Enones Friedel-Crafts alkylation

Scheme 3.24 Enantioselective conjugate Friedel-Crafts alkylations using enones as Michael acceptors.

To end this section, it has to be mentioned that there is a single example of a conjugate Friedel Crafts alkylation involving enones as Michael acceptors. In particular, a camphor-based sulfonic acid (94) has been used as catalyst in the reaction of indoles with chalcones (Scheme 4.57). It has also to be noted that the best conditions involved the use of catalyst 94 together with an ionic liquid (l-butyl-3-methyl-l//-imidazolium bromide BmimBr). However, although excellent yields were obtained for a set of different substrates tested, the enantioselectivities remained in rather low values. 

More recently, Palomo and co workers reported the application of Cu(OTf)2/(13) for highly enantioselective addition of pyrroles and indoles to a -hydroxy enones [10]. The a -hydroxy enone substrate-Cu(OTf)2/(13) catalyst system provides for excellent enantioselectivities with a variety of P substituents. It is also noteworthy that remarkable increases in enantioselectivity were observed in Friedel-Crafts alkylations of indoles when reactions were conducted under refluxing conditions (Scheme 17.5). 

Evans and coworkers [44] expanded the scope of enanti-oselective Friedel-Crafts alkylation of indoles 122 through the utilization of a series of p-snbstituted a,p-unsaturated phosphonates 123 and a,p-nnsaturated 2-acyl imidazoles 124 (Scheme 10.25). The active catalyst was proposed to be the respective complex of these enones in a bidentate fashion with bis(oxazolinyl)pyridine-scandium(III) triflate 125. Generally, this asymmetric addition reaction was found to be... 

Primary-secondary diamine catalyst 14 was found to be useful in the Friedel-Crafts alkylation reaction (Scheme 3.20). In the presence of 14/trifluoroacetic acid (TFA), alkylation of 4,7-dihydroindoles 85 with a,(3-unsaturated enones 86 proceeded well, and the desired alkylation products were obtained in high yields and with excellent enantioselectivities [56]. 

Several other asymmetric inter- as well intramolecular Friedel-Crafts alkylation with a,(3-unsaturated aldehydes have been described but without any configurative assignment [91]. Asymmetric carba-Michael additions of aldehydes to enones catalyzed by a chiral imidazolidin-4-one were reported by GeUman et al. [8] (Scheme 4.23). 

A cascade reananganent/cyclization of 2-subslituted furyl and benzofuryl enones 47 catalyzed by iridium(III) was reported by Vaidya et al. (Scheme 5.33) [33]. The process of furnishing cyclohexanones 48 with a furanylic quaternary center involves a 1,2-H shift and an intramolecular Friedel-Crafts alkylation. 

Other acids have also been explored. For instance, a heleropoly acid catalyzed Friedel-Crafts alkylation of indole and pyrrole with enones and electron-deficient olefins in water at room temperature, affording good yields at 0.3mol% catalyst loading [112]. Similarly, a carbon-based solid add was shown to catalyze effidendy the reaction of indoles with a,p-unsaturated carbonyl compounds in water, and the... 

Friedel-Crafts reactions. The reaction of osmium-complexed anisoles with electrophiles such as enones is catalyzed by TfOH. Benzylation of arenes by a reductive alkylation with arenecarbaldehyde acetals involves an intramolecular redox process (hydride shift) after protonation of the benzylic ether intermediates. 

Numerous new examples of cyclopentenone synthesis from acetylenehexacarbonyl-dicobalt complexes and norbornene derivatives have been disclosed there is evidence of steric control, and the bulky trimethylsilyl group can be employed as a removable direction-determining group to allow synthesis of 3- instead of 2-sub-stituted cyclopentenones. Reaction of (731) with sodamide in toluene gave the new octahydro-2,5-methanoazulene system (732 R = CONHj) successive hydrolysis, reduction, and esterification converted (732 R = CONHj) into (732 R = CHjOTs) which, on solvolysis, gave the homoprotoadamantane derivative (733 X = H, R R = CH2) in high yield.The carboxylic acid (732 R = COjH) underwent spontaneous Friedel-Crafts intramolecular acylation on conversion into its acid chloride to give (733 XX = O R R = CHj) and (733 XX = O, R = Cl, R = Me). Reaction of methyl a-bromocrotonate (mixture of E- and Z-isomers) with the enolates of cyclohex-2-enone affords a mixture of stereoisomeric tricyclo-[3,2,l,0 ]octan-6-ones (734 R —R are variously H or alkyl) in moderate yield. The reaction involves double Michael addition and subsequent substitution. 

Under Friedel-Crafts conditions, PhCOCI reacts with various silicon compounds. Thus p-diketones are easily obtained from enoxysUanes (eq 21). Conversely, vinyl-, aryl-, and allyl-silanes lead to the corresponding vinyl, aryl, and allyl ketones in good yields" (eq 22" and eq 23" ). Vinylsilanes can lead to a mixture of p-chloro alkyl ketones and conjugated enones a basic treatment is then necessary to obtain only the enone (eq 23). 

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