A Striking Case of Enantioinversion in Gold Catalysis and Its Probable Origins

Ilg, Marina K.; Wolf, Lawrence M.; Mantilli, Luca; Farès, Christophe; Thiel, Walter; Fürstner, Alois

doi:10.1002/chem.201502160

Cited by 36 publications

(21 citation statements)

References 63 publications

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“…However, some previous studies demonstrated through kinetic analyses and calculations that the origin of solvent‐dependent stereodiscrimination was often controlled by an enthalpy–entropy compensation . Regarding gold‐catalysed enantiodivergent reactions, solvent, temperature or counterion proved to induce the enantioinversion alone or in combination with one another . Herein, we report the first silver‐ and solvent‐dependent enantiodivergent gold(I)‐catalysed reaction.…”

Section: Introductionmentioning

confidence: 99%

Gold(I)‐Catalysed Asymmetric Hydroamination of Alkenes: A Silver‐ and Solvent‐Dependent Enantiodivergent Reaction

Abadie

Trivelli

Medina

et al. 2017

Chemistry A European J

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In the present study, we report the first silver-dependent enantiodivergent gold-catalysed reaction. The asymmetric intramolecular hydroamination of alkenes catalysed by the combination of a single chiral binuclear gold(I) chloride complex and silver perchlorate can afford both enantiomers of the products by a simple solvent change from toluene to methanol. Such an enantiodivergent reaction is strictly independent of the reaction temperature or of the nature of the catalyst anion and displays the same first-order kinetic rate law with respect to substrate concentration in both solvents. Beyond a simple solvent effect the enantioinversion is controlled by gold-silver chloride adducts which occur only in methanol and allow a dual activation of the reagent. While one single gold atom activates the alkene moiety, the other gold atom forms an oxophilic gold-silver chloride adduct which is likely to interact with the carbamate function. By comparison with toluene, which affords (S)-enantiomer, this proximal and bimetallic activation would allow an opposite stereodifferentiation of the two diastereomeric intermediates during the final protodeauration step and lead therefore to the (R)-enantiomer.

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Section: Introductionmentioning

confidence: 99%

Gold(I)‐Catalysed Asymmetric Hydroamination of Alkenes: A Silver‐ and Solvent‐Dependent Enantiodivergent Reaction

Abadie

Trivelli

Medina

et al. 2017

Chemistry A European J

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“…[30] Based on this rationale,w es tarted to screen chiral gold complexes with the hope of finding am atching substrate/ catalyst pair. [31,32] In fact, the cationic species derived from the dinuclear Biphep complex (R)-39 and 2A gSbF 6 [33] was not only able to overcome the inertia of the substrate but provided the desired enol acetate 34 in aw ell reproducible yield of no less than 91 %. This excellent outcome met our expectation that the gold catalyzed [3,3]-sigmatropic rearrangement should be faster than the attack of the C11ÀOH group onto the resulting allenyl acetate of type B across the macrocyclic perimeter (Scheme 5).…”

Section: Methodsmentioning

confidence: 99%

Concise Total Synthesis of Enigmazole A

et al. 2015

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An efficient entry into the phosphorylated marine macrolide enigmazoleAis described. Enigmazole Ainterferes with c-Kit signaling by an as yet unknown mode of action and is therefore ap otential lead in the quest for novel anticancer agents.K ey to success is ag old-catalyzed cascade comprising a[3,3]-sigmatropic rearrangement of apropargyl acetate along the periphery of am acrocyclic scaffold, followed by at ransannular hydroalkoxylation of the resulting transient allenyl acetate.This transformation mandated the use of achiral gold catalyst to ensure amatching double-asymmetric setting.Other noteworthy steps are the preparation of the oxazole building blockbyapalladium-catalyzed CÀHactivation, as well as the smooth ring-closing alkyne metathesis of ad iyne substrate bearing ap ropargylic leaving group,w hichh as only little precedent.

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“…The acyclic TADDOL‐based phosphoramidite–gold complex [{( S , S , S ,S)‐ L19 }AuCl], with 2‐naphthalenyl substituents, developed by Fürstner and co‐workers showed excellent performance in the intramolecular hydroalkoxylation of γ‐hydroxy allene and converted 156 a into the corresponding annulation product 157 a in high yield (93 %) with excellent enantioselectivity (96 % ee ; Scheme ) . Somewhat surprisingly, the best result was obtained in EtOH as the solvent, which did not outperform the attack of the tethered hydroxy group onto the allene moiety.…”

Section: Cyclization Of C−c Multiple Bonds With Tethered Nucleophilesmentioning

confidence: 99%

Gold‐Catalyzed Enantioselective Annulations

Zhang

2016

Chemistry A European J

221

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Non-oxidative,regioselective,and convergent access to densely functionalized oxazoles is realized in af unctional-group 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 sub-strates:i np-acid catalysis their donor nature aids metal-alkyne coordination and affords highly polarized electro-philes,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 onor-nitrogen 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 ketenethio-nium 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 on-trolling 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 ...

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A Striking Case of Enantioinversion in Gold Catalysis and Its Probable Origins

Cited by 36 publications

References 63 publications

Gold(I)‐Catalysed Asymmetric Hydroamination of Alkenes: A Silver‐ and Solvent‐Dependent Enantiodivergent Reaction

Gold(I)‐Catalysed Asymmetric Hydroamination of Alkenes: A Silver‐ and Solvent‐Dependent Enantiodivergent Reaction

Concise Total Synthesis of Enigmazole A

Gold‐Catalyzed Enantioselective Annulations

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