Chiral induction, arenes

Intramolecular oxidative cyclizations in the appropriately substituted phenols and phenol ethers provide a powerful tool for the construction of various practically important polycyclic systems. Especially interesting and synthetically useful is the oxidation of the p-substituted phenols 12 with [bis(acyloxy)iodo]-arenes in the presence of an appropriate external or internal nucleophile (Nu) leading to the respective spiro dienones 15 according to Scheme 6. It is assumed that this reaction proceeds via concerted addition-elimination in the intermediate product 13, or via phenoxenium ions 14 [18 - 21]. The recently reported lack of chirality induction in the phenolic oxidation in the presence of dibenzoyltar-taric acid supports the hypothesis that of mechanism proceeding via phenoxenium ions 14 [18]. The o-substituted phenols can be oxidized similarly with the formation of the respective 2,4-cyclohexadienone derivatives. 

It should be mentioned, that larger assemblies consisting of nine calixarenes are available with the calixarene-monocyanurate 139,208a while the double-calixarene 140 forms a double-box with 136 consisting of 15 molecules (3 x 140 and 9 x 136).283 Polymeric aggregates are formed between bis-melamine and bis-cyanurate calix[4]arenes.284 In all these cases, chiral induction still remains to be explored. 

Asymmetric induction may also derive from chirality in the amine part of the enamine. The reaction of the enamine (S)-l-(l-cyclohexenyl)-2-(methoxymethyl)pyrrolidine with ( )-(2-ni-troethenyl)arenes gives, after hydrolysis, a single diastereomeric product in >90% ee30. 

Asymmetric induction of between 30 and 66% has been reported for the addition of perfluoroalkyl iodides to chiral arene/chromiumtricarbonyl complexes using ultraso-nically dispersed zinc at room temperature (Scheme 3.19) [101], Photochemical decomposition of the organometallic intermediate affords a chiral alcohol product. The reaction is carried out in DMF as solvent and high overall yields are reported e.g.80 % (R = Et). Only a small excess of the perfluoroalkyl iodide is required and the conversion is complete in under 1 h. 

Three types of reaction systems have been designed and applied for the enantioposition-selective asymmetric cross-coupling reactions so far. First example is asymmetric induction of planar chirality on chromium-arene complexes [7,8]. T vo chloro-suhstituents in a tricarhonyl("n6-o-dichlorobenzene)chromium are prochiral with respect to the planar chirality of the 7t-arene-metal moiety, thus an enantioposition-selective substitution at one of the two chloro substituents takes place to give a planar chiral monosubstitution product with a minor amount of the disubstitution product. A similar methodology of monosuhstitution can be applicable to the synthesis of axially chiral biaryl molecules from an achiral ditriflate in which the two tri-fluoromethanesulfonyloxy groups are enantiotopic [9-11]. The last example is intramolecular alkylation of alkenyl triflate with one of the enantiotopic alkylboranes, which leads to a chiral cyclic system [12], The structures of the three representative substrates are illustrated in Figure 8F.1. 

Direct nucleophilic addition of potassium enolates derived from bis(trimethylsilyl)ketene acetals to aromatic chromium-complexed aromatic ethers affords meta substituted products (Scheme 124). A very high degree of asymmetric induction is obtained upon reaction of chiral arene chromium tricarbonyl complexes. For example, alkylation of complex (80)gave (81)afterdecomplexation(Scheme 125). ... 

Catalytic asymmetric induction of planar chirality in an (arene)chromium complex has been reported in the cross-coupling of tricarbonyl (o-dichlorobenzene)chromium 30 with vinylic metals, where one of the meso chlorine atoms undergoes the coupling to give the monovinylation product 31 with up to 44% ee (Scheme 2-19) [38]. 

R = Me) hydrolysis of the intermediate affords the 4-hydroxy compound (127 R = OH) in low yield (Equation (14)) <85CJC33I3>. Reaction of the chiral oxathiolanone oxide (128) with TFAA and an arene gives some asymmetric induction in the formation of (129) (Equation (15)) <90TA143>. With the unsubstituted compound (39), Pummerer reaction allows the introduction of a variety of nucleophiles at the 4-position to give (130) and oxidation of the intermediate with pyridine N-oxide affords access to the little known 4,5-dione (35) (Equation (16)) <93JHC663>. 

Kamikawa, K., Harada, K. and Uemura, M. (2005) Catalytic asymmetric induction of planar chirality palladium catalyzed intramolecular Mizoroki-Heck reaction of prochiral (arene)chromium complexes. Tetrahedron Asymmetry, 16, 1419-23. 

In Sj reactions, substrate and reagent combine to form a diastereomeric transition state. In the case of auxiliary-controlled reactions, the asymmetric induction is promoted by a chiral element temporarily linked to the arene or the nucleophile. The ideal chiral auxiliary has to fulfill several requirements (i) it must be easily available in both enantiomeric forms to permit selective synthesis of both enantiomers, (ii) it must induce good stereoselectivity, (iii) the diastereomeric products must be easily separated, and (iv) cleavage of the chiral auxiliary must provide the requisite enantiomer in high yield without racanization. Additionally, an efficient work-up to allow easy recovay of expensive chiral auxiliaries is highly desirable. Most chiral auxiliaries are either natural products (alcohols, amino acids, carbohydrates, etc.) or derived from natural products. 

Arenes suffer dearomatization via cyclopropanation upon reaction with a-diazocarbonyl compounds (Btlchner reaction) [76]. Initially formed norcaradiene products are usually present in equilibrium with cycloheptatrienes formed via electrocyclic cyclopropane ring opening. The reaction is dramatically promoted by transition metal catalysts (usually Cu(I) or Rh(II) complexes) that give metal-stabilized carbenoids upon reaction with diazo compounds. Inter- and intramolecular manifolds are known, and asymmetric variants employing substrate control and chiral transition metal catalysts have been developed [77]. Effective chiral catalysts for intramolecular Buchner reactions include Rh Cmandelate), rhodium carboxamidates, and Cu(I)-bis(oxazolines). While enantioselectivities as high as 95% have been reported, more modest levels of asymmetric induction are typically observed. 

Whereas nucleophilic addition of alkyl-lithium compounds to the optically pure arene(tricarbonyl)chromium complex (8) proceeds without asymmetric induction, the chelates (9) react to give amines (10), after hydrolysis, with optical purity of up to 94%." Replacement of the phenyl groups on the azomethine function by alkyl groups should provide an efficient route to a large number of chiral amines. 

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