Intermolecular Nucleophilic Trapping

Nucleophiles. Trapping of acylpaUadium species formed via cycUc acylpaUadation with external heteroatom nucleophiles has been achieved almost exclusively by using alcohols, such as MeOH, EtOH, i-PrOH, and t-BuOH. Their nucleophUicity is such that the above-mentioned requirement for the relative rates among three competing processes, that is, intramolecular Ac-Pd > nucleophilic trapping > intermolecular Ac-Pd, can often be satisfied at least in cases where five- and six-membered ketones are desired. 

Carbonyl compounds can also act as the nucleophiles in intermolecular processes with 1,6-enynes. Thus, the gold (I)-catalyzed reaction between enynes and aldehydes or acetone gives stereoselectively tricyclic compounds (equation 71). The transformation is mechanistically intriguing, as it proceeds by a rearrangement of the initially formed cyclopropyl gold carbene (the intermediate in the double-cleavage mechanism), which is then trapped by the carbonyl compound to form the products. 

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). 

C. INTERMOLECULAR CARBOPALLADATION OF ALLENES FOLLOWED BY INTERMOLECULAR NUCLEOPHILIC TRAPPING... 

In these cases the interactions between and play the major role to determine the stereochemical outcome of the sequence of an intermolecular carbopalladation and an in-termolecular nucleophilic trapping. Some typical results are listed in Scheme 12. In the case of 29, the methyl group at the 2-position of the alkenyl bromide clearly shifts the equilibrium between anti-26 and syn-16 exclusively to anti-26 (Scheme 2)P ... 

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. 

Very recently, Petersen and Nielsen [44] could not only show that the nucle-ophihc trapping of the acyliminium ion can be conducted in an intramolecular manner but also extend the sequentially Ru-catalyzed RCM-isomerization sequence to exploit the heteroaromatic hydroxyl tautomer for an aldol condensation to give pyrrolone derivatives 22 (Scheme 12.14). The combination of RCM-isomerization-intermolecular nucleophilic trapping and the acid-catalyzed aldol condensation has been elegantly illustrated in the total synthesis of the antileukemic indole alkaloid violacein. 

In 1995 Grigg and co-workers reported a similar cascade consisting of an intramolecular carbopalladation and intermolecular nucleophilic trapping (Scheme 44). The regioselectivity of the aUylic nucleophilic substitution can be controlled completely by using different bases. 

The reactive nature of carbocationic THP intermediates in Prins cyclizations is not limited to intermolecular nucleophilic trapping. The cyclic carbocation 133... 

Generation of Electrophilic Cations. Complexation of Et2AlCl to ketones and aldehydes activates the carbonyl group toward addition of a nucleophilic alkyl- or allylstannane or allylsilane. Et2AlCl has been used to initiate Beckmann rearrangements of oxime mesylates. The ring-expanded cation can be trapped intermolecularly by enol ethers and cyanide and in-tramolecularly by alkenes (eq 5). ... 

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