Electrophilic aromatic substitution reactions chiral electrophile

Regioselectivity in the formation of regioisomers is also observed in electrophilic aromatic substitution reactions. In the case of monosubstituted benzene derivatives, there are three possible regiosomeric products that form at different rates, based on the mechanism of the reaction (see Figure 13). see also Berzelius, Jons Jakob Chirality Dalton, John Davy, Humphry Molecular Structure Scheele, Carl Wohler, Friedrich. 

Despite the prevalence and importance of atropisomerism in organic structures, the field of asymmetric catalysis has not yet recorded extensive success in the development of catalysts, which control this stereochemical feature. Indeed, catalytic reactions of this nature are presently rare and only modest atropi-somer selectivity has been observed. In this context. Miller s group recently developed the DKR of biaryl atropisomers via peptide-catalysed asymmetric bromination. The reaction proceeded via an atropisomer-selective electrophilic aromatic substitution reaction using a simple bromination reagent such as A7-bromophthtalimide. As shown in Scheme 5.27, a series of chiral bromi-nated biaryl compounds could be prepared with excellent enantioselectivities of... 

Ferrocene behaves like an aromatic compound activated for electrophilic substitution reactions. Thus, only minor modifications of experimental procedures developed for aromatics are necessary to obtain ferrocene derivatives (a useful review on general methods is given by Schldgl and Falk [42]). For central chiral ferrocenes, resolution of the racemate is a frequently applied technique. Traditionally, resolutions are best achieved by salt formation between a chiral acid or base and the... 

Other chiral glycine cation equivalents useful for the synthesis of enantiomerically pure a-amino acids are (174) and (175). However, acid-catalyzed reactions of these A/-acyliminium precursors with alkenes or alkynes have not been reported yet. The BF3 Et20-mediated electrophilic aromatic substitution of (175) onto anisole in 98% diastereoselectivity deserves mention here. ... 

A variety of optically active 4,4-disubstituted allenecarboxylates 245 were provided by HWE reaction of intermediate disubstituted ketene acetates 244 with homochiral HWE reagents 246 developed by Tanaka and co-workers (Scheme 4.63) [99]. a,a-Di-substituted phenyl or 2,6-di-tert-butyl-4-methylphenyl (BHT) acetates 243 were used for the formation of 245 [100]. Addition of ZnCl2 to a solution of the lithiated phos-phonate may cause binding of the rigidly chelated phosphonate anion by Zn2+, where the axially chiral binaphthyl group dictates the orientation of the approach to the electrophile from the less hindered si phase of the reagent. Similarly, the aryl phosphorus methylphosphonium salt 248 was converted to a titanium ylide, which was condensed with aromatic aldehydes to provide allenes 249 with poor ee (Scheme 4.64) [101]. 

Another useful variation is the Pictet-Spengler isoquinoline synthesis, also known as the Pictet-Spengler reaction. The reactive intermediate is an iminium ion 49 rather than an oxygen-stabilized cation, but attack at the electrophilic carbon of the C=N unit (see 16-31) leads to an isoquinoline derivative. When a p-aryla-mine reacts with an aldehyde, the product is an iminium salt, which cyclizes with an aromatic ring to complete the reaction and generate a tetrahydroisoquinoline." ° A variety of aldehydes can be used, and substitution on the aromatic ring leads to many derivatives. When the reaction is done in the presence of a chiral thiourea catalyst, good enantioselectivity was observed." ... 

The Friedel Crafts (F C) reaction via activation of electrophiles functionalized by a nitrogen atom, such as imines, is undoubtedly the most practical and atom eco nomical approach to introduce a nitrogen substituted side chain to aromatic com pounds. The enantioselective version of the F C reaction of nitrogen substituted substrates, including imines, with electron rich aromatic compounds enables effi cient access to enantioenriched aryl methanamine derivatives [37[. Several excellent approaches to highly enantioselective F C reactions have been established using chiral phosphoric acid catalysts. 

V-Arene complexes have been developed as reagents for organic synthesis. A vast majority of this work has been reported by Harmann. - V Arene and heteroarene complexes have been generated on (NHjjjOs " and more recently on TpM(CO)(L) in which M = Re, Mo, and W, and L = CO or NO. The latter chiral-at-metal system has been resolved. This t coordination leads to de-aromatization of the arene, in effect isolating the diene unit for reactions, as depicted in Figure 11.6. The chemistry of T -arene complexes is therefore more akin to the chemistry of dienes, and the chemistry of T -furans is more akin of that of vinyl ethers than it is to the chemistry of electron-poor T -arenes. Harmann has developed Diels-Alder reactions of the diene unit and additions of electrophiles to the vinyl ether unit. - In one case, coordination of furan also led to the ability to conduct nucleophilic substitution on the coordinated olefin. ... 

In this segment, You and coworkers documented the snitabUity of the in situ genwated electrophilic indolinium in the chiral Br0nsted acid-mediated enantioselective decoration of electron-rich aromatic hydrocarbons [34]. Both alcohols and NTs amide compounds proved suitability for the enantioselective alkylation of alkoxy-substituted benzenes in inter- and intramolecular fashion. Contact ion pairing between the chiral BA anion and the indolinium intermediate was accounted as active species during the enantiodiscriminating event of the alkylation reaction (Scheme 5.20). 

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