Asymmetric Friedel-Crafts

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

The use of diazodicarboxylates has been recently explored in Cinchona alkaloid catalyzed asymmetric reactions. Jprgensen [50] reported the synthesis of non-biaryl atropisomers via dihydroquinine (DHQ) catalyzed asymmetric Friedel-Crafts ami-nation. Atropisomers are compounds where the chirality is attributed to restricted rotation along a chiral axis rather than stereogenic centers. They are useful key moieties in chiral ligands but syntheses of these substrates are tedious. 

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],... 

Moreover, phosphoric acid (5)-3r (5 mol%, R = SiPhj) bearing a bulky triphe-nylsilyl group turned out to be a suitable catalyst for the asymmetric Friedel-Crafts alkylation of iV-alkyl pyrroles 31 with M-benzoyl-protected aldimines 32 (Scheme 12) [23]. 2-Pyrrolyl amines 33 were obtained in high yields (66-97%) and moderate to high enantioselectivities (42 to >99% ee). 

Thiourea catalyst 139 was also screened in the asymmetric Friedel-Crafts reaction between 2-naphthol trans-nitrostyrene (73% yield 0% ee 18 h in toluene at -20 °C and 10 mol%) [277], in the asymmetric aza-Michael reaction of O-benzyl-hydroxylamine to chalcone (72% conv. 19% ee 72 h in toluene at 20 °C and 20mol% catalyst loading) [293], and in the asymmetric Morita-BayUs-HiUman [176, 177] reaction between cyclohexenecarbaldehyde and 2-cyclohexene-l-one (20% yield 31% ee 46 h at rt and 20mol% DABCO and 139) [310]. In aU these transformations, thiourea 139 proved to be not competitive to the organocatalysts probed for these transformations under identical screening conditions and thus was not employed in the optimized protocols. 

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 Reactions. The activation of glyoxylate esters,trifluoromethyl pyruvate esters, and unsaturated a-ketoesters by catalyst 2 converts these materials into effective electrophiles for asymmetric Friedel-Crafts alkylation reactions with activated arenes (eqs 16 and 17). In fact, bis(triflate) (2) is far superior to tbe bis(hexafluoroantimonate) complex at catalyzing the enantioselective alkylation of benzene derivatives. Aniline and anisole derivatives both give the reaction, as do heterocyclic aromatic compounds such as indole and furan. 

Jorgensen, K. A. Asymmetric Friedel-Crafts reactions Cataiytic enantioselective addition of aromatic and heteroaromatic C-H bonds to activated aikenes, carbonyi compounds, and imines. Synthesis 2003,1117-1125. 

Gothelf, A. S., Hansen, T., Jorgensen, K. A. Studies on aluminum mediated asymmetric Friedel-Crafts hydroxyalkylation reactions of pyridinecarbaldehydes. J. Chem. Soc., Perkin Trans. 1 2001,854-860. 

Asymmetric Friedel-Crafts alkylations, besides affording interesting mechanistic problems, also offer valuable synthetic utility. For example, reaction of benzene with optically active 2-chloro-l-phenyl-propane or 1-chloro-2-phenylpropane in the presence of AICI3 affords good yield (60%) of alkylated product with up to quantitative optical yields (see Scheme 3). ... 

Deng and coworkers also found that the bifunctional quinidine- or quinine-based thioureas 36 and 40 effectively catalyze the asymmetric Friedel-Crafts reaction of indoles with a variety of aromatic and alkyl-substituted aldimine derivatives 159. Both enantiomeric forms of the products 160 were obtained with uniformly high... 

The asymmetric Friedel-Crafts reaction was also studied, but the ee was usually low [8]. 

The asymmetric Friedel-Crafts reaction of trifluoromethyl pyruvate 53 with aromatic compounds is catalyzed by cationic Pd(II) complexes with BINAP or SEGPHOS [184]. The reaction proceeded at -30 °C to afford the product 63 in 89% ee with (S)-BINAP and in 82% ee with (S)-SEGPHOS (Scheme 45). In sharp contrast to the situation of the carbonyl-ene reaction, the BINAP ligand provides higher enantioselectivity than the SEGPHOS ligand. 

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... 

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