Intermolecular reactions intramolecular nucleophilic trapping

Both reaction modes A and B have been observed for carbopalladations of methylenecyclopropane derivatives 59a,b with subsequent intramolecular nucleophilic trapping of the intermediate allylpallatium species in or IV, respectively, depending on the tether lengths between the methylenecyclopropane and the dimethyl malonate moieties. The same carbopalladations of unsubstituted methylenecyclopropane 43 (=60a) and pentyli-dene-cyclopropane (60b) with subsequent intermolecular trapping by carbon nucleophiles were found to generally proceed by mode B via intermediates II, V, IV to yield ringopening products 61 and 62, respectively (Scheme 16). 

As outlined in Sect. B and C, catalytic intermolecular carbopalladations of allenes followed by either /3-hydride elimination or intermolecular nucleophilic trapping provide 1,3-dienes or allyl derivatives bearing the nucleophile moiety, respectively, while an intermolecular carbopalladation followed by intramolecular trapping sequential reaction provides cyclic skeletons (Scheme 27). In Type I, the nucleophilic moiety is connected with the C—X bond, and in lype II it is attached to the allene moiety. 

The proposed catalytic cycle of the ruthenium-catalyzed intermolecular Alder-ene reaction is shown in Scheme 21 (cycle A) and proceeds via ruthenacyclopentane 100. Support for this mechanism is derived from the observation that the intermediate can be trapped intramolecularly by an alcohol or amine nucleophile to form the corresponding five-or six-membered heterocycle (Scheme 21, cycle B and Equation (66)).74,75 Four- and seven-membered rings cannot be formed via this methodology, presumably because the competing /3-hydride elimination is faster than interception of the transition state for these substrates, 101 and 102, only the formal Alder-ene product is observed (Equations (67) and (68)). 

Toward the synthesis of heterocycles utilizing isocyanide, this concept was expanded to the intramolecular trapping of the nitrilium intermediate in the Ugi-type reaction. When a molecule contains both an electrophile (C=N) and a potential nucleophilic group (Nu ), intramolecular trapping of the nitrilium intermediate could be readily realized relative to the intermolecular version (Scheme 11.8). Based on this hypothesis, we chose A -acyl azomethine imine as an isocyano-phile, which is an extended conjugated 1,3-dipole and could function as a 1,5-dipole to afford the corresponding heterocycles (Figure 11.7). 

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