1,2,3,5-tetrasubstituted benzene

Upon treatment with suitable cobalt complexes, methylbutynol cyclizes to a 1,2,4-substituted benzene. Nickel complexes give the 1,3,5-isomer (196), sometimes accompanied by linear polymer (25) or a mixture of tetrasubstituted cyclooctatetraenes (26). 

Bis(diamino)alanes (R2N)2A1H were used for the hydroalumination of terminal and internal alkenes [18, 19]. TiCb and CpjTiCb are suitable catalysts for these reactions, whereas CpjZrCb exhibits low catalytic activity. The hydroaluminations are carried out in benzene or THF soluhon at elevated temperatures (60°C). Internal linear cis- and trans-alkenes are converted into n-alkylalanes via an isomerization process. Cycloalkenes give only moderate yields tri- and tetrasubstituted double bonds are inert. Hydroaluminahon of conjugated dienes like butadiene and 1,3-hexa-diene proceeds with only poor selechvity. The structure of the hydroaluminahon product of 1,5-hexadiene depends on the solvent used. While in benzene cyclization is observed, the reaction carried out in THF yields linear products (Scheme 2-10). 

A similar strategy has been applied by Mazik and coworkers. The receptor is usually titrated with increasing amounts of the sugar, to evidence binding, to extract the values of the binding constants and to get the stoichiometry of the complexes formed. Reverse titrations and extraction experiments can also be performed. The structures of the receptors described are based on different scaffolds the above mentioned hexasubstituted tripodal benzene moiety and 3,3, 5,5 -tetrasubstituted... 

Similar explanations almost certainly account for the very large effective molarities found for lactonization of the hydroxy acids B.1.13, B.2.16 and B.2.25 (Table 12). All these compounds have the basic tetrasubstituted ethylene (here o-phenylene) structure found in the dialkylmaleic acid system further destabilized by substituents in the 3 and 6 positions of the benzene ring which also act to prevent bond angle spreading of the two inner substituents. (The effects of 3- and 6-substituents on this type of cyclization reaction are well known, and are shown for example by the range of EM s for compounds... 

Following this work on NMR spectra of ozonides, there is an extensive paper by the Griesbaum group" where 35 ozonides (6-14 with different stereochemistries) have been studied. The widely different structures examined allowed the influences of structural features on "O NMR spectra of ozonides to be shown. Five structurally different types of ozonides can be recognized symmetrically tetrasubstituted (type 6), unsymmetrically tetrasubstituted (type 7), unsymmetrically tri- and tetrasubstituted (type 8), unsymmetrically disubstituted (type 9-13) and bicyclic ozonides (type 14). "O NMR chemical shifts of peroxidic and ethereal oxygens are collected in Table 3. All spectra were obtained at natural isotopic abundance, in benzene-dg solution mainly at 25 °C, although in some cases higher temperatures had to be used. These experimental conditions make for an easy comparison with the previously discussed data. 

Finally, an unorthodox pathway to the dithiin systems has been reported Tetracyanoethylene 214 combines with two molecules of thiobenzophenone in refluxing benzene to give the tetrasubstituted 1,2-dithiins 215. However, these were obtained only in addition to the corresponding thiophenes 216 as the main reaction products (Scheme 59) <1985TL1849, 1997LA1677>. 

The structures of the compounds were verified by H NMR spectroscopy. Two doublets of benzene ring protons (7 = 9 Hz) characteristic of mutual ott, ti-positions indicated angularly ring-fused structures. The shifts of NMR peaks and the features of the IR spectra (containing deformed out-of-plane vibrations at 800 cm ) were characteristic of 1,2,3,4-tetrasubstitution and so also confirmed the angular ring fusion. 

Hydrozirconation usually takes place readily at or slightly above room temperature, in benzene or toluene. The reactivity pattern of alkenes in hydrozirconation is the same as in hydroboration, except that tetrasubstituted alkenes are unreac-tive.457,460 A unique feature of hydrozirconation of alkenes is that, with some exceptions, terminally zirconated addition products are formed exclusively. Since isomeric alkenes cannot be isolated, zirconium moves rapidly along the chain without dissociation. Tertiary zirconium intermediates seem to be so unstable that the isopropylidene group never undergoes hydrozirconation [Eq. (6.75)],460 and hence, 1-methylcyclohexene fails to react.460 The reason is apparently steric, since the alkene must fit into the somewhat bent sandwich structure of the reagent (41) ... 

Interestingly, cyclopropane and benzene have the same number of isomers for a given number of identical substituents ignoring optical isomers, cyclopropane and benzene have one type of monosubstituted derivative, three types of disubstituted, three types of trisubstituted, three types of tetrasubstituted and one type apiece of penta- and hexasubstitution. But does this seemingly accidental counting equivalence have any thermochemical consequences ... 

Complex polyfunctional molecules can often be assembled efficiently by short, spectacular sequences of reactions, an example of which is the preparation of the pentasubstituted benzofuran 1. Thus, addition of l-lithio-l-methoxy-3-(trimethylsilyl)-l,2-hexadiene to 3,4-dimethoxycyclobut-3-ene-l,2-dione gave the expected keto alcohol in 70% yield. This alcohol was heated at reflux temperature in toluene for 4 hours to give a 2,3,5,6-tetrasubstituted hydroquinone in 90% yield. Oxidation of the hydroquinone with silver oxide and potassium carbonate in anhydrous benzene (90%) followed by reaction of the quinone thus obtained with TFA in methylene chloride at 0°C then at room temperature for two days gave 1 in 75% yield. 

Although the mechanism of the transformation of single into double bonds has not been investigated in detail, a heteroatom attached to the single bond is necessary for an efficient introduction of the double bond. Trisubstituted pyrazo-lines 46 can be oxidized with (diacetoxyiodo)benzene 3 to the corresponding pyrazoles 47 in good yields [98]. Two double bonds can be introduced in easy accessible proline derivatives 48 [99] by an oxidative decarboxylation with [bis(trifluoroacetoxy)iodo]benzene 4 yielding tetrasubstituted pyrroles of type 49, Scheme 22 [100]. 

To conclude this section on proton transfer, we have examined an alternative mechanism to that of von Grotthuss for proton conduction [105-110], We carried out B3LYP/6-31+G and PW91 DFT calculations on model compounds (1,2,3,4-tetrasubstituted benzenes, e.g., 99) showing that these compounds could play the role of proton conductors [104],... 

A highly chemo- and regioselective [2 + 2 + 2] sequential cycloaddition of alkynes and 1,3-butadiynes catalyzed by Pd(0) complexes as an elegant de novo synthesis of tetrasubstituted benzenes 216 (Scheme 88) and pen-... 

Scheme 88 Tetrasubstituted benzenes by sequential cycloaddition of alkynes [157]...

The ketone could be reduced to two epimeric alcohols dihydro-kopsine-A (CLXXII) resulted with sodium borohydride reduction (100, 109), whereas catalytic hydrogenation gave dihydrokopsine-B (CLXXIV, 100, 104). Both formed only a monoacetate. Kopsine shows no vinyl absorption in the NMR-spectrum and could not be further reduced (except by catalytic hydrogenation of the benzene ring). The molecule therefore contains seven rings, since subsequent evidence excludes a tetrasubstituted double bond. 

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