Friedel Crafts and Related Reactions

Friedel-Crafts reactions of aromatic compounds with acyl chlorides, anhydrides, or related compounds in the presence of a Lewis acid have been reviewed [429,430], Among a variety of Lewis acids, the most typical is AICI3, although there are reactions as shown in Eqs (172) [431], (173) [432], and (174) [433] in which TiCU was used as the Lewis acid. 

It is well known that Friedel-Crafts acylation of aromatic compounds requires more than one equivalent of a Lewis acid relative to the substrate to bring the reaction to the completion, because the ketone produced deactivates the Lewis acid by complexation. Despite this, only 1 mol % TiCl(OTf)3 and 10 mol % TfOH in di-chloromethane or acetonitrile proved sufficient for the acylation shown in Eq. (175) this is, therefore, a catalytic Friedel-Crafts reaction [434]. The high regioselectivity obtained is also useful. 

The formylation of metalated sp carbons, for example in a stannylbenzene (Eq. 185) [458] or in vinylsilanes [459,460] (Eq. 186), with Cl2CH(OMe) and TiCU, in which the ipso carbon to the stannyl or silyl group is selectively formylated, has been reported. The formylation of a vinylsilane was used in the preparation of a terpene aldehyde, nuciferal, as shown in Eq. (186) [461]. 

The double bond of methylenecyclopropanes is alkylated by carbonyl compounds in the presence of TiCLt [483]. While the bicyclic methylenecyclopropane in Eq. (199) suffered simple alkylation followed by chlorination to give the product as a single stereoisomer, monocyclic methylenecyclopropanes showed a quite different behavior, including a ring opening reaction to give alcohols with an allyl chloride moiety (Eq. 200). 

Intramolecular alkylation of olefins has been investigated extensively, perhaps because it might be synthetically more useful than the intermolecular version, because the regiochemical issue of both reacting electrophile and accepting olefin should less frequently arise. Intramolecular acylation of carbon-carbon double bonds, which is still a convenient method for the preparation of carbocyclic skeletons, has been con- 

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. 

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Friedel-Crafts and Related Reactions, Vols. I-IV (ed), 1963-1964. Carbonium Ions (ed. with Schleyer), Vols. I-V, 1968-1972. Friedel-Crafts Chemistry, 1973. 

G. A. Olah, ed., Friedel-Crafts and Related Reactions, Wiley-Interscience, New York, 1964. 

For a monograph, see Roberts, R.M. Khalaf, A.A. Friedel-Crafts Alkylation Chemistry Marcel Dekker NY, 1984. For a treatise on Friedel-Crafts reactions in general, see Olah, G.A. Friedel-Crafts and Related Reactions Wiley NY, 1963-1965. Volume 1 covers general aspects, such as catalyst activity, intermediate complexes, and so on. Volume 2 covers alkylation and related reactions. In this volume the various reagents are treated by the indicated authors as follows alkenes and alkanes, Patinkin, S.H. Friedman, B.S. p. 1 ... 

Author. Friedel-Crafts and Related Reaction, Interscience Publishers, New York, 1963, 1, pp 205. 

G. A. Olah, ed., Friedel-Crafts and Related Reactions, Vols. 1-1V, Wiley-Interscience, New York, 1962-1964. R. M. Roberts and A. A. Khalaf, Friedel-Crafts Alkylation Chemistry, Marcel Dekker, New York, 1984. 

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