour productive gold‐ynamide coordination over unproductive interaction with nitrenoid . Invoking a stabilising dative or hyperconjugative interaction between the gold and sulfur can explain the lower reactivity observed with S ‐phenyl ynamide 18 b over S ‐methyl ynamide 18 a .…”

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confidence: 99%

Sulfenyl Ynamides in Gold Catalysis: Synthesis of Oxo‐functionalised 4‐aminoimidazolyl Fused Compounds by Intermolecular Annulation Reactions

2020

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Functionalised N‐heterocyclic pyridinium N‐aminides have been designed and synthesised to evaluate a nitrenoid‐based annulation strategy into imidazole‐fused oxo‐substituted frameworks of importance to medicinal and agrochemical discovery programmes. Sulfenyl substituted ynamides were identified as privileged reactants affording productive gold‐catalysed annulation reactions with these and other nitrenoids. This annulation method provides selective and efficient access into geminally amino‐sulfenyl substituted nitrogen heterocycles under mild reaction conditions.

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“…[9] Although alkynes can also generate a-imino gold carbenes by using variousn itrogen-containing nucleophiles, in most cases these a-imino carbenes are transformed into pyrroles and other azacycles through ar apid intramolecular cyclization. [10][11][12] Elaborationo fa-imino gold carbenes for other synthetic applicationsi sl ess explored. Ye and co-workers reported that a-imino gold carbenes could react with alkynes to generate vinyl cations [ Scheme 1,Eq. (2)] [12a] through ap ath distinct from that of a-oxo gold carbenes [Scheme 1, Eq.…”

Section: Introductionmentioning

confidence: 99%

Gold‐Catalyzed Annulations of N‐Propargyl Ynamides with Anthranils with Two Distinct Chemoselectivities

Hsu

Hsieh

Liu

2019

Chemistry A European J

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Gold‐catalyzed annulation of N‐propargyl ynamides with anthranils can proceed by two distinct mechanisms. In the case of a terminal N‐propargyl ynamide, its resulting α‐imino gold carbene reacts with a tethered alkyne to generate a vinyl cation to enable hydrolysis, which ultimately yields a pyrrolo[2,3‐b]quinoline derivative after treatment with p‐toluenesulfonic acid. For an internal alkyne, its α‐imino gold carbene reacts with a tethered alkyne via either a vinyl cation or an alkenylgold carbene; both paths ultimately lead to a 4‐ketone‐2‐aminopyrrole derivative. Our mechanistic analysis indicates that water is a better nucleophile than anthranil for terminal ynamides, whereas water and anthranils are equally reactive for internal ynamides.

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Alkynyl Thioethers in Gold‐Catalyzed Annulations To Form Oxazoles

Cited by 95 publications

References 70 publications

Alkynyl Thioethers in Gold‐Catalyzed Annulations To Form Oxazoles

Alkynyl Thioethers in Gold‐Catalyzed Annulations To Form Oxazoles

Sulfenyl Ynamides in Gold Catalysis: Synthesis of Oxo‐functionalised 4‐aminoimidazolyl Fused Compounds by Intermolecular Annulation Reactions

Gold‐Catalyzed Annulations of N‐Propargyl Ynamides with Anthranils with Two Distinct Chemoselectivities

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