Alkyne derivatives carbopalladation

To probe the reaction mechanism of the silane-mediated reaction, EtjSiD was substituted for PMHS in the cyclization of 1,6-enyne 34a.5 The mono-deuterated reductive cyclization product 34b was obtained as a single diastereomer. This result is consistent with entry of palladium into the catalytic cycle as the hydride derived from its reaction with acetic acid. Alkyne hydrometallation provides intermediate A-7, which upon cw-carbopalladation gives rise to cyclic intermediate B-6. Delivery of deuterium to the palladium center provides C-2, which upon reductive elimination provides the mono-deuterated product 34b, along with palladium(O) to close the catalytic cycle. The relative stereochemistry of 34b was not determined but was inferred on the basis of the aforementioned mechanism (Scheme 24). 

The alkyne relay, in particular, has frequently been used for cascade carbopaliadations with ring formation, because a carbon-carbon triple bond is more reactive toward carbopalladation than a carbon-carbon double bond. Thus, methyl -iodocinnamate 70 reacts with diphenylacetylene 71 to yield the methylenediphenylindene derivative 72 (Scheme 22). ... 

The cyclic carbopalladation-cross-coupling tandem reaction has been extensively developed over the past several years. Despite earlier favorable findings with A1 and Zr [84], these metals are still scarcely used. On the other hand, organometals containing Sn and B have been widely used, and favorable results have been obtained for the formation of ffve-membered car-bocycles and heterocycles containing N and O from halodienes [88] (Eqs. 1 and 2 in Scheme 29), haloenynes [89-92] (Eqs. 3-5 in Scheme 29), haloaryl-alkynes [94,95] (Eqs. 6 and 7 in Scheme 29), and allenene derivatives [93,96] (Eqs. 8 and 9 in Scheme 29). 

Selective synthesis of benzene derivatives via partially intramolecular cyclic carbopalladation is considerably more complex than the corresponding all-intramolecular processes. As it is generally difficult to specify the cascade-initiation point in the Type Ha cyclization process, it would generally be the least selective path. A priori, the most favorable might be the intra-inter cascade cyclization process (Type lib), since both the point of initiation and the queuing order between the two alkynes is sharply differentiated by the fact that one is intramolecular, while the other is intermolecular. Still, in-... 

Many other related but alternative routes to benzene derivatives are conceivable. One inter-intra cascade carbopalladation route which is potentially highly selective is shown in Eq. 1 of Scheme 46 [11]. Another proceeds via cyclic allenylpalladation of alkynes followed by cross-coupling with PhB(OH)2 [127] (Eq. 2 of Scheme 46). Yet another related process is the synthesis of naphthalene derivatives shown in Eq. 3 of Scheme 46 [128]. If the regioselectivity problem could be overcome, it would provide an attractive route to naphthalenes. 

The inter-intermolecular carbopalladation cascade, starting with the palladium intermediate from /3-halostyrene derivatives and two molecules of an alkyne, does not yield a benzene, but highly substituted fulvene derivatives, albeit in moderate yields only (Scheme 47, Eqs. 1 and Fulvene derivatives are also formed from 1-haloalkenes and 1,6-diynes (Schemed , Eq. 3). ... 

An analogous reaction mode is followed in the 1 2 cross-coupling of 2-bromostyrene with acenaphthylene, which yields a bisannelated tetrahydrofulvene (Scheme 48)J Norbomene can favorably serve as a relay for cascade carbopalladations as the /S-hydride elimination is virtually impossible. The reaction always starts with an alkenyl-or arylpaUadium starter, generated either by oxidative addition of an alkenyl or aryl halide to a paUadium(O) species or by hydro- or carbopalladation of an alkyne, adding to the double bond. With /3-bromostyrene, norbomene can yield the same type of bisannelated tetrahydrofulvene derivative " as with acenaphthylene, but under different reaction conditions can also react with a 2 1 stoichiometry to give a cyclohexadiene-annelated norbomane derivative (Scheme 49). ... 

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