Cationic manifold

Vinylcyclopropanes represent particularly useful functionality. They do permit a ring expansion to cyclobutanes via the cyclopropylcarbinyl cation manifold (Eq. 9). Equally important, such systems suffer smooth thermal rearrangement to cyclopen-... 

The analogous Z aryl triflate 19.1 reacts under the cationic manifold to give, ultimately, oxindole (/ )-17.3a in 72% yield and 43-48% ee (Scheme 8G.19) [38]. An important synthetic advance is the observation that Heck cyclization of this substrate could be diverted to the more selective neutral pathway by addition of halide salts. For example, Heck cyclization of triflate 19.1 in the presence of 1 equiv. of n-Bu4NI gave (/ )-17.3a in 62% yield and 90% ee, which is similar to the enantioselectivity obtained for cyclization of the corresponding iodide 18.1c under neutral conditions (see entry 6, Table 8G, 1). Conversely, cyclization of iodide 18.1c in the... 

In reactions that proceed via the cationic manifold (164 - 165 v 166 -> 167 - 168) the alkene can bind to the metal and undergo Heck reaction while both phosphines remain bound to palladium. In most cases, reactions that proceed via the cationic pathway provide better enantioselectivity, presumably because the ligand maintains two points of contact to the metal during the entire carbon-carbon bond-formation process. 

When the substrate is a triflate, or when a halide is subjected to appropriate reaction conditions in the presence of a halide scavenger (such as silver or thallium salts), the reaction proceeds via the cationic manifold. After oxidative addition, dissociation of X yields cationic intermediate 67. Alkene coordination provides 68 and migratory insertion delivers 69. /S-Hydride elimination then yields the desired product 66. Of importance in the pathway 62- 7— 68— 69— 66 is that both phosphines maintain contact with the metal throughout the process. This is ostensibly the factor responsible for the high enantioselectivities observed for reactions that are thought to proceed along this pathway. This contrasts with the course of events in the neutral pathway, where phosphine dissociation is thought to be responsible for low enantioselectivities. 

An example of the use of an intermolecular carbopalladation in complex molecule synthesis is the preparation of a PAF (platelet activating factor) antagonist (Scheme 11). In the key step, an intermolecular Heck reaction of 2-naphthyl triflate with 2,3-dihydrofuran 71 yields 2-naphthyl-2,3-dihydrofuran 72 in 52% yield with excellent enantioselectivity. The reaction presumably occurs via the cationic manifold and the alkene is isomerized by a hy-dropalladation/dehydropalladation reaction. The minor product 2,5-dihydrofuran 73 is obtained in 26% yield with modest enantioselectivity favoring the opposite absolute configuration at the key center. Critical to the reaction is the use of the sterically demanding and highly basic proton sponge [l,8-bis(dimethylamino)naphthalene] as the base. It is... 

For alkenyl and aryl halides, a neutral mechanistic manifold has been invoked in which one arm of the phosphine ligand must dissociate (13- 17) to create a vacant site on palladium for alkene coordination (17- 18) [6,11]. The lower enantioselectivities observed for Mizoroki-Heck reactions occurring via the neutral pathway have been attributed to this ligand dissociation. To achieve higher enantioselectivities, the reaction of alkenyl and aryl halides may be directed into the cationic manifold by the addition of the silver or thallium... 

Presumably the reaction occurs via the cationic manifold of the Mizoroki-Heck reaction and a bidentate phosphine is employed. Subsffate alkene geometry is critical to the stereochemical outcome and enantioselectivity of the reaction. The (Z)-alkenyl triflate 77 cyclizes to the enantiomeric enol ether 78 in high yield and greater enantioselectivity. The reaction can be utilized to perform a kinetic resolution, although reports are rare. Shibasaki... 

Enantioselective intramolecular cascade Mizoroki-Heck reactions have been shown to proceed with moderate to good selectivity via the cationic manifold. There are surprisingly few enantioselective examples, given the wide array of transformations known for cr-alkylpalladium intermediates in racemic or diastereoselective reactions. All of the nongroup-selective, enantioselective, cascade, intramolecular Mizoroki-Heck reactions reported to date involve formation of one quaternary centre. A substantial advance would be to expand the range of transformations available for the a-alkylpalladium species and... 

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