Meta-substitution, regioselective formation

Palladium-catalysed directed C-H oxidation with (diacetoxy)iodobenzene of a series of meta -substituted aryl pyridine and aryl amide derivatives resulted in the formation of the corresponding acetoxy compounds. The reactions generally proceed with high levels of regioselectivity for functionalization of the less sterically hindered ortho-C-H bond.144 The mechanism shown in Scheme 4 has been proposed for the oxidation of 2,6-dimethylphenol with (diacetoxyiodo)benzene for the formation of 3,5,3, 5 -tetramethyl-biphenyl-4,4 -diol, via C-C coupling.145... 

This transition metal-free approach proceeded under very mild conditions and was typically regioselective for the formation of the meta-substituted product. It was noted that the amount of halogenation was dependent upon the acid used in the reaction. Changing from TFA to acetic acid resulted in sluggish reactivity, while sulfuric acid resulted in moderate conversion into the monobrominated product along with the formation of the dibrominated species (10%). In related work, the use of NBS in concentrated sulfuric acid effectively brominated a series of deactivated arenes [124]. One difference between the two approaches was that the latter was a bit more effective for the bromination of benzoic acid derivatives (Scheme 7.72). These approaches are complementary and are effective solutions for moderately deactivated systems, provided that the substrates do not contain functional groups that are sensitive to the acidic conditions. 

Butadienes with alkyl substituents in the 2-position favor the formation of the so-called para-products (Figure 15.25, X = H) in their reactions with acceptor-substituted dienophiles. The so-called mefa-product is formed in smaller amounts. This regioselectivity increases if the dienophile carries two geminal acceptors (Figure 15.25, X = CN). 2-Phenyl-1,3-butadiene exhibits a higher para -selectivity in its reactions with every unsymmetrical dienophile than any 2-alkyl-1,3-butadiene does. This is even more true for 2-methoxy- 1,3-butadiene and 2-(trimethylsilyloxy)-l,3-butadiene. Equation 15.2, which describes the stabilization of the transition states of Diels-Alder reactions in terms of the frontier orbitals, also explains the para "/"meta "-orientation. The numerators of both fractions assume different values depending on the orientation, while the denominators are independent of the orientation. 

---