Regioselectivity of the reaction

Jaeger and co-workers studied the regioselectivity of the reaction of a surfactant diene with a surfactant dienophile in micellar media" ". The orientational effects in the aggregates could result in an increase in the regjoselectivity in aqueous solutions of these compounds as compared to the reaction in organic media. 

The regioselectivity of the reaction appears to be determined by a balance of electronic and steric factors. For acrylate and propiolate esters, the carb-oxylate group is found preferentially at C3 of the carbazole product[6-8]. Interestingly, a 4-methyl substituent seems to reinforce the preference for the EW group to appear at C3 (compare Entries 4 and 5 in Table 16.2). For disubstituted acetylenic dicnophiles, there is a preference for the EW group to be at C2 of the carbazole ring[6]. This is reinforced by additional steric bulk in the other substituent[6,9]. 

The reaction conditions (neutral, acidic or basic) do have an affect on the regioselectivity of the reaction. Acidic reaction conditions have also been shown to preferentially provide one regioisomer over basic conditions for reactions of aryl hydrazines. Extensive studies with 2-perfluoroacylcycloalkanones and mono-substituted hydrazines were studied to determine the selectivity of various alkyl-, aryl-, and heteroaryl-substituted hydrazines. Reactions of the aryl hydrazine 21 with the trifluoromethyl-substituted cycloalkanone 22 under neutral conditions (methanol, reflux) gave a mixture of isomers 23 and 24, whereas the reaction of the pyridyl hydrazine 25 was shown to give exclusively 26. 

Diethylamino-4-(4-methoxyphenyl)-isothiazole 5,5-dioxide 6 is (95T(51)2455) a highly reactive partner in 1,3-dipolar cycloadditions with several dipoles. Azomethine yhdes, such as oxazolones 7 and miinchnones 8, afforded with 6 bicychc pyrrolo[3,4-d]isothiazole 5,5-dioxides 9, 10, 11 in satisfactory yield. The regioselectivity of the reaction was excellent. The thermal behavior of these new bicychc systems was investigated. When heated at their melting point or shghtly above, triarylpyrroles 12, 13 were obtained through SOj and AtiV-diethylcyanamide ehmination. 

The regioselectivity of the reaction with unsymmetrical alkynes is poor. Mixtures of isomers are obtained with alkyl substituted acetylenes, if the alkyl groups do not differ much in size. A solution to this problem has been reported by Semmelhack et al. The reactants are connected by a -OCHaCHaO-tether, which can later be removed the coupling step thus becomes intramolecular ... 

The regioselectivities of the reactions of EDG-substituted alkenes are determined by delocalization from R to E via If. The delocalization contains the cychc interactions of orbitals, i.e., the electron-donating orbital (edg) of EDG, electron-accepting orbital (e ) of the electrophile, and the bonding n orbital and the antibonding n orbital. For... 

Phenyl vinyl sulfones reacted with cyclohexanone enamines 332 to afford adducts which, upon hydrolysis, gave 2-(2-phenylsulfonyl)alkylcyclohexanone 333a . However, in the reaction with phenyl styryl sulfone, two products 333b and 334 were obtained by the nucleophilic attack at the and a-carbon atoms . Steric effects, electrostatic interactions between the nitrogen atom of the enamine and the oxygen atoms of the sulfone group, and medium effects contribute to the regioselectivity of the reaction. ... 

Scheme 2.165. Influence of pressure on the regioselectivity of the reaction of 2-751 in dichloromethane at 90°C.

A-chloro carboxamides can also be used as nitrogen sources, but the reaction must be performed at 4 °C or below to avoid Hofmann degradation of the carboxamides. The regioselectivity of the reaction is dependent on the ligand and the solvent used PHAL and AQN ligands again show opposite selectivity to each other (Scheme 57).204 The aminohydroxylation using... 

The solvomercuration of alkenes has been exhaustively studied and is now well understood. The mechanism of this reaction proceeds through two steps coordination of the mercuric ion to the alkene to form a fluxional cationic intermediate and subsequent nucleophilic anti-attack. Charge stabilization of the cationic intermediate constitutes one of the factors dictating the regioselectivity of the reaction (Scheme 11). 

In contrast with the results of Langa et al. on the cydoaddition reaction to C70, MW irradiation had no effect on the regioselectivity of the reactions in polar solvents, but a substantial effect was observed both in the nonpolar solvent, xylene and under solvent-free conditions. In polar solvents (pentanol and DMF) the ratio of products 64, 65, and 66 was 95 5 0 under both MW and conventional heating. In xylene and in the absence of solvent the ratio of isomers changed from 32 28 40 (xylene) and 36 27 27 (no solvent) under conventional heating to 100 0 0, i. e. totally regioselec-tive, under MW activation. 

In the nineteen-nineties, numerous examples of 1,3-dipolar cycloadditions under microwave heating were reported with a wide variety of dipoles. In many cases the product yields and/or reaction times were improved and the method was used to prepare valuable compounds that could not be obtained by classical heating and, in some instances, the regioselectivity of the reaction was modified. Most of these processes were performed in the absence of solvent. 

Oxidative ring opening of isoxazolidines leads to nitrones. Thus, bicyclic isox-azolidines (50) and (51), treated with m-CPBA, afford nitrones (52), (53), (54), and (55) (Scheme 2.19). Conformational analysis has confirmed the key role of the nitrogen lone pair with respect to regioselectivity of the reaction and of the intramolecular kinetic deprotonation of the intermediate oxoammonium derivative (125). 

In this context, alkynes have been investigated under carbometallation conditions in order to generate tri- or tetrasubstituted alkenes with very good stereochemical control.46 For the unactivated triple bonds, the major issue is the regioselectivity of the reaction. 

Some attack at the terminal carbon of the alkyne also takes place, and the regioselectivity of the reaction depends very much on the steric bulk of the alkyne substituents. 

Similar models explain the 1,8-, 1,10- and 1,12-addition reactions to the extended Michael acceptors 91, 93 and 95, respectively (Schemes 2.32 and 2.33). Again, these transformations start with the formation of a cuprate Jt-complex at the double bond neighbouring the acceptor group [61a]. Subsequently, an equilibrating mixture of a-copper(III) intermediates is presumably formed and the regioselectivity of the reaction may then be governed by the different relative rates of the reductive elimination step of these intermediates. Consequently, the exclusive formation of allenic prod-... 

The hydroformylation reaction that converts olefins into aldehydes is the largest volume homogeneous transition-metal catalyzed reaction used today. This reaction has been extensively studied and nowadays a number of efficient catalysts make it possible to control the regioselectivity of the reaction to give terminal or internal aldehydes (Scheme 1). 

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