Secondary Deuterium Isotope Effect in an Electrophilic Aromatic Substitution ‐ Protodesilylation of Trimethylphenylsilane

Szele, Ivanka

doi:10.1002/hlca.19810640833

Cited by 14 publications

(4 citation statements)

References 29 publications

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“…Protodesilylation of arylsilanes exhibits an inverse β-SKIE, typical for an S E Ar reaction with rate-limiting formation of a WI. The absence of a SKIE in intermolecular competition between d 0 -/2,6- d 2 -arylsilanes (Chart ) suggests that there is little rehybridization β to Si, and the absence of a normal SKIE for arylation of 2-bromothiophene 3 with the CH 3 /CD 3 isotopologues of tolyltrimethylsilanes implies that there is little delocalization of charge onto the aromatic system during the product-determining step of C–Si auration .…”

Section: Results and Discussionmentioning

confidence: 99%

Gold-Catalyzed Oxidative Coupling of Arylsilanes and Arenes: Origin of Selectivity and Improved Precatalyst

2013

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The mechanism of gold-catalyzed coupling of arenes with aryltrimethylsilanes has been investigated, employing an improved precatalyst (thtAuBr3) to facilitate kinetic analysis. In combination with linear free-energy relationships, kinetic isotope effects, and stoichiometric experiments, the data support a mechanism involving an Au(I)/Au(III) redox cycle in which sequential electrophilic aromatic substitution of the arylsilane and the arene by Au(III) precedes product-forming reductive elimination and subsequent cycle-closing reoxidation of the metal. Despite the fundamental mechanistic similarities between the two auration events, high selectivity is observed for heterocoupling (C-Si then C-H auration) over homocoupling of either the arylsilane or the arene (C-Si then C-Si, or C-H then C-H auration); this chemoselectivity originates from differences in the product-determining elementary steps of each electrophilic substitution. The turnover-limiting step of the reaction involves associative substitution en route to an arene π-complex. The ramifications of this insight for implementation of the methodology are discussed.

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Section: Results and Discussionmentioning

confidence: 99%

Gold-Catalyzed Oxidative Coupling of Arylsilanes and Arenes: Origin of Selectivity and Improved Precatalyst

2013

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“…In control reactions CatBBr did not react with PhSiMe 3 , in contrast to the more Lewis acidic BBr 3 . , PhSiMe 3 can be used as an additive to accelerate arene borylation; catalysis with equimolar CatBBr and PhSiMe 3 (at 5 mol % [Et 3 Si][CbBr 6 ] loading) in toluene resulted in slow, but catalytic, arene borylation at 25 °C and relatively rapid borylation at 100 °C (entry 10). The Bro̷nsted acidic byproduct from electrophilic borylation protodesilates PhSiMe 3 , presumably generating the reactive silylium cation [Me 3 Si][CbBr 6 ], which closes the cycle by reaction with CatBBr. This circumvented the rate-limiting protonation of CatBH, but led to mixed arene products due to the competing borylation of PhSiMe 3 and toluene by the reactive [CatB][CbBr 6 ] species.…”

Section: Resultsmentioning

confidence: 99%

Chelate Restrained Boron Cations for Intermolecular Electrophilic Arene Borylation

Grosso¹,

Pritchard²,

et al. 2009

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Highly electrophilic boron species that borylate arenes are generated by halide abstraction from CatBX (Cat = catecholato, C 6 H 4 O 2 2-, X = Cl or Br) by [Et 3 Si][CbBr 6 ] (CbBr 6 = [closo-1-H-CB 11 H 5 Br 6 ] -). A transient [CatB][CbBr 6 ] related species reacts as a synthetic equivalent of [CatB] þ in intermolecular electrophilic borylation, with reactions proceeding rapidly at 25°C. The [CatB] þ moiety was shown to be strongly Lewis acidic on the basis of 1 H and 31 P{ 1 H} NMR spectroscopy of the crotonaldehyde and triethylphosphine oxide adducts, respectively. Catalytic quantities of [Et 3 Si][CbBr 6 ] and CatBX were effective for the high-yielding borylation of arenes by CatBH in a highly atom efficient cycle with H 2 the only byproduct. Successful catalysis was dependent on the robust [CbBr 6 ] -anion and the use of electrophile-resistant borane sources.

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“…It is noteworthy that no allylation in the α-position of the keto group took place. Upon heating, allyl ether 13 smoothly underwent Claisen rearrangement with migration of the allyl group to the only vacant ortho-position affording 2-(N,N-diethylcarboxamide)-4-allylestrone (14) in 77% yield (Scheme 5).…”

Section: O Netmentioning

confidence: 99%

“…This thermal 1,3-migration of the trimethylsilyl group 13 can be considered as a protodesilylation 14 promoted by the acidic phenolic proton and trapping of the cleaved silyl species by the phenolate anion. O-Silylated estrone ketal 20 was prepared also directly through the silylation of estrone ketal with trimethylchlorosilane.…”

Section: Scheme 7 Thermal C → O Migration Of Trimethylsilyl Groupmentioning

confidence: 99%

Synthetic Approaches towards 4-Functionalized Estrone Derivatives

et al. 2012

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Directed ortho-lithiation of estrone carbamate followed by reaction with electrophiles afforded 2-substituted estrone derivatives. Reductive cleavage of the carbamate group followed by Oallylation and Claisen rearrangement led to new 4-functionalized estrone derivatives.Steroids are a biologically important class of natural compounds with a large range of pharmaceutical applications. 1,2 Specific functionalization of the tetracyclic core is still a key synthetic issue and current methods have been reviewed. [3][4][5] Steroidal derivatives exert a wide range of biological actions. These include receptor agonists or antagonists of estrogens, androgens, corticoids, and inhibitors of steroidogenic enzymes. 6,7 Besides manual chemistry, combinatorial methods have also been pursued to generate compound libraries. 8As part of an ongoing research program we were interested in synthesizing new estrone derivatives functionalized at C-4. However, synthesis of these estrones is still not well explored. A common approach utilizes the Claisen rearrangement of estrone allyl ether (2). 9 The published results show that this method creates mixtures of 2-allyl-(3) and 4-allylestrone (4) (Scheme 1).Scheme 1 Claisen rearrangement of estrone allyl ether (2) In this report we disclose our investigations on the selective synthesis of 4-substituted estrone derivatives by exploiting the ortho-directed lithiation of estrone carbamate 5. 10 For realizing this approach a robust protection of the 17-keto group was required, which we found to be the acetal functionality. Estrone (1) was protected under standard conditions and the resulting acetal was treated with diethylcarbamoyl chloride in pyridine in the presence of triethylamine. The desired carbamate 5 was obtained in 84% overall yield (Scheme 2). It is noteworthy that carbamoylation proceeded slowly without completion in the absence of triethylamine. Scheme 2 Preparation of esterone 3-(N,N-diethyl)carbamate 5Treatment of carbamate 5 with sec-butyllithium in the presence of TMEDA (THF, -78°C, 1 h) followed by trapping of the carbanion with electrophiles such as methyl iodide or trimethylsilyl chloride afforded the corresponding estrone derivatives 6 and its 4-isomer 7 (ratio = 10:1) as well as 10 in synthetically useful yields (Scheme 3). Clearly, substitution at C-2 is favored over functionalization at C-4, reflecting the preferred site of lithiation. It can be assumed that this preference is based on sterical grounds. The regioselectivity of ortho-lithiation observed for carbamate 5 correlates well with the results reported for ortho-metalation of estrone derivatives with the 3-methoxymethyl substituent as directing group. 11 The methyl-substituted carbamates 6 and 7 could smoothly be deprotected for liberating the keto group at C-17 yielding estrone derivatives 8 and 9. In a similar manner, the 2-position can exclusively be functionalized as amide, when the lithiated intermediate was reacted with diethylcarbamoyl chloride. Hydrolysis of the acetal group yielded estrone derivative ...

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Secondary Deuterium Isotope Effect in an Electrophilic Aromatic Substitution ‐ Protodesilylation of Trimethylphenylsilane

Cited by 14 publications

References 29 publications

Gold-Catalyzed Oxidative Coupling of Arylsilanes and Arenes: Origin of Selectivity and Improved Precatalyst

Gold-Catalyzed Oxidative Coupling of Arylsilanes and Arenes: Origin of Selectivity and Improved Precatalyst

Chelate Restrained Boron Cations for Intermolecular Electrophilic Arene Borylation

Synthetic Approaches towards 4-Functionalized Estrone Derivatives

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