Friedel-Crafts reactions cyclopropanes

The Lewis acid-catalysed rearrangement of arylvinylidenecyclopropanes having three substituents at the 1- and 2-positions of the cyclopropane to give 6a//-benzole] fluorine or phenyl-l//-indene derivatives via an intramolecular Friedel-Crafts reaction under mild reaction conditions has been reported (Scheme 57).92... 

Aromatic hydrocarbons, such as benzene add to alkenes using a ruthenium catalyst a catalytic mixture of AuCVAgSbFs, or a rhodium catalyst, and ruthenium complexes catalyze the addition of heteroaromatic compounds, such as pyridine, to alkynes. Such alkylation reactions are clearly reminiscent of the Friedel-Crafts reaction (11-11). Palladium catalysts can also be used to for the addition of aromatic compounds to alkynes, and rhodium catalysts for addition to alkenes (with microwave irradiation). " Note that vinyhdene cyclopropanes react with furans and a palladium catalyst to give aUylically substituted furans. ... 

A four-step synthesis may be considered by linking together the Friedel-Crafts reaction with the synthesis of a chalcone (Experiment 61) and then preparing an epoxide (Experiment 62) from the chalcone and/or a cyclopropanated chalcone (Experiment 63). It is likely that the Friedel-Crafts reaction should produce enough acylated product for the reactions that follow. If you choose to link together the chalcone synthesis followed by epoxidation and cyclopropanation, it is suggested that you choose to prepare the acetyl derivatives of toluene, p-xylene, mesitylene, or anisole and use one of the recommended aldehydes shown in the following table to make the chalcone in Experiment 61. 

The concept was soon expanded to other reactions, keeping salmon sperm DNA, Cu, and intercalating ligands (mostly dmbipy). Using these systems, asymmetric fluorinations, Michael and oxa-Michael additions, Friedel—Crafts reactions were reported, as well as a syn-hydration (in water), and an intramolecular cyclopropanation [6c, 8]. 

The elfectiveness of imidazolidinone of type 11 was confirmed by successful application to a broad range of chemical transformations, including cycloadditions, conjugate additions, Friedel-Crafts alkylations, Mukaiyama-Michael additions, hydrogenations, cyclopropanations, and epoxidations. A summary of these enantio-selective iminium catalyzed processes is provided by reaction subclass. 

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... 

Simple 3-acylfurans are not accessible by direct Friedel-Crafts-type substitution of furan, but a most unusual route to these compounds has been discovered. Thus, reaction of the stannylated cyclopropane derivative 1 with acid chlorides (RCOC1) in refluxing toluene for 5 hours gave the dihydrofurans 2 in 64-83% yield. Treatment of 2 with 1.2 equivalents of BF3,OEt2 in dichloromethane at -78°C followed by slow wanning of the reaction mixture to room temperature gave the 3-acylfurans 3 in 30-62% yield. 

Acylation of alkenes. Friedel-Crafts acylation (AlCl,) of alkenes suffers from lack of selectivity and low yields. The reaction is markedly improved by use of CHdj-Zn/Cu (3, 255) as catalyst. No cyclopropanation is observed. 

Surprisingly, little follow-up work on this idea of small molecule asymmetric catalysis appeared for the next 25 years. In the late 1980s, Agami reported the asymmetric intramolecular aldol reaction of acyclic diketones with (S)-proline as the catalyst. It was not nntil the twenty-first centnry, however, when this notion of organocatalysts became fnlly exploited. List and Barbas ° pioneered enam-ines as catalysts for aldol and Mannich and related reactions. MacMillan has developed a variety of imininm-based catalysts prodncing large asymmetric indnction for Diels-Alder chemistry, Friedel-Crafts alkylations, Mnkaiyama-Michael and cyclopropanation " reactions. 

Anhydrides of cis-cyclopropane-1,2-dicarboxy lie acids are converted to CM-2-acylcyclo-propanecarboxylic acids using various reagents. The outcome of the reaction is sensitive to the reaction conditions. Treatment of c i-3-oxabicyclo[3.1.0]hexane-2,4-dione with phenylmag-nesium bromide at low temperature" and dimethylcadmium at room temperature gave c/s-2-benzoyl- and c -2-acetylcyclopropanecarboxylic acid in 53 and 70% yield, respectively in addition minor amounts of disubstituted lactones were formed. 1129,1251 jjowever, no lactone was formed when cis-2-benzoylcyclopropanecarboxylic acid was prepared in 66% yield by reacting c -3-oxabicyclo[3.1.0]hexane-2,4-dione with benzene under Friedel-Crafts conditions." ... 

Cyclopropyl ketones can be synthesized directly from silyl enol ethers by addition of acid chlorides to a reaction mixture of Simmons-Smith reagent and the enol ether (Scheme 3). In this reaction, the Znl by-product of the cyclopropanation sequence acts as a Friedel-Crafts type catalyst to activate the acid chloride. In related studies, Grignon-Dubois and co-workers have shown that the Friedel-Crafts acylation of cyclopropyltrimethylsilanes also provides an expeditious route to cyclopropyl ketones. 

Friedel-Crafts chemistry at an asymmetric center generally proceeds with racemization, but the use of mesylates or chlorosul-fonates as leaving groups has resulted in alkylations with excellent control of stereochemistry. The reactions proceed with inversion of configuration (eq 3). Cyclopropane derivatives have been used as three-carbon units in acylation reactions (eq 4). In conjunction with triethy Isilane, a net alkylation is possible under acylation conditions (eq 5). These conditions are compatible with halogen atoms present elsewhere in the molecule. Acylation reactions of phenolic compounds with heteroaromatic systems have also been accomplished (eq 6). ... 

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