Arenes methoxy-substituted

A subsidiary approach involves nuclear modification of the arylsilanes so obtained. The requisite organometallics can be prepared from aryl halides, or by deprotonation of a suitably activated (c.g. methoxy-substituted) arene. A more specialized route involves cycloaddition between alkynylsilanes and diynes. 

Aryl radical cations generated by electron-transfer processes from methoxy substituted arenes to DCN, tethered by oxygen, nitrogen as well as carbon nucleophile leads to intramolecular cyclizations (Scheme 8.67). The synthetic potentials of... 

A versatile strategy for efficient intramolecular oc-arylation of ketones was achieved by the reaction of silyle enol ethers with PET-generated arene radical cations. This strategy involved one-electron transfer from the excited methoxy-substituted arenes to ground-state DCN [42]. Pandey et al. reported the construction of five- to eight-membered benzannulated as well as benzospiroannulated compounds using this approach (Sch. 20) [42a]. The course of the reaction can be controlled via the silyl enol ether obtained... 

Like cerium(IV), iron(III) salts can oxidize electron-rich centers by single-electron transfer to form radicals [1]. Early applications were developed for the oxidation of aromatic compounds, which undergo C-C bond formation to dimeric products. Because of their electronic properties, methoxy substituted arenes 25 are most reactive. Iron(III) chloride supported on silica gel was the reagent of choice, since inter-and intramolecular coupling products 26 are obtained in excellent yields (Scheme 8)... 

Iodine in combination with [bis(acyloxy)iodo]arenes is a classical reagent combination for the oxidative iodination of aromatic and heteroaromatic compounds [99], A typical iodination procedure involves the treatment of electron-rich arenes with the PhI(OAc)2-iodine system in a mixture of acetic acid and acetic anhydride in the presence of catalytic amounts of concentrated sulfuric acid at room temperature for 15 min [100,101]. A solvent-free, solid state oxidative halogenation of arenes using PhI(OAc)2 as the oxidant has been reported [102]. Alkanes can be directly iodinated by the reaction with the PhI(OAc)2-iodine system in the presence of f-butanol under photochemical or thermal conditions [103]. Several other iodine(in) oxidants, including recyclable hypervalent iodine reagents (Chapter 5), have been used as reagents for oxidative iodination of arenes [104-107]. For example, a mixture of iodine and [bis(trifluoroacetoxy)iodo]benzene in acetonitrile or methanol iodinates the aromatic ring of methoxy substituted alkyl aryl ketones to afford the products of electrophilic mono-iodination in 68-86% yield [107]. 

Decarbonylation of 2-[ F]fluorobenzaldehydes has been used to synthesize labeled arenes with nonactivated substituents, e.g., 4-bromo-[ F]fiuorobenzene from 3-bromo-6-nitrobenzaldehyde (Chakraborty and Kilbourn 1991a). This methodology was also applied to [ Fjfluoroarylketones (Allain-Barbier et al. 1998 Forngren et al. 1998) and to mono- to tetra-methoxy-substituted [ F]fluorobenzenes from the corresponding 2-nitro(methoxy) benzaldehydes (Shen et al. 2009). In the latter study they identified side products, which derived from demethylation of methoxy groups and intramolecular redox processes that reduced the radiochemical yields. 

Fig. 14. Crystal structure of the intra- and extraannular methoxy substituted all-homocalix[5]arene (left side) compared to 38 (right side).

This reaction is straightforward with benzene or symmetrical alkyl or methoxy arenes. Unsymmetrically substituted arenes give rise to regioisomers. The mechanistic proposal for this transformation includes activation of the aryl-halogen bond by Fe(II) via one-electron oxidation of the metal center. The aryl radical species thus formed adds to the arene. Subsequent loss of hydrogen halogenide releases the biaryl under formation of the active Fe(II) catalyst. 

The first report to use diphosphite ligands in the asymmetric hydroformylation of vinyl arenes revealed no asymmetric induction [46]. An important breakthrough came in 1992 when Babin and Whiteker at Union Carbide patented the asymmetric hydroformylation of various alkenes with ee s up to 90%, using bulky diphosphites 2a-c derived from homochiral (2R, 4R)-pentane-2,4-diol (Scheme 4) [17]. Their early results showed that (a) bulky substituents are required at the ortho positions of the biphenyl moieties for good regio- and enantio-selectivity and (b) methoxy substituents in the para positions of the biphenyl moieties always produced better enantio-selectivities than those observed for the corresponding ferf-butyl-substituted analogues. 

Beim Erhitzen von Arylaziden mit Nitroso-benzolen bilden sich Azoxyarene. Brauchbare Ausbeuten werden allerdings nur dann erzielt, wenn das Arylazid einen elektronenspen-denden Substituenten wie Methyl oder Methoxy in para-Stellung tragt. Die Art der Substitution am Nitroso-aren ist ebenfalls bedeutsam, die hochsten Ausbeuten werden mit 4-Dimethylamino-l-nitroso-benzol erzielt. Von den beiden moglichen Azoxy-isomeren... 

Benzylische, allylische und tertiare Nitro-aliphaten lassen sich unter Friedel-Crafts-Be-dingungen mit Zinn(IV)-chlorid als Katalysator in Benzol, Toluol, Methoxy- oder 1,2-Dimethyl-benzol in guten Ausbeuten unter nukleophiler Substitution der Nitro-Gruppe in Alkyl-arene umwandeln4,8 3-5 ... 

RBSctions of Radical Anions With Radicals. The coupling of arene or alkene radical anions with radicals is an important reaction, and one that has significant synthetic potential. For example, radicals formed by nucleophilic capture of radical cations couple with the acceptor radical anion, resulting in (net) aromatic substitution. Thus, the l-methoxy-3-phenylpropyl radical (113 R = H) couples with dicyanobenzene radical anion loss of cyanide ion then generates the substitution product 132.2 + ... 

Firstly, various side reactions result from impurities left in the diazonium tetrafluoroborate (water, sodium nitrite, washing solvents). As already discussed, residual water or alcohols (often used to wash the solid diazonium tetrafluoroborate after filtration) substitute the diazo group in an ionic process to produce phenols or alkoxyarenes as byproducts. Residual alcohol can also lead to arenes through a radical hydrodediazoniation process, especially when electron-withdrawing groups are present, as in 3-fluoro-2-methoxy-5-(methoxyearbonyl)benzenediazo-nium tetrafluoroborate (ArF/ArH 4 1)227 or in 2-methyl-5-nitrobenzenediazonium tetrafluoroborate.240 Such radical phenomena increase when sodium nitrite is present as impurity... 

Since trimethylsilylarenes can be prepared by metallation of the arene followed by treatment with chlorotrimethylsilane, this provides an alternative route into a range of difficult substitution patterns. For example, the ortho/para directing effects of the methoxy groups in 1,3-dimethoxybenzene 75 direct the electrophile to the 4-position. However, lithiation of 1,3-dimethoxybenzene takes place at the 2-position. Reaction with chlorotrimethylsilane then gives the 2-trimethylsilyl compound 76, which undergoes ipso substitution with the electrophile to give the 1,2,3-trisubstituted product 77 (equation 39)101,102. 

Remember from Section 12.16 that it is the more activating substituent that determines the regioselectivity of electrophilic aromatic substitution when an arene bears two different substituents. Methoxy is a strongly activating substituent fluorine is slightly deactivating. Friedel-Crafts acylation takes place at the position para to the methoxy group. 

Ohashi et al. [128] found that the yields of ortho photoaddition of acrylonitrile and methacrylonitrile to benzene and that of acrylonitrile to toluene are considerable increased when zinc(II) chloride is present in the solution. This was ascribed to increased electron affinity of (meth)acrylonitrile by complex formation with ZnCl2 and it confirmed the occurrence of charge transfer during ortho photocycloaddition. This was further explored by investigating solvent effects on ortho additions of acceptor olefins and donor arenes [136,139], Irradiation of anisole and acrylonitrile in acetonitrile at 254 nm yielded a mixture of stereoisomers of l-methoxy-8-cyanobicyclo[4.2.0]octa-2,4-diene as a major product. A similar reaction occurred in ethyl acetate. However, irradiation of a mixture of anisole and acrylonitrile in methanol under similar conditions gave the substitution products 4-methoxy-a-methylbenzeneacetonitrile (49%) and 2-methoxy-a-methylbenzeneacetonitrile (10%) solely (Scheme 43). 

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