Friedel-Crafts-type reactions, asymmetric

In conjunction with their Friedel-Crafts alkylation, Terada et al. found phosphoric acid (R)-3m (2 mol%, R = 9-anthryl) bearing a bulky 9-anthryl group to mediate the asymmetric Friedel-Crafts-type reaction of a-diazoester 22a with iV-acylated aldimines 26 (Scheme 10). a-Diazo-P-amino esters 27 were obtained in moderate yields (62-89%) and very good enantioselectivities (91-97% ee) [20],... 

Enantioselective vanadium and niobium catalysts provide chemists with new and powerful tools for the efficient preparation of optically active molecules. Over the past few decades, the use of vanadium and niobium catalysts has been extended to a variety of different and complementaiy asymmetric reactions. These reactions include cyanide additions, oxidative coupling of 2-naphthols, Friedel-Crafts-type reactions, pinacol couplings, Diels-Alder reactions, Mannich-type reactions, desymmetrisation of epoxides and aziridines, hydroaminations, hydroaminoalkylations, sulfoxida-tions, epoxidations, and oxidation of a-hydroxy carbo) lates Thus, their major applications are in Lewis acid-based chemistiy and redox chemistry. In particular, vanadium is attractive as a metal catalyst in organic synthesis because of its natural abundance as well as its relatively low toxicity and moisture sensitivity compared with other metals. The fact that vanadium is present in nature in equal abundance to zinc (albeit in a more widely distributed form and more difficult to access) is not widely appreciated. Inspired by the activation of substrates in nature [e.g. bromoperoxidase. 

Figure 14.4 Perfluorinated CPN and CPD derivatives developed for asymmetric Friedel-Crafts-type reactions in Solkane 365 mfc.

In 2006, Zhou s group reported a copper-catalyzed asymmetric synthesis (it was described in the paper as Friedel-Crafts-type reaction) using Al-sulfonyl aldimines with indoles to provide a simple approach to optically active 3-indolylmethanamine derivatives with high enantioselectivity. A bis-oxazoline-copper complex was used (Scheme 6.37) [50]. 

Table 20 Asymmetric Friedel-Crafts-type reactions of indole with chalcone derivatives using a chiral Hg-S.S -SiPhs-BINOL-barium catalyst...

In this work, the combination of cinchona-alkaloid-derived primary amine and Au(I) phosphine complex has been employed to effect two consecutive Friedel-Crafts-type reactions of pyrrole in one pot to furnish 2,3-annulated pyrroles containing a seven-membered ring (eq 1) This reaction proceeds through initial asymmetric 1,4-addition of p)rrole to enones catalyzed by the primary amine followed by an intramolecular 7-c/ido-dig cycliza-tion catalyzed by the Au(I) phosphine complex. 

The Pictet-Spengler reaction is the method of choice for the preparation of tetrahydro-P-carbolines, which represent structural elements of several natural products such as biologically active alkaloids. It proceeds via a condensation of a carbonyl compound with a tryptamine followed by a Friedel-Crafts-type cyclization. In 2004, Jacobsen et al. reported the first catalytic asymmetric variant [25]. This acyl-Pictet-Spengler reaction involves an N-acyliminium ion as intermediate and is promoted by a chiral thiourea (general Brpnsted acid catalysis). 

Scheme 14.7 Catalytic asymmetric conjugate Friedel-Crafts-type addition of indoles to enones catalysed by primaiy amine Cinchona catalysts, and reaction transition state.

Different from the hydroxyalkylation reactions using carbonyl compounds as substrates, Nicolaou s and Macmillan s groups developed independently the intramolecular asymmetric Friedel-Crafts-type a-arylation of aldehydes with electron-enriched arenes based on the SOMO activation strategy. Using chiral imidazolidione as catalyst, a series of cyclic aldehydes were obtained in good yields and enantioselectivities with cerium ammonium nitrate (CAN) as single electron transfer oxidant [46]. 

D. Enders, C. Wang, M. Mukanova, A. Greb, Chem. Commun. 2010, 46, 2447-2449. Organocatalytic asymmetric synthesis of polyfunctionalized 3-(cyclohexenyhnethyl)-indoles via a quadruple domino Friedel-Crafts-type/Michael/Michaehaldol condensation reaction. 

In 2009, Nicolaou et al. reported the asymmetric total synthesis of the antitumour natural product demethyl calamenene based on an enantioselective organocatalytic intramolecular Friedel-Crafts type a-arylation of aldehydes bearing electron-donating groups on their aromatic nucleus. This reaction, catalysed by chiral /err-butyl-3-methyl-5-benzyl-4-imidazolidinone, afforded the corresponding polycyclic products in good to high yields and with excellent enantioselectivities for a broad variety of aldehydes, as shown in Scheme 10.4. 

Later, You et al. investigated relay catalysis consisting of a combination of the same ruthenium catalyst and a closely related chiral BINOL-derived phosphoric acid. As shown in Scheme 7.42, the use of this catalyst system in an asymmetric domino intramolecular Friedel-Crafts-type-aza-Michael reaction allowed a range of chiral fused indoles to be achieved in high yields and moderate to high enantioselectivities from the corresponding enones and indolyl olefins. 

Kobayashi et al. also reported asymmetric Friedel-Crafts-type alkylation reactions of an indole with a chalcone (Scheme 5) [49]. A chiral calcium complex... 

The amino-acid-derived imidazolidinones, so-called MacMillan catalysts, efficiently form iminium ions with a, 3-unsaturated aldehydes and catalyze a Friedel-Crafts-type Michael reaction. Based on this strategy, Hanes-sian and co-workers reported on a practical asymmetric synthesis of indole derivative (S)-(—)-14, which is a precursor of drug prototype (S)-(+)-15, a candidate for treatment of migraine headaches (Scheme 27.2). In this synthesis, nitrogen-containing aldehyde 11 was able to react with 5-bromoindole 10 in the presence of (/ ,/ )-MacMillan catalyst 12 to give the adduct 13 in quantitative yield with 92% ee. 

Additions to quinoline derivatives also continued to be reported last year. Chiral dihydroquinoline-2-nitriles 55 were prepared in up to 91% ee via a catalytic, asymmetric Reissert-type reaction promoted by a Lewis acid-Lewis base bifunctional catalyst. The dihydroquinoline-2-nitrile derivatives can be converted to tetrahydroquinoline-2-carboxylates without any loss of enantiomeric purity <00JA6327>. In addition the cyanomethyl group was introduced selectively at the C2-position of quinoline derivatives by reaction of trimethylsilylacetonitrile with quinolinium methiodides in the presence of CsF <00JOC907>. The reaction of quinolylmethyl and l-(quinolyl)ethylacetates with dimethylmalonate anion in the presence of Pd(0) was reported. Products of nucleophilic substitution and elimination and reduction products were obtained . Pyridoquinolines were prepared in one step from quinolines and 6-substituted quinolines under Friedel-Crafts conditions <00JCS(P1)2898>. 

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. 

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. 

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... 

The area of reactions of phosphate derivatives has been dominated by highly stereoselective reactions in which the latter were used as chiral catalysts or achiral reagents. Among this group of reactions, it is worthy to note several asymmetric reactions ring opening of w 50-aziridinium and episulfonium ions, addition of alcohols to imines, 1,3-dipolar addition of aldehydes, amino esters and dipolarophiles, protonation of silyl enol ethers, epoxidation of a,p-unsaturated aldehydes, aza-ene-type reactions as well as asymmetric versions of named reactions Mannich, Friedel-Crafts, Kabachnik-Fields, aza-Darzens and aza-Henry. 

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