Carbopalladation carbon-palladium formation

A.i. Formation of rr-Allylpalladium Species via Stoichiometric Reactions of Carbon-Palladium Species with AUenes Regiochemistry of Carbopalladations of Allenes... 

Recently, Wang et al. reported anovel palladium-catalyzed sequential Sonogashira/ carbopalladative cyclization/Suzuki reactions involving multiple carbon-carbon bond formation using protected homopropargyl alcohol 155 under mild conditions [59] (Scheme 6.40). Various indene derivatives 156 could be constructed efficiently with good yields in this transformation. Moreover, this reaction has a wide tolerance of various substituents in the substrates. 

On the other hand, the terminally unsubstituted bromoenediyne 238 undergoes 5-exo-trig cyclization, instead of 6-endo-trig, of 239 to generate the neopentyl-palladium 240, and subsequent 3-exo-trig carbopalladation gives the cyclopropane 241, which is stabilized by the formation of jr-allylpalladium 242. Then y3-carbon elimination of 241 afforded the homoallylpalladium 243, and y3-H elimination yields the fulvene 244 [66]. 

As another possibility, the reaction of 44 might be explained by the formation of palladium alkoxide 49, followed by jS-carbon elimination to afford 50. Carbopalladation (5-exo cyclization) of 50 gives 51, and reductive elimination produces 45 via 48. However, this route seems to be less likely, since more substituted carbon migrates in this type of reactions as demonstrated by the following examples [9]. 

In this section, Pd(0)-catalyzed reactions of allenes with nucleophiles are treated, which are clearly different mechanistically from the reactions explained in the above. Attack of nucleophiles may occur at C-1, C-2, and C-3 carbons of the allenes 63. Among them, attack at C-3 to give 64 is predominant. Most importantly, reactions of allenes with pronucleophiles start by the oxidative addition of pronucleophiles to Pd(0) to generate H-Pd-Nu 65. The formation of 64 by hydro-carbonation can be explained in two ways in the case where Nu-H is the carbon pronucleophile. As one possibility, hydropalladation of one of the two double bonds occurs to afford the terminal palladium intermediate 66, which is stabilized by the formation of 7r-allyl complex 67, and reductive elimination provides the C-3 adduct 68. Another possibility is carbopalladation to generate 69, and subsequent reductive elimination provides 68. Of these two possibilities, the hydropalladation mechanism is preferable. 

Cascade reactions arising from sequential carbopalladations are especially valuable for the construction of various carbo- and heterooligocyclic systans with three, four, or even more annelated rings. The Heck reaction has successfully been employed in various inter-inter-, intra-inter-, as well as all-intramolecular reaction cascades (Sect. IV.3). In the carbopalladation step of the Heck reaction (Scheme 6) a new metal-carbon bond is formed, which, in principle, can undergo any of the typical reactions of a hydride elimination is not too fast. When the /S-hydride elimination is totally suppressed, the palladium species can undergo a number of reactions with the formation... 

The observed general predominance of cis addition products following the carbopalladation step (Schemes la and 2) and the formation of cyclic derivatives (Scheme lb) appear to argue in favor of a mechanism involving a syn addition of the organic residue and the palladium moiety to the carbon-carbon triple bond. The appearance of final products as trans derivatives is more likely to indicate the intermediacy of cis -adducts capable of isomerization to the tran -adducts (Scheme 3) rather than the existence of a direct trans addition paralleling the cis addition pathway. 

Examples of this trend are numerons. For instance, steric effects appear to be responsible for the remarkable legioselectivity observed in the Pd-catalyzed hydroalkeny-lation of 4-phenylcyclohex-l-enyl triflate with l-(p-acetamidophenyl)-3,3-dimethyl-l-propyne in the presence of potassium formate (Scheme 5). In this reaction, which is also highly stereoselective, the added alkenyl group is placed regioselectively on the less stoically encumbered end of the carbon-carbon triple bond and the hydrogen (the palladium moiety in the carbopalladation adduct) on the more stericaUy congested end. 

Mono- or di-arylaied products may be formed by a-arylation of -dicarbonyl compounds, such as malonamide esters, with arynes generated by reaction of fluoride with ortho-silylaryltriflates. A similar method of benzyne generation has been used in the a-arylation of -ketoamides in a procedure which may be modified to yield asymmettic products. The reaction of 2-haloacetanilides with arynes in the presence of a palladium catalyst may produceiV-acylcarbazoles such as (26). Possible pathways are initial formation of a palladacycle with aryne followed by oxidative addition of the haloacetanilide, or direct insertion of the palladium into the carbon-halogen bond of the acetanilide followed by carbopalladation of the aryne. ... 

---