Regiochemistry of the

Effects of substituent on the regiochemistry of the 5-hexenyl radical cyclization... 

For intramolecular D-A rxns, geometric constraints can now reverse the normal regiochemistry of the addition as compared to the intermolecular rxn. 

Shape selective catalysts, such as ZeoHtes of the H-ZSM-5 type, are capable of directing alkyl groups preferentially to the para position (18). The ratio of the catalyst to the substrate also plays a role ia controlling the regiochemistry of the alkylations. For example, selective alkylation of anilines at the para position is achieved usiag alkylatiag ageats and AlCl ia equimolar ratio (19). 

Excellent yields of the former product are also obtained with quinoline N-oxide. Improved yields of Reissert compounds are found under phase-transfer conditions (29). The regiochemistry of the method changes dramatically with /V-alkyl quin olinium salts, eg, /V-methy1quino1inium iodide [3947-76-0] (12), which form 4-cyanoquinoline [23395-72-4] (13) (30), through the intermediary in this example of A[-methyl-4-cyano-l,4-dihydroquinoline... 

Normally, phenylhydrazine reacts with the enol form of 1,1,1-trifluorometh-ylpentane-2,4-dione to give 5-methyl-l-phenyl-3-tnfluoromethylpyrazole as the major product. However, the use of pyrrolidine as a transient carbonyl-blocking group can completely reverse the regiochemistry of the addition and leads to 3-methyl-l-phenyl-5-trifluoromethylpyrazole [102] (equation 88)... 

Phenylmercury halides give the corresponding phenylmercury derivative, CgH5HgC(CF3)3 (61%) [156], and perfluorocyclobutene gives the corresponding cyclobutyl derivative [156], Mechanistically, the reaction could be interpreted as formation of the fluorocarbanion via nucleophilic addition of fluoride ion to the fluoroolefin followed by capture of the intermediate fluorocarbanion by the mercury salt [156]. The regiochemistry of the reaction is consistent with this mechanism [156] (equation 119). 

The regiochemistry is determined by the regiochemistry of the fluoride ion addition reaction, that is, via the most stable perfluorocarbanion intermediate Von Werner used a similar reaction to prepare silver compounds from perfluoro-2-methyl-2-butene and perfluoro 2 methyl-2-pentene [271] Silver(I) fluoride adds to bis(ttitluoromethyl)ketene in DMF without fluoride ion catalysis [270] The analogous trifluorovinylsulfurpentafluoride reacts similarly to give the isolable pentafluorosulfur derivative [272] (equation 187)... 

When both a-positions of the oxime possess active hydrogen, the regiochemistry of the Hoch-Campbell reaction prefers the side with more available hydrogens— indicating the process is kinetically controlled. In case of oxime 36, azirine 37 was not formed. Instead, azirine 38 was obtained exclusively. Addition of the third equivalent of the Grignard reagent delivered aziridine 39 as a mixture of two diastereomers. 

Carbo- and heterocyclic nitroarenes react v/ith anions of rerr-butyl and cumyl hydroperoxides in the presence of strong bases to form snbsdtuted o- and -nitrophenols Regiochemistry of the hydtoxyladon can be controlled to a snbstandM extent by selecdon of proper conthdons fEq 9 53 ... 

Steric factors also play an important role in determining the regiochemistry of the dihydroxylation, and the modeling studies appear to show that the C3-C4 double bond is more hindered than the C5-C6 double bond, although this is often a rather subjective... 

Compared to the tungsten-catalyzed reaction, however, the regiochemistry of the molybdenum-catalyzed alkylation is highly dependent on the structure of the nucleophile89. 

The description of the regiochemistry of the cycloaddition products of dienes that have two or more dissimilar substituents may require incorporation of their name in the new notation (Equations 1.18 [38] and 1.19 [39]). 

Tamariz and coworkers [42] have described a versatile, efficient methodology for preparing N-substituted-4,5-dimethylene-2-oxazolidinones 42 (Figure 2.5) from a-diketones and isocyanates and have also studied their reactivity in Diels-Alder reactions. This is a method for synthesizing polycyclic heterocyclic compounds. Some of the reactions of diene 42 are summarized in Scheme 2.18. The nitrogen atom seems to control the regiochemistry of the reaction. 

As an approach to biomimetic catalysis, Sanders and colleagues [67] synthesized a series of 1,1,2-linked cyclic porphyrin trimers that allow the stereo- and regiochemistry of the Diels-Alder reaction of 84 and 85 within the molecular cavity to be controlled, thereby producing prevalently or exclusively the endo 86 or the exo 87 adduct. Two examples are illustrated in Scheme 4.18. At 30 °C and in the absence of 88, the reaction furnishes a mixture of diastereoisomers, while the addition of one equivalent of trimer 88 accelerates the reaction 1000-fold and the thermodynamically more stable exo adduct 87 is the sole detectable product. 

Note that the regiochemistry of the cycloaddition (11) combines the most electrophilie... 

Here is where we get back to mechanisms. Whether we are talking about Zaitsev vs. Hoffman elimination reactions or about Markovnikov vs. anti-Markovnikov addition reactions, the explanation of the regiochemistry for every reaction is contained within the mechanism. If we completely understand the mechanism, then we will understand why the regiochemistry had to be the way it turned out. By understanding the mechanism, we eliminate the need to memorize the regiochemistry for every reaction. With every reaction you encounter, you should consider the regiochemistry of the reaction and look at the mechanism for an explanation of the regiochemistry. 

We know which two groups are adding to the double bond, and we know the regiochemistry of the addition. But in order to draw the products correctly, we also need to know the stereochemistry of the reaction. To better explain this, we will redraw the alkene in a different way. 

When the reaction of 1,1-dimethyl allene with o-BrC6H4SH was carried out in the presence of Pd(OAc)2/dppf/i-Pr2HN/CO in benzene, hydrothiolation of the allene took place (Eq. 7.26) [37]. However, the regiochemistry of the adduct 36 was different from that obtained by the Pd(OAc)2-catalyzed hydrothiolation of mono-substituted allenes (cf. Eq. 7.24), showing that the regiochemistry of the hydrothiolation of allenes can be controlled by the reaction conditions even when the same metal(Pd) catalyst is used. 

Additional coordination upon hydrozirconation (see Scheme 8-13) but also during the subsequent transformations (see Schemes 8-14 and 8-15) has to be taken into account in the analysis of the regiochemistry of the hydrozirconation/trans-metalation reaction sequences. 

The regiochemistry of the hydrozirconation of disubstituted stannyl- [24, 167-170] and silyl- [171] acetylenes and boron- [118, 172-175] and zinc- [34, 126] alkynyl derivatives result in the formation of 1,1-dimetallo compounds. Hydrozirconation of alkynyliodonium salts affords alkenylchlorozirconocenes with the Zr-C bond geminal to the iodonium moiety [176]. These zirconocene complexes allowed the preparation of ( )-trisubstituted olefins (Scheme 8-20). 

Conditions for kinetic control of enolate formation can be applied to the Robinson annulation to control the regiochemistry of the reaction. Entries 5 and 6 of Scheme 2.11 are cases in which the reaction is carried out on a preformed enolate. Kinetic... 

This regiochemistry is consistent with the electrophilic character of Pd(II) in the addition step. Solvent and catalyst composition can affect the regiochemistry of the Wacker reaction. Use of /-butanol as the solvent was found to increase the amount of aldehyde formed from terminal alkenes, and is attributed to the greater steric requirement of /-butanol. Hydrolysis of the enol ether then leads to the aldehyde. 

The regiochemistry of the Heck reaction is determined by the competitive removal of the (3-proton in the elimination step. Mixtures are usually obtained if more than one type of (3-hydrogen is present. Often there is also double-bond migration that occurs by reversible Pd-H elimination-addition sequences. For example, the reaction of cyclopentene with bromobenzene leads to all three possible double-bond isomers.146... 

The hydration of an alkene double bond under strongly acidic conditions is again a classical reaction that involves a carbocation intermediate, which often leads to various competing reaction products.27 The regiochemistry of the water addition follows the Markovnikov rule.28... 

Klingebiel32 observed a related insertion with the silene 131 (Eq. 47), which gave the product 132 under the thermal conditions of its formation. Surprisingly, the regiochemistry of the C—H addition to the Si=C bond was opposite to the case in Eq. (46). 

The nitrogen of the nitro group absorbs at 371 ppm and shows 3-bond correlations from both the aromatic protons flanking the group (7.49 and 7.41 ppm). The common correlation from the former signal to both nitrogens confirms the regiochemistry of the structure. 

Complexes 17-19 can be written in one valence structure as a, /3-unsaturated carbonyl compounds in which the carbonyl oxygen atom is coordinated to a BF2(OR) Lewis acid. The C=C double bonds of such organic systems are activated toward certain reactions, like Diels-Alder additions, and complexes 17-19 show similar chemistry. Complexes 17 and 18 undergo Diels-Alder additions with isoprene, 2,3-dimethyl-1,3-butadiene, tram-2-methyl-l,3-pentadiene, and cyclopentadiene to give Diels-Alder products 20-23 as shown in Scheme 1 for complex 17 (32). Compounds 20-23 are prepared in crude product yields of 75-98% and are isolated as analytically pure solids in yields of 16-66%. The X-ray structure of the isoprene product 20 has been determined and the ORTEP diagram (shown in Fig. 3) reveals the regiochemistry of the Diels-Alder addition. The C-14=C-15 double bond distance is 1.327(4) A, and the... 

Table 10 Regiochemistry of the exclusive and non-stereoselective methoxy-bromide formation in the methanolic bromination of fiwis-a-methylstilbenes, XC6H4C(Me)=CHC6H4Y rate-regioselectivity relationship.0...

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