Highly substituted aromatic compounds

Application of l,n-ADEQUATE for highly substituted aromatic compounds... 

This [2+2 + 2]cycloaddition is useful for synthesis of highly substituted aromatic compounds since substitution reactions with arenes are seldom regiospecific. An example is the synthesis of calomelanolactone (2) from triyne l.5... 

The present overview deals with the application of Fischer chromium carbene complexes in the benzannulation reaction for the preparation of highly substituted aromatic compounds. Before focussing on specific arenes (Section 8.5), details of the mechanism are given (Section 8.2), and the scope and limitations of the reaction are defined (Section 8.3). A short description of the experimental procedure is given thereafter (Section 8.4). Finally, the contribution deals with the application of the chromium carbene benzannulation to natural compounds and molecules with biological activity (Section 8.6). 

Sterically congested thiophene 1,1-dioxides are less prone to dimerization the most stable is the tetrachlorothio-phene 1,1-dioxide. Other congested thiophenedioxides such as 3,4-di-/-butyl, 3,4-diadamantyl, and 3,4-dineo-pentylthiophene 1,1-dioxide undergo [4-1-2] cycloaddition with electrophilic dienophiles followed by SO2 extrusion to produce highly substituted aromatic compounds (Scheme 30) <1998JOC4912>. 

An analogous vinylketene intermediate (127, see Schemes 57 and 59) as proposed for the Dotz reaction has been assumed in the so-called cyclobutenedione methodology [161]. The key intermediate is a 4-aryl or 4-alkenyl substituted 2-cyclobutenone (128) that can be obtained e.g. by the reaction of the 3-cyclo-butene-1,2-dione (129) with the appropriate lithium reagent or Stille coupling with 4-chloro-3-cyclobutenone. Thermal cyclobutenone ring opening to the vinylketene 130 followed by electrocyclization furnishes the highly substituted aromatic compound 131 (see Scheme 59). 

In independent research Danheiser and coworkers applied the reaction of siloxyalkynes with cyclobutenones to the synthesis of various highly substituted aromatic compounds 47 (equation 31). 

Danheiser and coworkers have developed a convenient synthetic approach to useful, highly substituted, aromatic compounds by the reaction of alkoxyacetylenes with cyclobutenone derivatives (equation 61) . The mechanism of this annulation is similar to the analogous reaction of siloxyacetylenes (equation 31, Section II.D.2) and the key step is a [2+2] cycloaddition of alkoxyacetylene with a vinylketene intermediate. ... 

The steric limitations for this rearrangement are illustrated by the spectra of the two highly substituted aromatic compounds that follow. With one ortho methyl group, the rearrangement proceeds to give a peak at mk 120, but if both ortho positions are substituted, the reaction is blocked (Equation 2.64). 

Similarly, 1,3-dienic 5-sultone 112 can be used for the synthesis of highly substituted aromatic compound 113 by a domino DA/rDA process [99]. 

The most common types of aryl halides m nucleophilic aromatic substitutions are those that bear o ox p nitro substituents Among other classes of reactive aryl halides a few merit special consideration One class includes highly fluormated aromatic compounds such as hexafluorobenzene which undergoes substitution of one of its fluorines on reac tion with nucleophiles such as sodium methoxide... 

The para-fluorine atoms on highly fluorinated aromatic compounds such as hexafluorobenzene or decafluorobiphenyl are activated and thus can go through aromatic nucleophilic substitution with bisphenols in an aprotic solvent at low temperatures (<80°C).121 123... 

Kerogens isolated from the Fig Tree cherts produced very complex mixtures of pyrolysis products, dominated by a series of methyl branched alkenes with each member of the series having 3 carbon atoms more than the previous member. At each carbon number a highly complex mixture of branched alkanes and alkenes plus various substituted aromatic compounds was found. The highly branched structures may have actually incorporated isoprenoids originally present in the Precambrian microorganisms (Philp Van DeMent, 1983)6>. 

Tetraalkyllead compounds tend to be clear, colorless liquids and are soluble in common organic solvents, such as hydrocarbons, chloroform and ether. The tetraaryl derivatives are beautifully crystalline solids most are white or colorless, but the more highly substituted phenyllead compounds tend to be yellow in color. The tetraaryl derivatives tend to be soluble in chloroform, acetone and aromatic hydrocarbons, and insoluble in such solvents as ether, alcohol and aliphatic hydrocarbons. 

Traditionally, nitration has been performed with a mixture of nitric and sulfuric acids (mixed acid method). However, the method is highly unselective for nitration of substituted aromatic compounds and disposal of the spent acid reagents presents a serious environmental issue. In order to address these problems several alternative methods for aromatic nitration have been developed recently. For example, lanthanide triflates catalyse nitration with nitric acid, which avoids the use of large volumes of sulfuric acid but provides no enhancement of selectivity.6 Selectivity of nitrations with alkyl nitrates,7 acyl nitrates,8 or even nitric acid itself9,10 can, however, be enhanced by zeolites. 

Although its oxidizing power is not very high, the superoxide radical is able to degrade substituted aromatic compounds with high absorption in the UV range. 

Thallium(ni) reagents are useful for mediating electrophilic substitutions. The resnlting arylthalhum dications are converted into substituted aromatic compounds easily and in high yields. The new substituent enters the aromatic ring at the position in which the TfX2 group was attached (equation 29). 

The Birch reduction of aromatic hydrocarbons and ethers to the 2,5-dihydro derivatives proceeds most satisfactorily when the substitution pattern allows the addition of hydrogen to two unsubstituted positions in a para relationship. If this requirement is satisfied, better yields are obtained from more highly substituted aromatic rings than from (say) anisole itself, which affords a substantial amount (20%) of 1-methoxycyclohexene (c/. Scheme 1). Extra substitution presumably hinders protonation at the terminus of the dienyl anion (which would lead to a conjugated diene and overreduction). The utilization of anisole moieties as precursors to cyclohexenones has been of very limited value with many 1,2,3-substitution patterns and more densely substituted derivatives. Compounds (23) to (26), for example, have only been reduced by employing massive excesses (200-600 equiv.) of lithium metal,2 while the aromatic ring in (28) is completely resistant to reduction. ... 

The interaction of certain electrophiles with an aromatic ring leads to substitution. These electrophilic reactions involve a carbocation intermediate that gives up a stable, positively charged species (usually a proton) to a base to regenerate the aromatic ring. Typical electrophiles include chlorine and bromine (activated by interaction with a Lewis acid for all but highly reactive aromatic compounds), nitronium ion, SO3, the complexes of acid halides and anhydrides with Lewis acids (see Example 4.5) or the cations formed when such complexes decompose (R— —O or Ar =0), and carbocations. 

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