Silylation electrophilic aromatic

C-H activation at a primary benzylic site was the key step in very short syntheses of lig-nans 206 and 207 (Scheme 14.27) [138]. Even though both the substrate 203 and the vinyl-diazoacetate 204 contain very electron-rich aromatic rings, C-H activation to form 205 (43% yield and 91% ee) is still possible because the aromatic rings are sterically protected from electrophilic aromatic substitution by the carbenoid. Reduction of the ester in (S)-205 followed by global deprotection of the silyl ethers completes a highly efficient three-step asymmetric total synthesis of (-i-)-imperanene 206. Treatment of (R)-205 in a more elaborate synthetic sequence of a cascade Prins reaction/electrophilic substitution/lacto-nization results in the total synthesis of a related lignan, (-)-a-conidendrin 207. 

The first preparations of diaryliodonium salts have been reported in the 19th century, but refinements and improvements keep appearing to date. In most cases an iodoaryl species containing iodine(III) is coupled with an arene or a derivative of it in a typical electrophilic aromatic substitution. Lithiated, stannylated or silylated aryls and arylboronic acids or borates have been introduced recently in order to avoid harsh conditions and to improve yields. The iodoaryl species may be also formed in situ from arenes and iodine(III) reagents. 

Unusual orientation has been observed by Yamaguchi in electrophilic aromatic substitution using gallium trichloride. The reaction of toluene and bis-silylated 1,3-butadiyne gives an o-substituted product exclusively (Scheme 7.4), and even isopropylbenzene reacts at the o-position predominantly [15]. The tendency of the reaction to occur at the vicinity of the alkyl substituent is, however, restricted to the diyne-based electrophile for other related electrophiles derived from silylethyne, si-lylallene, or bissilylated 1,5,5,7-octatetrayne normal o/p orientation is observed. 

Lcad(rV) trifluoroacetate is a strong electrophilic and oxidizing reagent It IS a valuable reagent for the hydroxylatton of aromatic compounds [5S, 59] Lead(IV) trifluoroacetate also reacts with silylated benzenes with the exclusive formation of the corresponding trifluoroacetate esters [59] (equation 28)... 

Replacement of an aromatic/heteroaromatic proton with a trialkylsilyl group can confer a variety of synthetic advantages. The silyl moiety can mask a potentially acidic proton, and it can be readily removed by electrophiles, normally resulting in a process of ipso desilylation ... 

Lastly, Antilla has disclosed a novel asymmetric desymmetrization of a wide range of aliphatic, aromatic, and heterocyclic meso-aziridines with TMS-N3 promoted by 11 and related 12 (Scheme 5.31) [56]. Uniquely, this is one of only several reports of electrophilic activation of nonimine substrates by a chiral phosphoric acid. Mechanistic studies suggest that silylation of 11 or 12 by displacement of azide generates the active catalytic species A. Consequently, the aziridine is activated through coordination of it carbonyl with chiral silane A to produce intermediate B. Nucleophilic ring opening by azide furnishes the desymmetrized product and regenerates 11 or 12. 

The 1,5-cyclization reaction also occurs with (phosphavinyl)diazoalkanes. Thus, (methylenephosphanyl)diazoalkanes 278, generated by electrophilic diazoalkane substitution, readily cyclizes at low temperatures (321,322) (Scheme 8.68). The expected 3//-l,2,4-diazaphospholes 279 were not detected due to their rapid conversion into l//-l,2,4-diazaphospholes 280 by a silyl shift and concomitant aromatization. 

Treatment of the silyl compound, 61, above with hydrogen peroxide leads to the diol 62 which formally constitutes an oxidation as well as an electrophilic attack on the carbon atom. Classically, oxidation of nonconjugated rings to furnish their conjugated (usually aromatic) analogues is achieved by treatment with nickel(ii) peroxide however, these reactions are common and have been extensively explored for a number of different heterocyclic systems in both GHEC(1984) and CHEC-II(1996) so are not discussed further here. 

Insertion can also be carried out on the C-H bonds of heteroaromatics. Masahiro Murakami of Kyoto University has described (J. Am. Chem. Soc. 2003,125,4720) a Ru catalyst that will effect rearrangement of a silyl alkyne such as 10 into the vinylidene carbene. The intermediate Ru carbene complex is then electrophilic enough to insert into the aromatic C-H bond. The insertion is highly regioselective. The Au and the Ru alkylidene insertions are geometrically complementary, as Ru gives the E-alkcne. 

F-Teda BF4 is effective for the selective addition of fluorine to steroids in good yield, re-gioselectively and, in many cases, stereoselectively at the 6- and 16-positions, under very mild reaction conditions (Table 7).92 Further, 6 will also efficiently fluorinate silyl and alkyl enolates, enamides, carbanions, a-alkenes and actived aromatic compounds (Table 8). As an extension of this method F-Teda BF+ has been used for the electrophilic fluorination of (fluorovinyl)tin compounds affording terminal fluoroalkenes (see Table 9).88... 

The rates of bromine atom abstraction by tris(trimethylsilyl)silyl radicals from a range of /Jara-substitutcd benzyl bromides has indicated that the silyl radical is nucleophilic. In addition both the polar and spin-delocalization effects of the substituents play a role in the abstraction reaction with the latter effect greater than for H-atom abstractions.166 The perfluoroalkylation of aromatics and alkenes has been investigated using C4F9I as the source of C,. Measurement of rate constants indicated that perfluoroalkyl radicals were 2-3 orders of magnitude more reactive than the corresponding alkyl radicals. This was attributed primarily to the reaction enthalpy and far less to the electrophilic nature of the radicals.167... 

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