Regiocontrol regioselectivity

Substituted TMM complexes also cycloadd to aldehydes in the presence of a tin cocatalyst such as MesSnOAc and MesSnOTs [31]. Reaction of 2-heptenal with methyl precursor (6) gave a mixture of methylenetetrahydrofurans (68) and (69). This regioselectivity is reversed with 10-undecenal and methyl precursor (5), where adduct (70) now predominates over (71). As in the carbocyclic system, the phenylthio group also functions as a regiocontrol element in reaction with cyclohexyl aldehyde. The initially formed adduct (72) eliminates the element of thio-phenol on attempted allyl rearrangement, and the overall process becomes a cycloaddition approach to furans (Scheme 2.21) [20]. 

The major problem remains control of regioselectivity in favor of the branched regioisomer. While aryl alkenes as well as heteroatom-substituted alkenes favor the chiral branched isomer, for aliphatic alkenes such an intrinsic element of regiocontrol is not available. As a matter of fact branched-selective and asymmetric hydroformylation of aliphatic alkenes stands as an unsolved problem. In this respect regio- and enantioselective hydroformy-... 

Albeit nitrile oxides are more regioselective than nitrones towards MCP, in cycloadditions with alkylidenecyclopropanes they show a lower regiocontrol than nitrones. The same trend, however, on passing from electron-donating to electron-withdrawing substituents is observed. Benzylidenecyclopropane (156) gives (entry 1, Table 28) only a 1 4 mixture (compared with 1 19 with nitrone... 

Regioselectivities that are usually high to excellent have been reported in novel palladium-catalyzed Heck arylation reactions with a variety of allylic substrates. The //-stabilizing effect of silicon enhanced regiocontrol in the internal arylation of allyl-trimethylsilane (Eq. 11.5) [18], and coordination between palladium and nitrogen... 

Having established that pure enantiomer ( S,ZR)-77 was capable of undergoing remarkably regioselective and diastereoselective C-H activation, it followed that highly efficient enantiomeric differentiation of rac-77 could be accomplished.199 Hence, the Rh2(5Y-MEPY)4-catalyzed reaction of rac-77 effectively gave close to a 1 1 mixture of enantioenriched (lY)-78 (91% ee) and ( R)-79 (98% ee) (Equation (68)). Other equally spectacular examples of diastereo- and regiocontrol via chiral rhodium carboxamide catalysts in cyclic and acyclic diazoacetate systems have been reported.152 199 200 203-205... 

This excellent regiocontrol was exploited by subjecting terminal alkenes and hydroxyalkynoates to ruthenium catalysis conditions to afford butenolides and pentenolides (Equation (23)).36 The Alder-ene reaction occurs preferentially to form the G-G bond at the alpha-carbon of the alkynoate. The unusually high regioselectivity is attributed to a synergistic effect derived from an enhanced coordination of the hydroxyl group to the ruthenium. 

Palladium complexes are general and versatile catalysts for allylic amination.1,la lh The palladium-catalyzed allylic aminations of 1,3-symmetrically disubstituted substrates, including enantioselective versions, have been widely studied.1, a h It has been important to control the regioselectivity in allylic amination of unsymmetrical substrates 1 or 2 (Equation (1)). In general, palladium-catalyzed allylic amination gives the ( )-linear product 3Tla lh regiocontrol in amination has recently attracted much attention in approaches toward the branched product 4. 

It was shown that the protonation regioselectivity was strongly controlled by methoxy and hydroxyl substituents, whose directive effects overwhelmed the methyl substitution effects." Regiocontrol by —OMe and —OH substituents, and its stronger influence relative to methyl groups, was also observed in the nitration and bromination reactions (Fig. 21). Regioselectivities observed in the nitration and bromination reactions in representative cases were the same as those via protonations. 

Finally, steric effects have an important influence on regioselectivity. This is very clearly demonstrated, for example, in the case of allyl carbanions substituted with silyl groups16. Therefore, despite wide investigation of this topic17, understanding of regiocontrol is still very poor, due to the complexity of the situation. 

In cases where more than one carbon-carbon double bond is present in the molecule, the possibility of selective cyclopropanation of one of them arises. Regiocontrol in intermole-cular cyclopropanation of substituted dienes has been the subject of much investigation and considerable differences can occur, depending on the structure of the substrate, catalyst and the carbene substituents. With a 1-substituted terminal diene such as 120, cyclopropanation, in general, occurs at the less-substituted double bond (equation 108)22 26,3, 16U62. In this case, the nature of the catalyst and of the carbenoid precursors are less important in determining the regioselectivity. 

A few examples are available in which regiocontrol in the cyclopropanation of non-conjugated diene is catalyst-dependent. An early example is showed in equation 118. Copper(II) triflate catalysed cyclopropanation of diene 132 with diazomethane occurs preferentially at the less substituted double bond, whereas copper(II) acetylacetonate in contrast promotes cyclopropanation at the more substituted double bond (equation 118)13. Regiocontrol in the cyclopropanation of norbornene derivative 133 is strongly catalyst-dependent (equation 119). When diphenyldiazomethane is used as carbenoid precursor, the regioselectivity of this cyclopropanation is significantly enhanced165. 

Regiocontrol in intramolecular cyclopropanation is mainly dependent on the site of the unsaturated centre related to the carbenoid centre. In other words, ring size of the bicyclic or polycyclic systems which derive from the cyclopropanation is the key to regiocontrol of this type of reaction. The regioselectivity is independent of the catalyst employed, Five-membered ring formation is favoured over the production of six- or seven-membered rings... 

The opposite regioselectivity observed for the addition of methylbutenyltin to similar allyl substrates (equations 241 and 242),137>139 caused by the presence of maleic anhydride in the latter case (equation 242), may be viewed as support for a change in mechanism when the electron deficient alkene ligand is present. Conversely, both reactions could proceed by metal addition, with the regiocontrol exercised by the maleic anhydride acting in the addition-reductive elimination sequence. 

The relationship between regioselectivity and acid-base effects in the cyclization of carboxylic acids with a pendant triple bond has been systematically investigated both experimentally and with the density functional theory calculations. Regiocontrolled cyclizations by acid or base catalyst has been developed [(21) (22) or (23)].39... 

Regiocontrol in these useful reactions is achieved by a careful selection of alkylation or acylation reagent, base, nucleophile, solvent, and reaction temperature. Reactions of oxyazolium salts are useful for regioselective introduction of substituents both at ring positions and at lateral positions. The alkylation or acylation followed by reaction with nucleophile, base, or... 

The regioselective synthesis can be carried out in the limits of only electrochemical synthesis. In these transformations, the nature of metal complex-former (material of the anode) and of donor atom X (N, O) are the main regiocontrolling factors forming, for instance (4.38), the coordination sphere of the chelates 864 and 865 [119] ... 

Regioselective hydroformylation. The rhodium-catalyzed hydroformylation of (Z)-f-butyldiphenylsilylalkenes is an excellent route to p-silyl aldehydes (equation I). A bulky silyl group is essential for this regiocontrol. 

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