Reversal of regioselectivity

The bond highlighted m yellow is the peptide bond ) Pencyclic reaction (Section 10 12) A reaction that proceeds through a cyclic transition state Period (Section 1 1) A honzontal row of the penodic table Peroxide (Section 6 8) A compound of the type ROOR Peroxide effect (Section 6 8) Reversal of regioselectivity oh served m the addition of hydrogen bromide to alkenes brought about by the presence of peroxides m the reaction mixture... 

Peroxide effect (Section 6.8) Reversal of regioselectivity observed in the addition of hydrogen bromide to alkenes brought about by the presence of peroxides in the reaction mixture. 

An intramolecular version of the Diels-Alder reaction with a diene-carboxylate was used by Williams et al. in the synthetic study of the antibiotic ilicicolin H.91 The interesting aspect of this work is that they found that under aqueous conditions, there is an observed reversal of regioselectivity (Eq. 12.31). In toluene, there is a 75 25 ratio of a/b while in degassed water the ratio of a/b is 40 60. 

In view of our earlier statement, that the regioselectivity remains unaffected by the ligands of the catalyzing metal, the reversal of regioselectivity for myrcene (21), when Cu(OTf)2 is replaced by CuS04, comes as a surprise. As the two observations... 

Despite a similar reversal of regioselectivity is also observed in the cycloadditions of diazoalkanes 226, 238, and 231 to methoxycarbonyl methylenecyc-lopropane 4 (Scheme 39), the result cannot be ascribed only to steric effects in this case [61]. A difference in dipolar character of dipoles 226 and 231 is also able to justify the result. 

Aryl or alkyl substituents on the exocyclic double bond steer the regioselec-tivity towards the formation of isoxazolidine-4-spirocyclopropanes 274-276 (Table 22, entries 1-3). A complete reversal of regioselectivity to 277-279 was observed in the reactions of methoxycarbonyl substituted methylenecyclo-... 

Han, L.-B., Hua, R., and Tanaka, M., Phosphinic acid induced reversal of regioselectivity in Pd-catalyzed hydrophosphinylation of alkynes with Ph2P(0)H, Angew. Chem., Int. Ed. Engl, 37, 94, 1998. 

The uncatalyzed hydroboration-oxidation of an alkene usually affords the //-Markovnikov product while the catalyzed version can be induced to produce either Markovnikov or /z/z-Markovnikov products. The regioselectivity obtained with a catalyst has been shown to depend on the ligands attached to the metal and also on the steric and electronic properties of the reacting alkene.69 In the case of monosubstituted alkenes (except for vinylarenes), the anti-Markovnikov alcohol is obtained as the major product in either the presence or absence of a metal catalyst. However, the difference is that the metal-catalyzed reaction with catecholborane proceeds to completion within minutes at room temperature, while extended heating at 90 °C is required for the uncatalyzed transformation.60 It should be noted that there is a reversal of regioselectivity from Markovnikov B-H addition in unfunctionalized terminal olefins to the anti-Markovnikov manner in monosubstituted perfluoroalkenes, both in the achiral and chiral versions.70,71... 

The 1,3-dipolar cycloadditions of benzonitrile oxides with tertiary cinnamides yield the 5-phenyl and 4-phenyl regioisomers in a reversal of the expected regioselectiv-ities shown with methyl cinnamate. Calculations have shown that steric factors are responsible for this reversal of regioselectivity." The 1,3-dipolar cycloadditions of benzonitrile oxide with electron-rich and electron-poor dipolarophiles are accelerated by sodium dodecyl sulfate micelles. Phenyl nitrile ylides react with electron-deficient alkenes to produce five-membered -heterocycles where measured rate constants are between 4 x 10 and 7 x 10 lmoP ... 

The regioselectivity of these ring opening reactions is sensitive to additional annelation on benzene (Table 7). In the tetralin derivative (59), little selectivity between type I and type II products is observed with either set of electrophilic reagents. A reversal of regioselectivity is observed in cyclobutabenzene and indan... 

What factors might lead to the reversal of regioselectivity ... 

By treatment with s-BuLi-TMEDA at —78 °C, unprotected 2-methoxybenzoic acid has been deprotonated exclusively in the position ortho to the carboxylate.58 A reversal of regioselectivity is observed when the acid has been treated with n-BuLi-r-BuOK. These results are of general utility for the one-pot preparation of a variety of very simple 3- and 6-substituted 2-methoxybenzoic acids that are not easily accessible by conventional means. 

Scheme 4.74 complete reversal of regioselectivity is observed when highly basic lithium amides are used as nucleophiles. Activation of the benzylic C-O bond by chelate formation of Li+ with the oxirane and the carbonyl group has been proposed as a possible reason for this unexpected reversal of regioselectivity [332]. 

Table 2 Reversal of regioselectivity with aryl esters...

Other examples are summarized in Table 1. Terminal olefins nicely participated in this reaction as shown in Eq. (1) and entries 1 and 2 in Table 1. Styrene showed a reversal of regioselection relative to the position of the newly formed carbon-magnesium bond. However, sterically hindered olefins afforded an increasing amount of hydrogenated product, even after treatment of the reaction mixture with D2O (see Table 1, entries 3 and 4). Finally, no deuterated hydrocarbons were obtained from trans- and trisubstituted olefins, even though the starting materials were almost completely consumed (see Table 1, entries 5 and 6). 

A complete reversal of regioselectivity was observed by M. Isobe and co-workers during the Larock heteroannulation of o-iodoaniline with a-C-glucosylpropargyl glycine in an attempt to prepare C-glycosyltryptophan. " ... 

Interestingly, use of tetrabutylammonium fluoride instead of Lewis acid resulted in the reversal of regioselectivity and tlie a adduct was obtained preferentially (Scheme 11.8). 

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