Regioselectivity meta-selectivity

A distinct feature of the acenaphthene proton sponge 40 is that the para-positions are already occupied and the nitration may proceed at either the sterically hindered ortho-positions or the poorly activated meta-positions. As noted above (Schemes 22 and 23), the ortho-nitration is complicated by demethylation of one of the NMe2 groups. Still, selective mono-ortao-nitration without demethylation under comparatively mild conditions (tetranitromethane/CCl4/0 °C) has been reported to proceed in a good yield47. Even more important is the possibility to perform a regioselective meta-nitration of compound 40 in sulfuric acid to the derivatives 172-174 (Scheme 29). Obviously, the reaction occurs in this case via the cation 40 H+ 37. 

One of the first eye-catching synthetic applications of arene-chromium chemistry was the synthesis of the sp/ro-sesquiterpenes ( )-acorenone and ( )-acorenone B (rac-7) disclosed by Semmelhack and Yamashita in 1980 [14]. These authors twice exploited the meta-selective nucleophile addition to anisole-Cr(CO)3 derivatives (Scheme 1). Starting from complex rac-1, such a reaction is first used for the regioselective introduction of an acyl sidechain to give 2 after oxidative workup. A few steps later, the nitrile rac-4 (obtained from rac-3 by complexation and separation of the diastereomeric products by preparative HPLC) is deprotonated to form the spiro addition product rac-5, from which the enone rac-6 is obtained after protonation and hydrolysis of the initially formed dienol ether. The final conversion of rac-6 into acorenone B (rac-7) efficiently proceeds over five steps and involves a diastereoselective hydrogenation of an exo-methylene group. 

Subsequent reports showed that a wide range of arene substrates could be borylated, with regioselectivity predominantly dictated by steric factors [77]. In the case of monosubstituted arenes, borylation generally occurs predominantly at the meta and para positions, with a near-statistical ratio while substitution at the ortho position is minor (Scheme 4). In the case of 1,3-disubstituted arenes, borylation occurs exclusively at 5-position. The selectivity was reversed in favor of the ortho position in the case of diethylbenzamide, presumably due to chelation [77]. 

Although mixtures are often obtained, usually one predominates, the one indicated above. This regioselectivity, in which the ortho or para product is favored over the meta, has been explained by molecular-orbital considerations.864 When X = N02, regioselectivity to give the ortho or "para product was very high at room temperature, and this method, combined with subsequent removal of the N02 (see 0-82) has been used to perform regio-selective Diels-Alder reactions.865... 

The series of para-substituted 2-ary 1-1,3-dithianyl carbanions shown in Table 6 and equation (41) are expected to differ in LUMO energy. The phenoxide-substituted anion (entry 1, Table 6 and equation 41) should have higher LUMO relative to, for example, the simple phenyl-substituted anion (entry 6) and gives a greater preponderance of meta substitution due to stronger orbital control. The smooth correlation of selectivity with reactivity for this series of closely related anions is consistent with a simple two-parameter analysis. Other regioselectivity results, such as those with o-alkylanilines (Table 2 and equation 30) and [(indole)Cr(CO)3] also have been analyzed in terms of orbital control and conformational effects.87,88,93... 

Excellent regioselectivity and stereoselectivity has been achieved in each photocycloaddition mode [45 48], Regiochemistry and stereochemistry in the meta process is decided by the orientation of the addends in the exciplex and by stabilization of biradical intermediates having a change transfer (CT) character (6) by the substituents on the arene. Intermolecular meta cycloaddition of arenes with cycloalkenes proceeds with endo selectivity (7) (Scheme 5). In the ortho-process, selectivities can be controlled mainly by the substituents on the reactants. 

Rapid Claisen rearrangement of allyl phenyl ether and meta-substituted derivatives has been reported to occur with poor regioselectivity at 250 °C in dicationic ionic liquids, especially (24).23 Claisen rearrangement of resorcinol allyl ethers (25) was found to have poor regioselectivity under thermal or microwave conditions, but it was further found that selectivity for the 6-substituted product (26) over (27) could be improved to 13 1 using boron trichloride and an appropriately protected ether (25 ... 

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. 

Recent results revealed that the ortho photocycloaddition frequently occurs concomitantly with the meta photocycloaddition even in cases where only meta derivatives are obtained. Especially in the case or electron-donor substituted benzene derivatives, the competitive ortho cycloaddition is less stereo- or regioselective and the resulting products are less stable. Aside the meta adducts as main products, complex mixtures of ortho products or products resulting from rearrangements of these primary photoproducts have been obtained [15,16], Improved separation techniques recently enabled a better characterization of these products. Furthermore, using particular conditions like an acidic reaction medium, the intermediates resulting from ortho photocycloaddition could be transformed selectively in more stable final products [17]. 

Regioselectivity in o-disnbstitnted arenes is often high and nseful. A series of examples is snmmarized in Figure 4. The resonance donor substitnent (OMe) appears to dominate the directing inflnences, favoring addition at the less-hindered position meta to itself Bnt with two identical substituents, the addition is preferred in the adjacent position. For example, with the complex of benzocyclobutene, six carbon nucleophiles were tested and each gave addition exclusively at C-3. With the complex of indan, selective addition at C-3 was observed with dithianyl anions, but cyano-stabilized... 

---