Norbomene carbopalladation

Although the belief that steric factors influence norbomene extrusion is reasonable and supported by Catellani s studies, it is entirely possible that norbomene carbopalladation and extrusion are reversible processes. If so, a species related to 4 may be trapped as the mono-o/t/to-alkylated product. Although mono-functionalization has been observed in stoichiometric studies by Catellani [31, 42], catalytic reactions generally do not afford monoalkylated products. Interestingly, Lautens has shown that in some particular systems mono-alkylation is possible, which may occur as a result of a sterically congested system (Scheme 14) [44], This does lend some evidence to the possibility that norbomene carbopalladation and extrusion are reversible steps, and may occur between ortho functionalization steps. 

Under the reaction conditions, phenylacetylene was found to be a much more reactive coupling partner than arylboronic acids in the analogous Suzuki-Miyaura coupling, as in addition to the desired product (38), alkynylation and further addition reactions occurred with a variety of transient palladium(II) species (Scheme 27). Despite these undesired side reactions, Catellani was able to fine-tune the reaction conditions to form predominantly product 38 or 39. The formation of the desired product 38 (and suppression of product 39) is promoted by acceleration of norbomene carbopalladation by KOAc [47] and by using an excess of alkyl halide affording several structurally similar unsymmetrical alkyne products in good yields (Scheme 28). 

While the PNP dimer was an efficient catalyst for the ort/toalkylation/ Mizoroki-Heck reaction, the practicality of the transformation is lessened by the fact that the PNP dimer is not commercially available, and can be quite difficult to prepare. Thus, Catellani adapted the reaction conditions to include commercially available and air-stable Pd(OAc)2 as the catalyst source [46], Under these conditions, the ortho-u kylation/Mizoroki-I Ieck coupling of aryl iodides containing a pre-existing ortho substituent could be carried out. The reaction required higher temperatures, and the addition of KOAc to promote the carbopalladation of norbomene [47] and encourage the o/t/zo-alkylation pathway vs a direct Mizoroki-Heck coupling. 

This unusual strategy is thought to make use of the different reactivities of palladium(O), palladium(II) and palladium(IV) intermediates. Mechanistically, the reaction is proposed to occur via initial oxidative addition of palladium(O) to the aryl iodide, followed by carbopalladation with norbomene to afford alkyl palladium species II (Scheme 18). 

The transient involvement of norbomene in Heck reaction via its carbopalladation and help to functionabzation of the ortho position(s) is highly profitable. Its further exploitation includes oalkylation at the site of Heck reaction and amination. ... 

A somewhat different example of /6-carbon elimination was observed by Catel-lani and Chiusoli in 1983 [14]. Reaction of two molecules of norbomene (79) with bromobenzene gave rise to 83. Stepwise carbopalladations of norbomene generate 80 and 81. Then /6-carbon elimination yields the alkylpalladium 82 and /6-H elimination affords 83. As described in Chapter 3.8.1, the deinsertion of norbomene from 84 to generate norbomene (79) and arylpalladium 85 is an example of /6-carbon elimination. 

Although the results shown in Schemes 15-17 amply demonstrate the predominance of the flntl-addition in heteropaUadation, various factors can readily render the syn-heteropalladation reactions more favorable than the corresponding anh-addition processes. Such i yn-addition processes may well be concerted as in the cases of hy-dropalladation and carbopalladation. As a representative example, norbomene has been converted to iyn-7-norbomenol,f which can readily be explained in terms of syn-oxypalladation-rearrangement-elimination, as shown in Scheme 18. 

When the /3-hydride elimination in the intermediate is retarded or even impossible, as in the carbopalladation products of alkynes or norbomene, the respective cyclopentan-nelation products are formed in higher yields (Scheme 5),[i9].[20]... 

When the carbopalladated relay is less prone to undergo /S-hydride elimination (as, e.g., a corbopalladated methylenecyclopropane moiety) or the /S-hydride elimination is even completely blocked [as, e.g., an alkyne, norbomene (Scheme 2) ", or acenaphthylene (Scheme 3)] and the respective cyclopentannelation products can be isolated in... 

Since strained alkenes and cycloalkenes are particularly good ligands for palladium, even an ort/io-allenyl-substituted arylpalladium iodide will first carbopalladate a norbomene intermolecularly before the allenyl unit intercepts the relay norbomylpalladium species... 

Norbomene can serve as an excellent external relay, for example, for the alkenylpalla-dium species first formed by intramolecular carbopalladation of an ort/to-alkynyl-substituted arylpalladium halide. The 2-alkenylnorbonylpalladium halide formed by intermolecular carbopalladation then undergoes another intramolecular carbopalladation, this one in a 3-exo-trig mode, and subsequent /3-hydride elimination terminates the cascade process to yield a cyclopropanated norbomene derivative (Scheme... 

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). ... 

Disubstituted alkenes and other alkenes that can undergo living carbopalladation (e.g., norbomene) can participate in the carbopalladation-carbonylative termination... 

As in the cases of termination by lactonization and lactamization, some specially structured alkenes, such as norbomene and related alkenes, can participate in intermolecular carbopalladation-carbonylative ketonization tandem processes. In the reactions shown in Scheme 22, the acylpalladium intermediates undergo intramolecular acylpalladation with arenes to provide ketones. ... 

In this novel domino sequence, norbornene (or norbomadiene) acts as a promoter as well as a reaction partner. It enters and exits the catalytic cycle and is eventually incorporated in the product, and therefore the reaction requires an excess of this reagent. The standard Pd-catalyzed/norbomene-mediated ortho alkylation of the aryl iodide with the alkyne would form the arylpalladium species 146 (Scheme 3.36). Intramolecular carbopalladation onto the tethered alkyne unit gives vinylpalladiuml47. Intermolecularcarbopalladationwitha moleculeofnorbornene... 

If however, a bicyclic aUsene is used, 5yn-/S-hydride elimination from the carbopalladation product is disfavored. and the reaction proceeds further through a sequence of steps until a favorable reductive elimination becomes feasible. A precedent of an insertion equi-hbrium not leading to /S-hydride elimination can be found in nickel chemistry, where it was shown that norbomene inserted into a methaUylnickel bond in the presence of acetate anion and deinserted in the presence of hydrogen halides (Scheme 4). 

---