Directing effects monosubstituted

The positions of the most favourable monosubstitution in attack by nucleophiles are shown in Figure 9.35 for various systems it is clear that directing effects by F have a major influence on the orientation of attack. 

Here mechanisms are essentially arynic with a very strong amino meta-directing effect. Taking into account what we saw about monosubstitutions and the two reactions of Scheme 26, it is easy to understand the results described in Scheme 2747 ... 

In 2008, Blechert et al. reported the total synthesis of e/jt-lepadin F (89) and G (90) by a tandem ene-yne-ene RCM [74]. Lepadins are members of marine alkaloids with decahydroquinoline framework. As a key step in their synthesis (Fig. 26) they planned to construct the decahydroquinoline core skeleton by a selective tandem ene-yne-ene RCM of the dienyne precursor (91). Craiceivably, two different reaction pathways could be expected (1) initiation of metathesis may occur at the terminal double bond followed by two consecutive RCMs to afford the desired 6/6 bicycle (92) or (2) initiation may occur on the disubstituted alkene followed by tandem RCMs to produce the undesired 5/7 bicycle (93). Considering the preference of initiation on monosubstituted double bond as well as the directing effect of free hydroxyl group, pathway (1) may be more favored. Gratilyingly, treatment of dienyne (91) with 10 mol% Gmbbs I catalyst smoothly provided the desired 6/6 bicycle (92) in 90% yield. 

Reich and Cram 8 > studied the patterns of electrophilic substitution of the monosubstituted [2.2]paracyclophanes. It was at once clear that the directive influences of the substituents X (see below) could not be correlated with transannular resonance effects in the ground state 84>. The product pattern predicted on the basis of electrostatic ground-state models, such as the canonical structures 65 for electron-releasing and 66... 

The regioselectivity of nitrone cycloadditions is usually effected by both steric and electronic factors. In nitrone cycloadditions of monosubstituted electron-deficient alkenes under thermal conditions, electronic control steers the nitrone oxygen to the (3-carbon of acceptor, whereas steric factors direct it to the a-carbon. Accordingly, a mixture of two regioisomers is produced under thermal conditions, as shown in Scheme 11.44 for dimethyl 2-oxo-3-butenylphosphonate. With Ti(0 i-Pr)2Cl2, which coordinates in a bidentate chelated fashion with this dipolarophile, only the 4-acyl regioisomer is produced (158). 

Even for a series with varying aromatic substituents, the correlations with deviate significantly from linearity. Typical behavior is illustrated with data for monosubstituted triarylmethyl cations in Figure 1.2. Significant deviations are observed in the points for the para n donors. Moreover, these deviations are in the direction that indicates that these substituents have kinetic stabilizing effects greater than indicated by ct+. In fact, there are good correlations with a parameter based on NMR chemical shifts of benzylic-type cations obtained under stable ion conditions. 

Direct fluorination, therefore, is not particularly effective for the preparation of mono-fluorinated aromatic compounds from monosubstituted precursors since, in these cases, electrophilic fluorination gives mixtures of isomeric products. However, when there are two or more groups in the aromatic substrate which activate the same carbon atom towards electrophilic attack, as in the case of 4-fluorobenzoic acid (Table 5), then direct fluorination is an efficient method for the preparation of fluoroaromatic compounds (Fig. 57) [148]. 

Partially proton-exchanged Na faujasite X, in turn, is the best catalyst for selective monochlorination with tert-butyl hypochlorite.258 NaX, NaY, and NaKL zeolites used in the chlorination of toluene with sulfuryl chloride undergo rapid deactivation because of the accumulation of polychlorinated toluenes in the pores of the catalysts and dealumination.259, 260 Direct electrophilic fluorination of aromatics can be effected by using Selectfluor in the presence of triflic acid.261 Electrophilic fluorination may also be carried out by R2NF and R3N+FA reagents.262 Elemental fluorine may also act as a powerful electrophile in acidic media (sulfuric acid, trifluoroacetic acid, or formic acid), but monosubstituted aromatics give isomeric mixtures.263-265... 

The orientation and reactivity effects of substituents discussed for the substitution of monosubstituted benzenes also hold for disubstituted benzenes, except that the directing influences now come from two groups. Qualitatively, the effects of the two substituents are additive on the reactivity. We therefore would expect 4-nitromethylbenzene to be less reactive than methylbenzene... 

Monosubstitution of the free amine may be achieved by using a less reactive electrophile. Thus aniline and o-toluidine may be mono-iodinated (Expt 6.60) by treatment with iodine (in the presence of sodium hydrogen carbonate or calcium carbonate to remove the liberated hydrogen iodide), the substituent entering the position para to the amino group. Direct iodination can also be effected by using the more powerfully electrophilic reagent, iodine monochloride... 

Following Hrovat et al.,57 we consider the Cope transition state to be a resonance structure of the limiting forms A and B (see p. 218). Synergy is then expected for substitutions at positions 1, 3, 4 and 6, which all favor B, and for substitutions at positions 2 and 5, which favor A. For 1,3-, 1,4-, 2,5-, 3,3- and 3,4-disubstitutions, the net effect should be larger than the sum of monosubstitution effects. Most probably 1,4-disubstitution weakens the 3-4 bond more than 1,3-disubstitution (the two substituents, one direct, the other a vinylogue, are both borne by atom 3). 

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