A review of new developments in the Friedel–Crafts alkylation – From green chemistry to asymmetric catalysis

Abstract

SummaryThe development of efficient Friedel–Crafts alkylations of arenes and heteroarenes using only catalytic amounts of a Lewis acid has gained much attention over the last decade. The new catalytic approaches described in this review are favoured over classical Friedel–Crafts conditions as benzyl-, propargyl- and allyl alcohols, or styrenes, can be used instead of toxic benzyl halides. Additionally, only low catalyst loadings are needed to provide a wide range of products. Following a short introduction about the origin and classical definition of the Friedel–Crafts reaction, the review will describe the different environmentally benign substrates which can be applied today as an approach towards greener processes. Additionally, the first diastereoselective and enantioselective Friedel–Crafts-type alkylations will be highlighted.

Direct Nucleophilic SN1‐Type Reactions of Alcohols

“…Because of the low ability of the alkynyl group to stabilize a positive charge, reactions of propargyl cations are quite limited. Quite interestingly, the coordination of the triple bond with Co 2 (CO) 6 reduces the electrophilicity of the carbocation generated by the alcohols. The well-studied and developed Nicholas reactions [15] can now be well interpreted by using the Mayr table of reactivity.…”

“…[5] Generally, carbenium ions are believed to be unstable species and highly reactive; however, there is a quantitative approach to classify the stability and reactivity of carbocations. In a recent review on Friedel-Crafts direct reactions of alcohols, [6] the concept of π-activated alcohols was introduced. A more precise and quantitative definition of activated alcohols can be derived from the stability of the carbocation generated by the alcohols.…”

Microbial biosynthesis of the anticoagulant precursor 4-hydroxycoumarin

“…In Europe, acenocoumarol and phenprocoumon are also commonly administered 5 . These drugs share the 4HC core structure but differ in 3-substitution on the pyrone ring and can be chemically synthesized using 4HC as an immediate precursor 6,7 .…”

Liquid Phase Benzylation of O-Xylene on Nano Mesoporous Lanthanum Aluminates

“…But the environmentally benign citrate-sol gel method has been rarely employed. The construction of C-C bond by FC benzylation has revolutionized organic synthesis and chemical manufacturing [12]. The product, dimethyldiphenylmethanes (DMDPM) have many useful applications [13,14].…”