Friedel nucleophilic addition

The observed preferential electrophilic attack on carbon D of C70 under Friedel-Crafts conditions (CHC13/A1C13) is consistent with the large HOMO coefficient of this carbon (Figure 13). This is in contrast to the fact that nucleophilic addition (7,35-38) and cycloaddition (38-40) to C70 favor carbons A and B, which are most pyramidalized and have large LUMO coefficients (Figure 13). 

In 1977, an article from the authors laboratories [9] reported an TiCV mediated coupling reaction of 1-alkoxy-l-siloxy-cyclopropane with aldehydes (Scheme 1), in which the intermediate formation of a titanium homoenolate (path b) was postulated instead of a then-more-likely Friedel-Crafts-like mechanism (path a). This finding some years later led to the isolation of the first stable metal homoenolate [10] that exhibits considerable nucleophilic reactivity toward (external) electrophiles. Although the metal-carbon bond in this titanium complex is essentially covalent, such titanium species underwent ready nucleophilic addition onto carbonyl compounds to give 4-hydroxy esters in good yield. Since then a number of characterizable metal homoenolates have been prepared from siloxycyclopropanes [11], The repertoire of metal homoenolate reactions now covers most of the standard reaction types ranging from simple... 

Imlnium ions. N-Arylsulfonyliminium ions are generated from N-arylsulfonyl-a-amino acid chlorides on treatment with AgSOjCFj. These iminium ions are very reactive and readily undergo nucleophilic addition or intramolecular Friedel-Crafts reactions. ... 

Carbon disulfide is an important industrial solvent for the extraction of oils and waxes. In organic chemistry, it is widely used as a solvent for Friedel-Crafts reactions. Carbon disulfide functions as an electrophilic reagent. It is more susceptible than carbon dioxide to nucleophilic attack as the energy required to convert C=S to C-S (188 kJmol 1) is much less than required for the analogous conversion of C=0 to C-0 (305 kJmol 1). Carbon disulfide (1) thus undergoes nucleophilic additions with alcohols and phenols to yield the corresponding xanthates (2) (the xanthate reaction) (Scheme 2)... 

Functionalization of Ceo through C-C bond formation has been achieved by a variety of methods nucleophilic addition of carbanions, quenching of Ceo anions with alkyl halides, Friedel-Crafts arylation, radical addition, and cycloadditions. 

In the chemistry of epoxides with aromatic compounds, a unique AICI3-promoted reaction has been reported by Tsuboi and coworkers [87]. In the presence of AICI3 (3 equivalent), the reaction of 2-chloro-2,3-epoxycarboxylic ester (89a) with toluene did not give any normal Friedel-Crafts products, but the product (90a) derived from nucleophilic addition of toluene to (89a) was obtained in 81% yield with syn selectivity (Scheme 6.68). AICI3 also promoted intramolecular version of this nucleophilic addition reaction. 

The first organocatalytic asymmetric carbon nucleophilic addition to enals was reported by MacMillan in 2001 [15]. MacMillan reported the first Friedel-Craft alkylation between N-substituted pyrroles and enals promoted by catalyst 7. The reaction renders the final compounds in good yields and enantioselectivities (Scheme 33.4). 

Iminium catalysis is another key catalytic concept in aminocatalysis. Initialworkwas disclosed by MacMillan for the Diels-Alder reaction of cyclopentadiene and a,P-unsaturated aldehydes [12], but it was rapidly extended to Michael additions (including Friedel-Crafts reactions). Now iminium catalysis has been established as a general mode for nucleophilic addition to a,]3-unsaturated carbonyl compounds. 

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