Optically active aromatic compounds

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... 

The asymmetric Friedel-Crafts (FC) reaction is one of the most powerful methods to synthesize optically active aromatic compounds and has been included in various enantioselective domino reactions. Arai [32] reported the enantioselective... 

The asymmetric Friedel-Crafts alkylation (FC A) is one of the most powerful organic transformations to synthesize optically active aromatic compounds bearing chiral benzylic carbon centers. Since the first example of organocatalytic FCA reaction reported in 2001, continuous interest in this area has resulted in the development of many effective transformations and publications. It s worthy to note that a few important reviews and books have appeared in the literature [1]. This chapter aims to review the progress in the last decade and is organized on the base of different alkylation reagents employed. 

The last group of optically active aromatic compounds to be mentioned includes those in which chiral groups are linked to the aromatic ring. Compounds of this type are frequently encountered in nature (e.g., alanine, mandelic acid. 

As of now no details of the synthesis of optically active tritiated compounds produced under microwave-enhanced conditions have been published. Another area of considerable interest would be the study of solvent effects on the hydrogenation of aromatic compounds using noble-metal catalysts as considerable data on the thermal reactions is available [52]. Comparison between the microwave and thermal results could then provide useful information on the role of the solvent, not readily available by other means. 

Sulfonic acids are prone to reduction with iodine [7553-56-2] in the presence of triphenylphosphine [603-35-0] to produce the corresponding iodides. This type of reduction is also facile with alkyl sulfonates (16). Aromatic sulfonic acids may also be reduced electrochemicaHy to give the parent arene. However, sulfonic acids, when reduced with iodine and phosphoms [7723-14-0] produce thiols (qv). Amination of sulfonates has also been reported, in which the carbon—sulfur bond is cleaved (17). Ortho-Hthiation of sulfonic acid lithium salts has proven to be a useful technique for organic syntheses, but has Httie commercial importance. Optically active sulfonates have been used in asymmetric syntheses to selectively O-alkylate alcohols and phenols, typically on a laboratory scale. Aromatic sulfonates are cleaved, ie, desulfonated, by uv radiation to give the parent aromatic compound and a coupling product of the aromatic compound, as shown, where Ar represents an aryl group (18). 

Compounds of types (286) and (287) are in tautomeric equilibria with 4- or 5-hydroxyazoles. However, the non-aromatic form is sometimes by far the most stable. Thus oxazolinone derivatives of type (287) have been obtained as optically active forms they undergo racemization at measurable rates with nucleophiles (77AHC(21)175). Reactions of these derivatives are considered under the aromatic tautomer. 

Addition of a hydroxyl group to the aromatic ring of ephedrine as well as changing the substitution on nitrogen leads to a compound whose main activity is to raise blood pressure. Thus, lormation of the Shiff base of the m-hydroxy analog of 30 with bcnzylamine (34), followed by catalytic reduction, yields metar- uiiinol (35). When optically active hydroxyketone is employed in... 

As with the reduction of aldehydes and ketones (16-23), the addition of organometallic compounds to these substrates can be carried out enantioselectively and diastereoselectively. Chiral secondary alcohols have been obtained with high ee values by addition to aromatic aldehydes of Grignard and organolithium compounds in the presence of optically active amino alcohols as ligands. ... 

In Table IV some physical data and spectral characteristics of 6,7-secoberbines are listed. Only methyl corydalate (55) is optically active. Formula 55 presents the spatial structure of this compound, deduced by Nonaka et al. (65) and confirmed by Cushman et al. by both correlation with (+)-mesotetrahydrocorysamine (72) (<5S) and total synthesis (69). It is difficult to find common characteristic features in both the mass and H-NMR spectra of these alkaloids because they differ significantly from each other in their structures. On one hand, corydalic acid methyl ester (55) incorporates a saturated nitrogen heterocycle, while the three aromatic bases (56-58) differ in the character of the side chain nitrogen. For example, in mass fragmentation, ions of the following structures may be ascribed to the most intensive bands in the spectrum of 55 ... 

The production of optically active cyanohydrins, with nitrile and alcohol functional groups that can each be readily derivatized, is an increasingly significant organic synthesis method. Hydroxynitrile lyase (HNL) enzymes have been shown to be very effective biocatalysts for the formation of these compounds from a variety of aldehyde and aliphatic ketone starting materials.Recent work has also expanded the application of HNLs to the asymmetric production of cyanohydrins from aromatic ketones. In particular, commercially available preparations of these enzymes have been utilized for high ee (5)-cyanohydrin synthesis from phenylacetones with a variety of different aromatic substitutions (Figure 8.1). 

A vast array of piperidine containing cores, both natural and synthetic, are of biological and medicinal interest. These heterocyclic scaffolds have been the subjects of considerable synthetic efforts, especially for the construction of optically active compounds. In this context, Khan et al. reported a catalytic bromodi-methylsulfonium bromide (BDMS) three-component reaction of 1,3-dicarbonyls with aromatic aldehydes and aromatic amines for a facile access to highly functionalized piperidines (Scheme 24) [104]. This strategy is an interesting illustration of... 

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