Michael-type Friedel-Crafts reaction

Chen and co-workers presented, in 2007, a Michael-type Friedel-Crafts reaction of 2-naphthols and trans-P-nitroalkenes utilizing the bifunctional activating mode of cinchonine-derived catalyst 117 [277]. The nitroalkene was activated and steri-cally orientated by double hydrogen bonding, while the tertiary amino group interacts with the naphthol hydroxy group to activate the naphthol for the nucleophilic P-attack at the Michael acceptor nitroalkene (Scheme 6.117). 

D-Camphorsulfonic acid (d-CSA) was identified as catalyst for the enantioselec-tive Michael-type Friedel-Crafts reactions of indoles with aromatic enones ArCH= CHCOAr to afford the corresponding /i-indolyl ketones in excellent yields and moderate enantioselectivities. A surprising synergistic effect was discovered between [Bmim] Br and d-CSA, which may originate from the catalytic Lewis acid activation of the Brpnsted acid.162... 

Among various a-methylene-8-lactones, derivatives with the S-lactone ring fused with the aryl ring having a structure of 3,4-dihydrocoumarins occupy prominent position and received substantial attention in the past few years. In 2007, Krawczyk and coworkers [76] demonstrated that the 3,4-dihydrocoumarin framework can be accessed by a means of Michael-type Friedel-Crafts reaction between 3-aryl-2-diethoxyphosphorylacrylic acids 181 and electron-rich hydroxyarenes 182... 

In 2006, Xu and Xia et al. revealed the catalytic activity of commercially available D-camphorsulfonic acid (CS A) in the enantioselective Michael-type Friedel-Crafts addition of indoles 29 to chalcones 180 attaining moderate enantiomeric excess (75-96%, 0-37% ee) for the corresponding p-indolyl ketones 181 (Scheme 76) [95], This constitutes the first report on the stereoselectivity of o-CSA-mediated transformations. In the course of their studies, the authors discovered a synergistic effect between the ionic liquid BmimBr (l-butyl-3-methyl-l/f-imidazohum bromide) and d-CSA. For a range of indoles 29 and chalcone derivatives 180, the preformed BmimBr-CSA complex (24 mol%) gave improved asymmetric induction compared to d-CSA (5 mol%) alone, along with similar or slightly better yields of P-indolyl ketones 181 (74-96%, 13-58% ee). The authors attribute the beneficial effect of the BmimBr-D-CSA combination to the catalytic Lewis acid activation of Brpnsted acids (LBA). Notably, the direct addition of BmimBr to the reaction mixture of indole, chalcone, d-CSA in acetonitrile did not influence the catalytic efficiency. 

SCHEME 5.8 Michael-type Friedel-Crafts alkylation reaction mediated by chiial TlPS-pybox-[Sc(III)]... 

Wang elegantly demonstrated the potentiality of chiral diarylprolinol ether 54 in the synthesis of chromanes 56 via enantioselective Michael-type Friedel-Crafts alkylation/cychzation cascade synthetic sequence between 5a and a,p-unsaturated aldehydes 37a [30a]. Under optimal conditions, moderate diastereoselectivity and high enantioselectivity were obtained. Differently, phenol was found unreactive (Scheme 5.17a). The same team years later documented also the activity of a rosin-derived tertiary amine-thiourea 55 in similar process involving 1- and 2-naphthols and P,y-unsaturated a-ketoesters 25 (Scheme 5.17b) [30b]. A proposed model of the enantiodiscrimi-nating step of the reaction is also provided by the authors (58). 

We will show here the classification procedure with a specific dataset [28]. A reaction center, the addition of a C-H bond to a C=C double bond, was chosen that comprised a variety of different reaction types such as Michael additions, Friedel-Crafts alkylation of aromatic compounds by alkenes, or photochemical reactions. We wanted to see whether these different reaction types can be discerned by this... 

There is some similarity between the cracking of petroleum and the cracking of biomass. However, biomass is more complex chemically both in terms of structrual types and functional groups. In petrochemistry, hydrocarbons are fractionated and they are then functionalized by oxidation, halogenation, nitration and other chemical processes so as to add value. The commodity chemicals are then built up into more complex molecules using such popular synthetic methods as Friedel Craft reactions, Michael and aldol condensations, and Heck and Suzuki couplings. The speciality products of these reactions are then further elaborated into formulations for use in everyday applications ranging from personal care... 

Enantioselective Michael-type indole Friedel-Crafts reaction with a,P-unsaturated acyl thiazole has been disclosed <07JA10029>. Reaction of indole 127 and 128 in the presence of 10% mol of bis(oxazolinyl)pyridine-scandium(III) triflate complex 129 in acetonitrile at -40 °C affords 130 with high level of enantioselectivity. 

To date, no known bisindole alkaloid has been shown to be only an artefact. In addition, no experimental evidence exists which undermines the assumption that bisindole alkaloids are actually formed from the completed monomeric partners. Support for this idea is derived from the kind of reactions apparently necessary to effect such dimerisations which are known biogenetic processes amine-aldehyde condensations, Mannich reactions, Michael additions, Friedel-Craft type condensations, Diels-Alder type processes, radical coupling etc. The observation that the skeletal distribution amongst monomeric alkaloids is reflected throughout the dimeric series lends further support. 

Enders et al. [75] developed a synthesis of polyfunctionalized 3-(cyclohex-enylmethyl)-indoles 125 via a quadruple domino Friedel-Crafts-type Michael-Michael-aldol condensation reaction, in 2010. This cascade sequence is initiated by a Friedel-Crafts reaction of indole (126) by an iminium activation mode to the enal, followed sequentially by an enamine- and an iminium-mediated Michael addition. After an intramolecular aldol-condensation, four C-C bonds are formed and the domino product is constructed bearing three contiguous stereogenic centers (Scheme 10.34). 

A chiral Sc-pybox catalyst from Sc(OTf)3 catalyzes a highly enantioselective Michael-type indole Friedel-Crafts reactions with a variety of )3-substitnfed a, -unsaturated acyl phosphonates and -substituted a,j8-unsaturated 2-acyl imidazoles (Scheme 2). The acyl phosphonate products were efficiently ttansformed into the corresponding esters and amides, whereas the acyl imidazole prodncts were converted to more diverse functionalities snch as esters, amides, carboxyhc acids, ketones, and aldehydes. A nuld and efficient cleavage protocol for the diversification of the 2-acyl imidazole prodncts ntihzing methylating conditions was also developed. 

Recently, the Michael-type asymmetric Friedel-Crafts reaction of electron-deficient alkenes has been established as an important route to chiral benzylic stereocentres. " However, applications of this methodology for the synthesis of all-carbon quaternary stereocentres are conspicuously limited. PFMonosubstituted nitroalkenes have turned out to be active substrates in... 

A fourfold anionic sequence which is not initiated by a Michael but an aldol reaction has been reported by the group of Suginome and Ito (Scheme 2.129) [295]. In this approach, the borylallylsilane 2-573 reacts selectively in the presence of TiCl4 with two different aldehydes which are added sequentially to the reaction mixture. First, a Lewis acid-mediated allylation of the aldehyde with 2-573 takes place to form a homoallylic alcohol which reacts with the second aldehyde under formation of the oxenium ion 2-574. The sequence is terminated by a Prins-type cyclization of 2-574 and an intramolecular Friedel-Crafts alkylation of the intermediate 2-575 with formation of the fraws-1,2-be rizoxadeca lines 2-576 as single diastereomers. 

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. 

The analogy between imines and carbonyls was introduced earlier, and just as 1,3-dike-tonate complexes undergo electrophilic substitution reactions at the 2-position, so do their nitrogen analogues. Reactions of this type are commonly observed in macrocyclic ligands, and many examples are known. Electrophilic reactions ranging from nitration and Friedel-Crafts acylation to Michael addition have been described. Reactions of 1,3-diimi-nes and of 3-iminoketones are well known. The reactions are useful for the synthesis of derivatised macrocyclic complexes, as in the preparation of the nickel(n) complex of a nitro-substituted ligand depicted in Fig. 5-12. 

Bicyclic 3a//-cyclopentene[8 annulcnc-l,4-(5//,9a//)-dioncs undergo three types of acid-induced transannular reactions (1) Michael addition (5-exo-trig or 6-exo-trig) leading to the tetracyclic diones, (2) 3 + 2-cycloaddition followed by a novel sequential skeletal rearrangement to 2-naphthalenone derivatives, (3) ipso-Friedel-Crafts alkylation accompanied by the rearomatization and the loss of water (Scheme 25). The factors that control the reaction mode of these transannular cyclizations are discussed... 

Scheme 1. Gold-catalyzed C—C-coupling reaction Friedel-Crafts-type or Michael-type reaction ...

Alder, cyanation, allylation, Michael reaction, and Friedel-Crafts acylation). The same catalyst was also effective in three-component reactions such as Mannich-type reactions, Strecker, and quinoline-forming reactions. The polymer catalyst was recovered and reused many times without loss of activity (Eq. 31). 

Catalytic enantioselective Friedel-Crafts type addition reactions of electron-rich arenes (indoles, pyrroles etc.) with Michael acceptors have been well developed in the past years. These reactions generally are enabled by chiral Lewis acids or organocatalysts (Scheme 6.24). Chiral Lewis acid-catalyzed processes usually require bidentate substrates (chelating a,p-unsatu-rated compounds) for strong chelation activation. Monodentate compounds (simple a,p-unsaturated compounds) prove to be less selective. With chiral... 

The Friedel-Crafts alkylation is one of the oldest synthetic methodologies known. The catalytic asymmetric version of the reaction [311] enables the preparation of important chiral building blocks. Electron-rich aromatic and heteroaromatic compounds have been productively used in organocatalyzed enantioselective inter- and intramolecular Friedel-Craft-[312] type conjugate additions over different Michael acceptors such as, a,p-unsaturated aldehydes, a,P-unsaturated ketones, nitroole-fins, and a,p-unsaturated acyl phosphonates. 

The combination of an imine derived from the reaction of acrolein organocatalyst 1 with simple indoles 84 and nitroalkenes 85 affords the 3-(cyclohexenylmethyl)-indoles 86 (Scheme 7.16) [59]. In this reaction, the indole 84 initiates the Friedel-Crafts-type reaction followed by a Michael reaction with nitroalkenes 85 to the intermediate 87. From this process, a hydrolysis takes place and the resulting compound enters another catalytic cycle involving a Michael/aldol condensation reaction similar to those reported previously. 

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