Aromatic compounds asymmetric activation

Enolate Alkylations with Transition Metal Coordinated Electrophiles. Coordination of various transition metals to dienes and aromatic compounds sufficiently activates these compounds to nucleophilic addition, resulting in high asymmetric induction at the a-center. However, the manganese complexes of various benzene derivatives couple with lithium enolates in low selectivity at the nascent stereogenic center on the ring (eq 15). ... 

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). 

The hydrocarbon 25 has been partially resolved by asymmetric complexation with Newman s reagent [TAPA ( )-a(2,4,5,7-tetranitro-9-fluorenylideneaminooxy)prop-ionic acid] thereby establishing its chiral Z)2-structure 53). Similarity, the naphthaleno-phane 27b could be resolved by chromatography on silicagel coated with (—)-TAPA 49) and recently also by HPLC on optically active poly(triphenylmethyl methacrylate)49a) which also proved to be very useful for the optical resolution of many other axial and planarchiral aromatic compounds 49b>. 

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. 

On the basis of Betti s initial work, the Betti reaction has been extended to both primary amines and secondary amines. The resulting Betti amines have been applied as ligands or chiral auxiliaries in asymmetric synthesis. In addition, the Betti reaction has also been extended to the reaction among aldehydes, secondary amines, and compounds of active methylene moiety, such as dibenzyl ketones which can tautomerize to enols and mimic naphthol. Moreover, the reaction of aromatic aldoximes and 0-keto esters to afford isoxazolones should also be considered as an extension of the Betti reaction. 

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 F-C reactions of aromatic compounds can provide a practical synthetic route for chiral a-trifluorobenzylalcohols of synthetic importance (Scheme 1). In previous asymmetric syntheses of a-trifluorobenzylalcohols, the asymmetric reductions of trifluoromethyl ketone were used as a key step 30-34). In this F-C reaction, the catalytic activity and enantioselectivity of BINOL-Ti catalysts (55-57) were found to be critically influenced by the substituents of BINOL derivatives (Table I). 1) (i )-6,6 -Br2-BINOL-Ti catalyst was the most effective catalyst. This F-C reaction did not proceed easily as compared with the carbonyl-ene reaction (7,8) or the Mukaiyama-aldol reaction (7) with fluoral. Therefore, the role of the electron-witiidrawing group at the 6,6 -position of BINOL is very important for increasing the Lewis acidity (runs 1 3). Relatively high enantio-... 

Table II The F-C reactions of aromatic compounds with fluoral catalyzed by (i )-6,6 -Bn-BINOL-Ti complex through asymmetric activation.

Triethylaluminum can be economically prepared on an industrial scale from aluminum hydride and ethylene,124 so a successful alkylation using organo-aluminum compound will certainly open up a new area for active research. Asymmetric alkylation of aromatic aldehydes with triethylaluminum was carried out by Chan et al.125 In the presence of (R)- or (.S )-134 and Ti(OPr1)4, alkylation proceeded readily, yielding the alcohol with high ee (Scheme 2-52). 

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). 

Peroxidases have been used very frequently during the last ten years as biocatalysts in asymmetric synthesis. The transformation of a broad spectrum of substrates by these enzymes leads to valuable compounds for the asymmetric synthesis of natural products and biologically active molecules. Peroxidases catalyze regioselective hydroxylation of phenols and halogenation of olefins. Furthermore, they catalyze the epoxidation of olefins and the sulfoxidation of alkyl aryl sulfides in high enantioselectivities, as well as the asymmetric reduction of racemic hydroperoxides. The less selective oxidative coupHng of various phenols and aromatic amines by peroxidases provides a convenient access to dimeric, oligomeric and polymeric products for industrial applications. 

Two main attributes are ascribed to natural shikimic acid the first, of practical nature, is related to its use as a chiral source for asymmetric synthesis, the second, of biochemical prominence, is connected to the key role it exerts in the production of benzenoid rings of natural aromatic amino acids and other important metabolites [45]. The biological relevance of shikimic acid and the challenging nature of its multichiral structure have motivated an active search for the development of viable asymmetric syntheses of this compound and novel structural variants [46],... 

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