Regioselectivity substituent effects

More complete interpretations of Diels-Alder regioselectivity have been developed. MO results can be analyzed from an electrostatic perspective by calculating potentials at the various atoms in the diene and dienophile. These results give a more quantitatively accurate estimate of the substituent effects. Diels-Alder regioselectivity can also be accounted for in terms of HSAB theory (see Section 1.2.3). The expectation would be that the most polarizable (softest) atoms would lead to bond formation and that regioselectivity would reflect the best mateh between the diene and dienophile termini. These ideas have been applied using 3-2IG computations. The results are in agreement with the ortho rule for normal-electron-demand Diels-Alder reactions. ... 

Hydroboration is highly regioselective and stereospecific. The boron becomes bonded primarily to the less-substituted carbon atom of the alkene. A combination of steric and electronic effects works to favor this orientation. Borane is an electrophilic reagent. The reaction with substituted styrenes exhibits a weakly negative p value (-0.5).156 Compared with bromination (p+ = -4.3),157 this is a small substituent effect, but it does favor addition of the electrophilic boron at the less-substituted end of the double bond. In contrast to the case of addition of protic acids to alkenes, it is the boron, not the hydrogen, that is the more electrophilic atom. This electronic effect is reinforced by steric factors. Hydroboration is usually done under conditions in which the borane eventually reacts with three alkene molecules to give a trialkylborane. The... 

Stratakis, M., Nencka, R., Rabalakos, C., Adam, W. and Krebs, O. (2002). Thionin-sensitized intrazeolite photooxygenation of trisubstituted alkenes substituent effects on the regioselectivity as probed through isotopic labeling. J. Org. Chem. 67, 8758-8763... 

Stratakis, M., Sofikiti, N., Baskakis, C. and Raptis, C. (2004). Dye-sensitized intrazeolite photooxygenation of 4-substituted cyclohexenes. Remote substituent effects in regioselectivity and diastereoselectivity. Tetrahedron Lett. 45, 5433-5436... 

The reactions of 534 with substituted quinones produced mixtures of regioisomers. The substituent effect on the regioselectivity of the [8 + 2] cycloaddition reactions was said to be dependent on steric as well as electronic effects. Equation 156 shows the reaction between 534 and 2-methylbenzoquinone (539). The reaction afforded a mixture of two regioisomeric adducts 540 and 541, which were transformed to azulenes 542-545 under the reaction conditions applied318. 

The influence of the solvent on the regioselectivity is perfectly described by FMO theory142. As mentioned above, the regioselectivity is determined by orbital coefficients on the terminal carbons of the diene and dienophile which, in turn, are determined by the electronic substituent effects. These can be modified by electron donation or electron withdrawal by the solvent or additives like Lewis acids. 

An inner-sphere electron reduction has been proposed as a possible mechanism for the Fe(II)-induced decomposition of 1,2,4-trioxolanes (ozonides) (75) and (76). Benzoic acid was found to be the major product. The nucleophilic Ee(II) species attack the ozonide from the less hindered side of the electrophilic 0-0 a orbital to generate exclusively the Ee(III) oxy-complexed radical (inner-sphere electron transfer). After selective scission of the C-C bond, the resulting carbon-centred radical produced the observed product. The substituent effect determine the regioselective generation of one of the two possible Fe(III)-complexed oxy radicals. The bond scission shown will occur if R is bulkier than R. ... 

The reaction of 2-vinylfuran la with methyl propiolate (MP) did not proceed at room temperature owing to the lower reactivity of this dieno-phile and at 80°C, although two isomeric benzofurans are possible, only methyl benzofuran-4-carboxylate 6a was obtained. This regioselectivity is not unexpected, considering electronic and substituent effects (67AG 16). 

H. Kamitakahara and F. Nakatsubo, Substituent effect on ring-opening polymerization of regioselectively acylated 1,4-anhydro-a-D-glucopyranose derivatives, Macromolecules, 29 (1996) 1119-1122. 

Various mechanisms for the insertion reaction are conceivable (a) ionic stepwise, (b) radical (chain or nonchain), and (c) concerted. Generally, ionic or radical mechanisms give a mixture of products with cis and trans stereochemistry. In some special cases of the ionic reaction, however, exclusive formation of a trans product has been observed (62, 66). Therefore, stereoselectivity does not necessarily imply a concerted mechanism other evidence, e.g., regioselectivity, kinetic data, solvent effects, and substituent effects, must be sought out. 

Substituent Effects on Reactivity and Regioselectivity of Ar-SE Reactions of Monosubstituted Benzenes... 

Kong, F.F., Zhai, B.C., and Song, Q.-H. (2008) Substituent effects on the regioselective formation of the Patemd-Biichi reaction of 5- or/and-6-methyl substituted uracils with 4,4 -disubstituted benzophenones. Photochemical el Photobiological Sciences, 7, 1332-1336. 

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