Friedel catalytic asymmetric

Fig. 34 Catalytic asymmetric Friedel-Crafts alkylation of indoles catalyzed by 60...

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>. 

The Friedel-Crafts reaction is one of the most important and versatile tools for the formation of carbon-carbon bonds in the synthesis of substituted aromatic and heteroaromatic compounds present in numerous natural products and drugs. Catalytic asymmetric variants using either metal complexes or organic molecules attracted considerable attention over the last few years. 

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). 

The synthesis of the optically active chroman 489 can be achieved by use of a catalytic asymmetric tandem oxa-Michael addition Friedel-Crafts alkylation sequence between 3-methoxyphenol and (/. (-methyl 2-oxo-4-phenylbut-3-enoate. The chiral C2-symmetric box managanese(n)- complex 490 exerts excellent stereocontrol upon the reaction (Equation 200) <20030BC1953>, whereas only moderate enantioselectivity is observed in the presence of a chiral C2-symmetric 2,2 -bipyridyl copper(n)- complex (42% = ee) <20050L901>. 

Kadyrov R, Riermeier TH (2003) Highly enantioselective hydrogen-transfer reductive amination catalytic asymmetric synthesis of primary amines. Angew Chem Int Ed Engl 42 5472-5474 Kang Q, Zhao ZA, You SL (2007) Highly enantioselective Friedel-Crafts reaction of indoles with imines by a chiral phosphoric acid. J Am Chem Soc 129 1484-1485... 

The 3-indolyl methanamine structural motif 503 is embedded in numerous indole alkaloids and synthetic indole derivatives . An efficient catalytic asymmetric Friedel-Crafts reaction of indoles 501 with imines 502 provides a direct, convergent, and versatile method for the highly enantioselective construction of 3-indolyl methanamines 503 from readily accessible achiral precursors (Scheme 101) <2006JA8156 and references therein>. 

Friedel-Crafts alkylation is one of the most frequently used and widely studied reactions in organic chemistry. Since the initial discovery by Charles Friedel and James Mason Crafts in 1877, a large number of applications have emerged for the construction of substituted aromatic compounds. Friedel-Crafts alkylation processes involve the replacement of C—H bond of an aromatic ring by an electrophilic partner in the presence of a Lewis acid or Bronsted acid catalyst. Particularly, catalytic asymmetric Friedel-Crafts alkylation is a very attractive, direct, and atom-economic approach for the synthesis of optically active aromatic compounds. However, it took more than 100 years from the discovery of this reaction until the first catalytic asymmetric Friedel-Crafts (AFC) alkylation of naphthol and ethyl pyruvate was realized by Erker in 1990. Nowadays, owing to continued efforts in developing... 

M. Bandini and A. Umani-Ronchi, Catalytic Asymmetric Friedel-Crafts Alkylation, Wiley-VCH, Weinheim, 2009. 

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. 

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

Bandini, M. and Umani-Ronchi, A. (eds) (2009) Catalytic Asymmetric Friedel-Crafts Alkylations, Wiley-VCH Verlag GmbH, Weinheim. 

T. Arai, N. Yokoyama, Angew. Chem. Int. Ed. 2008, 47,4989-4992. Tandem catalytic asymmetric Friedel-Crafts/Henry reaction control of three contiguous acyclic stereocenters. 

Besides performing diastereoselective reactions using chiral staring materials, optically active catalyst-controlled enantioselective Friedel-Crafts alkylation [31] can also be served as an alternative to provide chiral products. Great advances have been demonstrated in this hot field within the last decade. Generally, three strategies have been success-fnlly ntilized to achieve catalytic asymmetric Friedel-Crafts alkylation. The first one involves the nse of chiral Lewis acids, where a chiral ligand is coordinated to the Lewis acid. 

The use of chiral binapthyl-based phosphoric acids (354) in organo-catalytic asymmetric Friedel-Crafts reactions of indoles (352) with enamides and p,y-unsaturated a-keto esters (353), has been studied by Toy and Hermeke (Scheme 93). ... 

Asymmetric synthesis of organofluorine compounds is an important issue in pharmaceutical chemistry 1,2) and optoelectronic material science 3,4). In particular, asymmetric catalysis of carbon-carbon bond-forming reactions is the most attractive method, because the carbon skeleton of chiral organofluorine molecules can be constructed at the time of asymmetric induction 5-10). The Friedel-Crafts (F-C) reaction is one of the most fundamental carbon-carbon bondforming reactions in organic synthesis 11-14). However, its application to catalytic asymmetric synthesis has been quite limited (diastereoselective 25-22, enantioselective 23-25, stereospecific 2d,2. Herein, we report the catalytic... 

Two years after the discovery of the first asymmetric Br0nsted acid-catalyzed Friedel-Crafts alkylation, the You group extended this transformation to the use of indoles as heteroaromatic nucleophiles (Scheme 11). iV-Sulfonylated aldimines 28 are activated with the help of catalytic amounts of BINOL phosphate (5)-3k (10 mol%, R = 1-naphthyl) for the reaction with unprotected indoles 29 to provide 3-indolyl amines 30 in good yields (56-94%) together with excellent enantioselec-tivities (58 to >99% ee) [21], Antilla and coworkers demonstrated that A-benzoyl-protected aldimines can be employed as electrophiles for the addition of iV-benzylated indoles with similar efficiencies [22]. Both protocols tolerate several aryl imines and a variety of substituents at the indole moiety. In addition, one example of the use of an aliphatic imine (56%, 58% ee) was presented. 

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. 

Quallich and Woodall described the first asymmetric synthesis utilizing a catalytic enantioselective reduction of the ketoester 35 with (S)-terahydro-l-methyl-3,3-diphenyl-lH,3W-pyrrolo[l,2-c][l,3.2]oxazaborole (CBS) to give the desired hydroxyester 36 (90% ee). After mesylation, Sn2 displacement with a higher-order cuprate derived from copper cyanide gave the diaryl r-butyl ester 37 with good chirality transfer. Intramolecular Friedel-Crafts cyclization gave the tetralone 31 in 90% ee (Scheme 7). ... 

The intramolecular C-H insertion reaction of phenyldiazoacetates on cyclohexadiene, utilizing the catalyst Rh2(S-DOSP)4, leads to the asymmetric synthesis of diarylacetates (Scheme 8). Utilizing the phenyl di azoacetate 38 and cyclohexadiene, the C-H insertion product 39 was produced in 59% yield and 99% ee. Oxidative aromatization of 39 with DDQ followed by catalytic hydrogenation gave the diarylester 40 in 96% ee. Ester hydrolysis followed by intramolecular Friedel-Crafts gave the tetralone 31 (96% ee) and represents a formal synthesis of sertraline (5). Later studies utilized the catalyst on a pyridine functionalized highly cross-linked polystyrene resin. ... 

Uraguchi D, Sorimachi K, Terada M (2004) Organocatalytic asymmetric aza-Friedel-Crafts alkylation of furan. J Am Chem Soc 126 11804-11805 Uraguchi D, Terada M (2004) Chiral Brpnsted acid-catalyzed direct Mannich reactions via electrophilic activation. J Am Chem Soc 126 5356-5357 Vachal P, Jacobsen EN (2000) Enantioselective catalytic addition of HCN to ketoimines. Catalytic synthesis of quaternary amino acids. Org Lett 2 867-870... 

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