Highly alkylated aromatic substrates

Homolytic alkylation of homocyclic aromatic substrates is of much less interest than homolytic arylation because, in addition to the low selectivity, which also characterizes arylation, yields are usually poor, due to side reactions which compete seriously with the simple substitution reaction. The behavior of nonprotonated heteroaromatic substrates is similar. The case is quite different with protonated heteroaromatic bases because side reactions are eliminated or minimized, yields are generally good, and, above all, the selectivity is very high. Moreover, very versatile and easily available sources of alkyl radicals can be used under simple experimental condition it follows that homolytic alkylation of protonated heteroaromatic bases can be considered one of the main reactions of this class of compounds. 

The reactions also led to high regioselectivity (> 20 1). For alkylated aldehydes unbranched in the a-position, however, low diastereoselectivity (d.r. 1.7 1) and yields of 38% were obtained, although enantioselectivity remained excellent (> 97% ee). Use of aromatic substrates resulted in a d.r. of 1 1 to 1.5 1 only, and the enantioselectivity was in the range 67 to 80% ee [93]. Some representative examples of the L-proline-catalyzed aldol reaction with hydroxyacetone are given in Scheme 6.35. 

Electron-rich aromatic componnds are readily alkylated at room temperature with propargyl complexes to form, after demetallation, 2-propyne-snbstituted aromatic compounds. Depending on the snbstitution pattern of the alkyne complex and the aromatic substrate, alkylation occurs at times with very high regioselectivity. This type of annulation was used in a synthesis of psendoipterosin... 

The results on the effect of temperature, contact time and methanol to toluene ratio on the isomer composition of xylenes on K2.5 salt are given in Table 3. It is seen that selectivity of p-xylene decreases with increase in the temperature whereas the selectivity of m-xylene increases, obviously, due to the isomerization. As contact time increases p-xylene selectivity increases. It is also found that the p-xylene selectivity increases with increasing methanol to toluene ratio. As methanol to toluene ratio increases the catalyst surface will be saturated with more of alkylating species which offers hindrance to the approach of the aromatic substrate and thereby resulting in the preferential alkylation at para position. In conclusion,it may be suggested that high Bronsted acidity is responsible for high para selectivity found in heteropolyoxometallates. 

The conjugate Friedel Crafts alkylation is a powerful strategy for the chemical modification of electron-rich aromatic substrates allowing the building up of complex structures, which is very often the synthetic tool of choice when preparing a highly substituted heterocyclic compound. Developments in... 

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