Alkylation ortho-regioselective

An interesting mthenium-catalyzed ortho alkylation of benzonitriles with tri-ethoxyvinylsilanes has been described by Murai and coworkers [81] (Scheme 19.62). A side-on coordination of the jt-bonded nitrile group was proposed to account for the ortho regioselectivity. 

The Diels-Alder reactions of alkyl-substituted benzoquinones with penta-1,3-diene and isoprene were also studied in aqueous cyclodextrin solutions. Highly enhanced ortho- and mefa-regioselectivities were observed (Eq. 12.11).48... 

The regioselectivity of chlorination and bromination of A,A-dialkylbenzamides in aqueous acetic acid is strongly influenced by the alkyl groups." Ortho and para orientation results fairly selectively from substrates with large alkyl substituents. For example, A(Al-diisopropylbenzamide gives o-, m- and jo-chloro derivatives in the proportion 47 11 42. 

Ortho photocycloadditions of benzene derivatives to maleic anhydride have been tabulated in Table 1. Only the structures of the primary ortho adducts are given, but these are not the isolated adducts They always undergo endo [2 + 4] cycloaddition with maleic anhydride, yielding 1 2 adducts. An interesting feature to be seen from Table 1 is that substituents on the benzene (alkyl, phenyl, or halogen) always turn up at the position most remote from the site of addition. In view of the different nature of these substituents, it seems that steric rather than electronic factors are responsible for this regioselectivity. 

Ir(III) complexes can also be used to catalyze the hydroarylation of olefins [5, 6], The catalyst precursors (acac-0,0)2Ir(Ph)(L) (L= pyridine or H20) and [Ir(w-acac-0,0,C3)(acac-0,0)(acac-C3)]2 have been reported and are depicted in Scheme 3, with representative catalytic reactions. Among these catalyst precursors, (acac-0,0)2Ir(Ph)(H20) has been demonstrated to be the most active system [5], The lin-ear-to-branched ratios observed for Ir(III) catalyzed reactions of a-olefins are remarkably similar to those obtained using TpRu(CO)(NCMe)(Ph). For example, hydrophenylation of propene using 11 r (a-acac- O, O,C ) (acac-O, O) (acac-C3) ]2 as catalyst produces a 1.6 1 ratio of linear propylbenzene to cumene (identical to the ratio observed using the Ru(II) catalyst). Similar to the TpRu(CO)(NCMe)(R) catalysts, the regioselectivity of hydroarylation of ethylene that incorporates monoalkyl arenes produces meta- and para-disubstituted alkyl arenes in approximately 2 1 ratio without observation of ortho-disubstituted products. 

Let us go back to radical brominations (cf. Section 1.7.3). The bromination of alkyl aromatics takes place completely regioselectively only the benzylic position is brominated. The intermediates are the most stable radicals that are available from alkyl aromatics, namely, benzylic radicals. Refluxing ortho-xylene reacts with 2 equiv. of bromine to give one monosubstitution... 

Figure 17.50 shows how a benzyl alkoxide can be reduced in this way. Here, the reduction is part of the synthesis of an alkylated aromatic system. The target molecule contains a primary alkyl group. It is not possible to introduce this alkyl group by way of a Friedel-Crafts alkylation into the ortho-position of anisole in a regioselective fashion and without rearrangements (see Section 5.2.5). 

The pioneering study of ruthenium-catalyzed regioselective alkylation using olefins as an alkylating reagent was reported by Lewis and Smith [24]. The ortho-selective ethylation of phenols with ethylene can be attained with the aid of a ruthenium(II) phosphite complex as a catalyst. This alkylation takes place exclusively at the position ortho to the hydroxyl group, and the corresponding 1 2 addition product is the major product (Eq. 6). The use of potassium phe-noxide is the key in this catalytic reaction. Unfortunately, however, the applicability of this reaction is narrow. Thus, phenol is the only applicable substrate in this reaction. 

Phenols are such good nucleophiles that protonated carbonyl compounds functionalize two phenol molecules. The first phenol molecule is attacked in an Ar-SE reaction by the carboxonium ion formed in an equilibrium reaction. Subsequently, the second equivalent of phenol becomes the substrate of a Friedel-Crafts alkylation. The electrophile is the benzyl cation that is formed from the initially obtained benzyl alcohol and the acid. Protonated acetone is only a weak electrophile for electronic and steric reasons It contains two electron-donating and relatively large methyl groups on the electrophilic C atom. Therefore, it attacks phenol regioselectively in the para and not at all in the less favored ortho position (Figure 5.25). The benzyl cation formed there-... 

Metal-promoted approaches have been investigated for the preparation of indazoles. A copper(II) oxide-catalyzed regioselective synthesis of 1-alkyl- and 1-aryi-1 //-indazoles 25 from ortho-halogenated alkanoylphenones, benzophenones, and arylcarboxylic acids 24 with hydrazines in the presence of potassium carbonate has been developed <07OL525>. A... 

Scheme IS depicts a high yield, general method for specific ortho alkylation of polycyclic aromatic hydrocarbons. In this example, biphenyl is subjected to reductive methylation followed by oxidative rearrangement with trityl tetrafluoroborate to give 2-methylbiphenyl. In unsymmetrical substrates the regioselectivity is poor phenanthrene gives a 3 2 mixture of 4-methyl- and 1-methyl-phenanthrene.

For the chelation-assisted catalytic reaction, Jt-electrons in a nitrile group are able to function as a directing group. The ruthenium-catalyzed alkylation of aromatic nitriles with triethoxyvinylsilane takes place predominantly at the ortho position (Eq. 9.10) [24]. This regioselectivity indicates the possibility of Jt-coordination of the CN group to the ruthenium in the catalytic cycle. 

For the alkylation and alkenylation of C-H bonds, olefins and acetylenes are used as reactants. This type of coupling protocol is not applicable to arylation. Recently, a nitrogen-directed arylation of aromatic C-H bonds, leading to biaryl compounds has been developed. In 2001, Oi demonstrated that ruthenium(II)-phosphine can be used as a catalyst in the regioselective arylation of 2-arylpyridines using aryl halides (Eq. 9.34) [4 ]. The predominant ortho selectivity indicates that the coordination of... 

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