Cyclohexadienyl cation substitution

If the Lewis base ( Y ) had acted as a nucleophile and bonded to carbon the prod uct would have been a nonaromatic cyclohexadiene derivative Addition and substitution products arise by alternative reaction paths of a cyclohexadienyl cation Substitution occurs preferentially because there is a substantial driving force favoring rearomatization Figure 12 1 is a potential energy diagram describing the general mechanism of electrophilic aromatic substitution For electrophilic aromatic substitution reactions to... 

Figure 12 3 adapts the general mechanism of electrophilic aromatic substitution to the nitration of benzene The first step is rate determining m it benzene reacts with nitro mum ion to give the cyclohexadienyl cation intermediate In the second step the aro maticity of the ring is restored by loss of a proton from the cyclohexadienyl cation... 

Complexation of bromine with iron(III) bromide makes bromine more elec trophilic and it attacks benzene to give a cyclohexadienyl intermediate as shown m step 1 of the mechanism (Figure 12 6) In step 2 as m nitration and sulfonation loss of a proton from the cyclohexadienyl cation is rapid and gives the product of electrophilic aromatic substitution... 

Why IS there such a marked difference between methyl and trifluoromethyl substituents m their influence on electrophilic aromatic substitution s Methyl is activating and ortho para directing trifluoromethyl is deactivating and meta directing The first point to remember is that the regioselectivity of substitution is set once the cyclohexadienyl cation intermediate is formed If we can explain why... 

Sections How substituents control rate and regioselectivity m electrophilic aro 12 10-12 14 matic substitution results from their effect on carbocation stability An electron releasing substituent stabilizes the cyclohexadienyl cation inter mediates corresponding to ortho and para attack more than meta... 

Arenium ion (Section 12 2) The carbocation intermediate formed by attack of an electrophile on an aromatic substrate in electrophilic aromatic substitution See cyclohexadienyl cation... 

Cyclohexadienyl cation (Section 12 2) The key intermediate in electrophilic aromatic substitution reactions It is repre sented by the general structure... 

Substituted aromatics, eg, aLkylbenzenes, sometimes experience attack at the substituent position by NO/ (7). A cyclohexadienyl cation is formed it is unstable and the nitro group migrates on the ring to a carbon atom that is attached to a hydrogen. Loss of the proton results in a stable nitroaromatic. 

In order for a substitution to occur, a n-complex must be formed. The term a-complex is used to describe an intermediate in which the carbon at the site of substitution is bonded to both the electrophile and the hydrogen that is displaced. As the term implies, a a bond is formed at the site of substitution. The intermediate is a cyclohexadienyl cation. Its fundamental structural characteristics can be described in simple MO terms. The a-complex is a four-7t-electron delocalized system that is electronically equivalent to a pentadienyl cation (Fig. 10.1). There is no longer cyclic conjugation. The LUMO has nodes at C-2 and C-4 of the pentadienyl structure, and these positions correspond to the positions meta to the site of substitution on the aromatic ring. As a result, the positive chargex)f the cation is located at the positions ortho and para to the site of substitution. 

If the transition state resembles the intermediate n-complex, the structure involved is a substituted cyclohexadienyl cation. The electrophile has localized one pair of electrons to form the new a bond. The Hiickel orbitals are those shown for the pentadienyl system in Fig. 10.1. A substituent can stabilize the cation by electron donation. The LUMO is 1/13. This orbital has its highest coefficients at carbons 1, 3, and 5 of the pentadienyl system. These are the positions which are ortho and para to the position occupied by the electrophile. Electron-donor substituents at the 2- and 4-positions will stabilize the system much less because of the nodes at these carbons in the LUMO. 

When we exanine the cyclohexadienyl cation intermediates involved in the nitration of (trifluoromethyl)benzene, we find that those leading to ortho and para substitution ar e strongly destabilized. 

After what we have seen to date, it surely comes as no great surprise to find that the ratio of o- to p-product obtained from substitution of C6H5Y, where Y is o-/p-directing, is seldom, if ever, the statistical ratio of 2 1. There is found to be very close agreement between calculation and n.m.r. data for the distribution of +ve charge—p-> o- m—around the ring in the cyclohexadienyl cation (57), which is the Wheland intermediate for proton exchange in benzene (cf. p. 133) ... 

The iron-mediated construction of the carbazole framework proceeds via consecutive C-C and C-N bond formation as key steps [70,71]. The C-C bond formation is achieved by electrophilic substitution of the arylamine with a tricarbonyliron-coordinated cyclohexadienyl cation. The parent iron complex salt for electrophilic substitutions, tricarbonyl[/j -cyclohexadienylium] iron tetrafluoroborate 6a, is readily available by azadiene-catalyzed complexation and subsequent hydride abstraction (Scheme 9). 

The two key steps for the construction of the carbazole framework by the iron-mediated approach are, first, C-C bond formation by electrophilic aromatic substitution of the arylamine with the tricarbonyliron-complexed cyclohexadienyl cation and, second, C-N bond formation and aromatization by an oxidative cyclization. Application of this methodology provides murrayanine (9) and koenoline (8) in three steps and 15%, and in four steps and 14% overall yield, respectively, starting from the commercial nitroaryl derivative 601 (573,574) (Scheme 5.33). 

The total synthesis of carbazomycin D (263) was completed using the quinone imine cyclization route as described for the total synthesis of carbazomycin A (261) (see Scheme 5.86). Electrophilic substitution of the arylamine 780a by reaction with the complex salt 779 provided the iron complex 800. Using different grades of manganese dioxide, the oxidative cyclization of complex 800 was achieved in a two-step sequence to afford the tricarbonyliron complexes 801 (38%) and 802 (4%). By a subsequent proton-catalyzed isomerization, the 8-methoxy isomer 802 could be quantitatively transformed to the 6-methoxy isomer 801 due to the regio-directing effect of the 2-methoxy substituent of the intermediate cyclohexadienyl cation. Demetalation of complex 801 with trimethylamine N-oxide, followed by O-methylation of the intermediate 3-hydroxycarbazole derivative, provided carbazomycin D (263) (five steps and 23% overall yield based on 779) (611) (Scheme 5.91). 

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