Arene stereoselectivity

In calix[4]arenes, when the substituent at the lower rim is larger than ethyl, the conformational interconversion among these structures does not occur and it is possible to isolate the four stereoisomers/ Synthetic protocols for the selective functionalization of the OH groups of calix[4]arenes (regioselective alkylation) and for the selective synthesis of certain stereoisomers of tetraalkoxy calix[4]arenes stereoselective alkylation) have been developed." ... 

Synthetic utility of stereoselective alkylations in natural product chemistry is exemplified by the preparation of optically active 2-arylglycine esters (38). Chirally specific a-amino acids with methoxyaryl groups attached to the a-carbon were prepared by reaction of the dimethyl ether of a chiral bis-lactam derivative with methoxy arenes. Using SnCl as the Lewis acid, enantioselectivities ranging from 65 to 95% were obtained. 

Although details vary for particular cases, a common synthetic route to diol epoxides such as (30) frequently begins with the ketone (33) (78MI50700). The final epoxidation is often highly stereoselective. A general route to non-K-region arene oxides has been described (75JA3185). 

Dissociation of phosphite from the dihydride (57), prior to reaction with the arene, is thought to give the nondetected intermediate r)1-C3H5CoH2L—tj4-C6H6 (58), and then the sequence shown accounts for the stereoselectivity. NMR evidence was presented for 57, which also decomposes mainly according to reaction (78) in the absence of arene,... 

The synthesis of the macrocycles 43 (Scheme 9) is an example of repetitive, highly stereoselective Diels-Alder reaction between bis-dienes 41 and bis-dienophiles 42, containing all oxo or methano bridges syn to one another. The consecutive inter- and intramolecular Diels-Alder reactions only succeed at high pressure. Obviously, both reactions are accelerated by pressure. The macrocycles are of interest in supramolecular chemistry (host-guest chemistry) because of their well-defined cavities with different sizes depending on the arene spacer-units. 

A similar intramolecular alkylation of arene-ene substrates is catalyzed by RuGl3/AgOTf, providing good to excellent yields of cyclization products (chromanes, tetralins, terpenoids, and dihydrocoumarins).25 This method is applied to the synthesis of tricyclic terpenoids, which are formed in nearly quantitative yields with high stereoselectivities (trans cis various between 99 1 and 99 2), as shown in Equation (24). 

Substituting deuterium for hydrogen gas in the reduction of BT to DHBT with the catalyst precursor [Rh(NCMe)3(Cp )](BF4)2 has shown that the stereoselective ds-deuteration of the double bond is kinetically controlled by the tj2-C,C coordination of BT. The incorporation of deuterium in the 2- and 3-positions of unreacted substrate and in the 7-position of DHBT has been interpreted in terms of reversible double-bond reduction and arene-ring activation, respectively (Scheme 16.14) [55]. 

Foureman GL, Hernandez O, Bhatia A, et al. The stereoselectivity of four hepatic glutathione S-transferases purified from a marine elasmobranch (Raja erinacea) with several K-region polycyclic arene oxide substrates. Biochim Biophys Acta 1987 914(2) 127-135. 

The microsomal epoxide hydrolases (microsomal EH, mEH), predominantly found in the endoplasmic reticulum, regio- and stereoselectively catalyze the hydration of both alkene and arene oxides, including oxides of polycyclic aromatic hydrocarbons. These enzymes have been purified to homogeneity from various species and tissues [22] [41 - 46], The human microsomal EH contains 455 amino acids (Mr 52.5 kDa) and is the product of the EPHX1 gene [47] (also known as HYL1 [48]). 

In a further development of the norbornene/anihne OHA reaction, Salzer and coworkers used planar chiral arene-chromium-tricarbonyl-based diphosphines for the in situ formation of cis-trans mixtures of complexes 9 and 10 that gave enanti-oselectivities of 51% and 70%, respectively, at 333 K and with a 40-fold excess of naked fluoride , but activities were very low. In the same paper complex 6 was shown to be superior in both activity and enantioselectivity (64% ee) to the corresponding Josiphos compound 5 [15]. The activated N-H bond of benzamide was also stereoselectively added across the double bond of norbornene to afford N-benzoyl-e%o-aminonorbornane in up to 50% yield and 73% ee in the presence of 0.5mol% [IrCl((R)-MeO-bipheb)]2 at 373 K [16]. 

In the approach of Puddephatt et al., the P-phenyl-phosphonitocavitand 2 was obtained by the reaction of phenylphosphonous chloride on re-sorc[4]arene lb (1, R=CH2CH2C6H5) in presence of pyridine as base. The reaction is stereoselective and yielded the bowl-shaped molecule 2 with the four P-phenyl groups directed outwards and the four lone pairs directed inwards ini configuration) [45-49] (Scheme 6). Molecular mechanics calculations performed on the six possible isomers of 2, showed that the iiii isomer is preferred and the orientation of one phenyl group toward the macrocyclic cavity is probable iiio isomer), but two or more phenyl groups oriented inwards are highly unlikely [48]. 

Following this strategy, the stereoselective synthesis of the HU stereoisomer of novel tetra-phosphonatocavitands having lower rim functionality has been reported [66, 67]. Cavitands 12c-12f were respectively synthesized from functionalized resorc[4]arenes Ic-lf. The addition of 1-decanethiol to 12f in the presence of 9-borabicyclo[3.3.1]nonane (9-BBN) in THF afforded cavitand 12g in 80 % yield (Scheme 15). 

The use of thiophosphonic chloride reagent did not give clear results and more importantly, the stereoselectivity of the reaction is difficult to control. For instance, the reaction of C6H5P(S)Cl2 with the resorc[4]arene Ic afforded a mixture of isomers of 13, which have been only partially purified by col-... 

Cacciapaglia, R., Mandolini, L., Arnecke, R., Rohmer, V. and Vogt, W. (1998) Ba(II) complexes of calixcrowns derived from p-tert-butylcalix[5]arene as potential transacylation catalysts. Regio- and stereoselective monoacylation of the calixcrown. J. Chem. Soc., Perkin Trans., 2, 419. 

Some rhodium complexes are more promising in the hydrogenation of arenes. The pentamethylcyclopentadienyl rhodium complex [ RhCUCi -CsMes) ], for instance, is stereoselective in the reduction of CgD6, yielding the all-m product almost exclusively, without the formation of cyclohexene.179... 

Aromatics. A new generation of homogeneous arene hydrogenation catalysts was developed by Rothwell and coworkers. These are hydride derivatives of niobium and tantalum with bulky ancillary aryloxide ligands (see, i.e., 43) exhibiting high regio- and stereoselectivities 467... 

NR = nonreactive toward hydrocarbons PO = oxidation of phosphines to phosphine oxides MF — peroxometallacyclic adduct formation with cyanoalkenes NSE — nonstereoselective epoxidation SE=stereoselective epoxidation AE = asymmetric epoxidation HA- hydroxylation of alkanes HB=hydroxylation of arenes OA = oxidation of alcohols to carbonyl compounds K = ketonization of Lermina 1 alkenes SO oxidation of S02 to coordinated S04 MO = metallaozonide formation with carbonyl compounds I = oxidation of isocyanides to isocyanates. 

The first example of syn stereoselective expoxidation of arene dihydrodiols was reported in 1981.11 The trans-dihydrodiols 11 and 12, when treated with a 10-fold excess of MCPBA in tetrahydrofuran (THF) at room temperature, gave stereoselectively the syn-diol epoxides 13 and 14, respectively. This stereoselectivity has been ascribed to the operation of steric control by the axial benzylic hydroxy group the equatorial hydroxy group does not exert such control. The isomeric 9,10-epoxides of 7,8-dihydroxy-7,8-dihydro-benzo[a]pyrene can be prepared by the same method.12... 

A regioselective and highly syn-stereoselective catalyst-free intermolecular alkylation of aryl borates with aryl epoxides under mild, neutral conditions has been reported.27 The reaction of /ra .s-stilbene oxide with tri(3,5-dimethylphenyl)borate gave a 38% yield (>95% syn) of the C-alkylated product (13), easily separated from (g) the O-alkylated product(s). Triflic anhydride has been used to activate enones to nucleophilic attack by electron-rich arenes in the presence of a sterically hindered base.28 Resorcinol dimethyl ether, for example, reacted with cyclohex-2-en-l-one to... 

A review of catalytic protocols for the ring-closing alkylation and alkenylation reactions of arenes has appeared.33 Recent enantioselective strategies are covered and it is noted that the development of effective catalytic systems for practical stereoselective alkylations remains a challenge. 

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