Organopalladium intramolecular reaction

The numerous palladium-catalyzed organic reactions have a relatively small number of elementary steps. Oxidative Addition, Reductive Elimination, ligand coordination, and addition to coordinated ligands (either intramolecular or intermolecu-lar) are the most important classes of transformations in most palladium catalytic cycles. The exact nature of the species within the coordination sphere of palladium and the order in which the steps take place are responsible for the variety of the organic products produced. Four representative and important palladium-catalyzed reactions are briefly discussed here to illustrate the range of organopalladium reactions. 

Palladium-catalyzed coupling reactions of the Heck type have in many instances involved indole and pyrrole derivatives. Although the mechanisms are complex, organopalladium species are implicated (84H(22)1493). Vinylation of A-substituted-3 -iodoindoles with amidoacrylate groups provides a useful functionalization of indoles (Scheme 81) (90JOM(39l)C23). Yields are improved in intramolecular reactions, e.g. (406 — 407) and (408 — 409) <92H(34)219,91CPB2830). 

Carbopalladation occurs with soft carbon nucleophiles. The PdCl2 complex of COD (100) is difficult to dissolve in organic solvents. However, when a heterogeneous mixture of the complex, malonate and Na2C03 in ether is stirred at room temperature, the new complex 101 is formed. This reaction is the first example of C—C bond formation and carbopalladation in the history of organopalladium chemistry. The double bond becomes electron deficient by the coordination of Pd(II), and attack of the carbon nucleophile becomes possible. The Pd-carbon n-bond in complex 101 is stabilized by coordination of the remaining alkene. The carbanion is generated by treatment of 101 with a base, and the cyclopropane 102 is formed by intramolecular nucleophilic attack. Overall, the cyclopropanation occurs by attack of the carbanion twice on the alkenic bond activated by Pd(II). The bicyclo[3.3.0]octane 103 was obtained by intermolecular attack of malonate on the complex 101 [11]. 

Organopalladium complexes do usually not transfer a formal carbanion to aldehydes or ketones, but intramolecular Barbier-type reactions of this kind have been observed (Scheme8.2). 

Coperet C, Negishi E (2002) Intramolecular Acylpalladation Intramolecular Acylpalladation Reactions with Alkenes, Alkynes, and Related Unsaturated Compounds. In Negishi E, de Meijere A (eds) Handbook of Organopalladium Chemistry for Organic Synthesis. Wiley, New York, p 2519... 

A much wider range of organopalladium compounds is available, however, by means of cyclopalladation reactions. Such reactions involve a Pd(II) salt and an N or P ligand capable of undergoing intramolecular C—H bond oxidative addition. HCl is eliminated as a by-product, and the reactions occur most readily when a five-membered chelate ring is formed " ... 

For intramolecular Heck reactions, Ihe migratory insertion of the initial organopalladium... 

Several other examples of stereoselective synthesis of polycyclic ketones, via carbonylative [2 + 2 + 1] cycloaddition of organopalladium compounds derived from norbornene and norbor-nadiene, have been reported53,54,121. These reactions are useful in the synthesis of cyclopen-tanoid compounds, such as dihydrojasmone54 The nickel-catalyzed version of this method was used in a total synthesis of methylenomycin B55 and in the stereoselective synthesis of bicy-clo[3.3.0]oct-l-en-3-one derivatives56. Thus, (E)- or (Z)-9-bromo-l-methoxy-7-nonen-2-yne (5), upon intramolecular carbonylative cyclization promoted by tetracarbonyl nickel, afford the same stereoisomer of methyl 1,2,4,5.6,6a-hexahydro-3-methoxymethyl-2-oxo-l-pentaleneac-etate (6) in 43-50% yield with a relative trans configuration of the H-l and H-6a protons. 

In all of the reactions discussed above, the carbopalladation of the allene occurred regioselectively in such a way that the substituent of the first formed organopalladium intermediate would be attached to the central carbon atom of the allene moiety to form a tt-allylpalladium intermediate. However, Grigg et al. and later Oppolzer et al. observed that the intramolecular carbopalladation of the first formed allene 165 proceeded in a completely different manner (Scheme 53). Instead of the formation of a tt-allylpalladium conplex, a reverse regioselectivity to form a Csp2—Pd intermediate was observed. 

The carbopalladation is a central reaction in organopalladium chemistry and is extensively presented in Part IV. hi most reactions, a discrete organopalladium intermediate adds to a donble or triple bond. In this section, the reaction of an alkyl iodide with di-ethylzinc in the presence of a palladium(O) catalyst is presented. Such reaction conditions generate an alkyl radical that readily adds intramolecularly to a double bond, leading to an organozinc derivative (Scheme 1). The combination of a radical cyclization with the formation of an organometallic product allows new synthetic applications that will be discnssed. Closely related Ni-catalyzed cyclizations will also be briefly presented. 

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