Carbopalladation carbon nucleophiles

Facile reaction of a carbon nucleophile with an olefinic bond of COD is the first example of carbon-carbon bond formation by means of Pd. COD forms a stable complex with PdCl2. When this complex 192 is treated with malonate or acetoacetate in ether under heterogeneous conditions at room temperature in the presence of Na2C03, a facile carbopalladation takes place to give the new complex 193, formed by the introduction of malonate to COD. The complex has TT-olefin and cr-Pd bonds. By the treatment of the new complex 193 with a base, the malonate carbanion attacks the cr-Pd—C bond, affording the bicy-clo[6.1,0]-nonane 194. The complex also reacts with another molecule of malonate which attacks the rr-olefin bond to give the bicyclo[3.3.0]octane 195 by a transannulation reaction[l2.191]. The formation of 194 involves the novel cyclopropanation reaction of alkenes by nucleophilic attack of two carbanions. 

Various nucleophiles can attack coordinated alkenes. Typically the attack of OH anion on ethylene coordinated to Pd(II) as shown by 71 takes place in the Wacker process to afford acetaldehyde (72) [4], Also COD (73), coordinated to PdCl2, was shown to be attacked by carbon nucleophiles such as malonate to give 74. This reaction is the first example of carbopalladation of alkenes [5],... 

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]. 

Nucleophilic trapping agents used in the Type II Ac-Pd process are not limited to MeOH and other alcohols. A wide range of heteroatom and carbon nucleophiles may be used as in the cases of the Type II cyclic carbopalladation processes terminated by various nucleophilic reagents (Sect. 2.1.2). A couple of reactions shown in Scheme 58 [ 145] provide additional examples of heterocycles synthesis via Type II Ac-Pd process terminated by cross-coupling. 

Of the two reaction types involving -carbon elimination, the former through CPC-Pd is relatively more common. For instance, in the Heck-type reaction of vinyl bromides with MCP (Eq. 1), carbopalladation on the exo-methylene moiety takes place to give a CPC-Pd intermediate. Then, p-carbon elimination, hydrogen migration, and reaction with a carbon nucleophile successively occur to give rise to three-component coupling products [13]. 

Intramolecular carbopalladation of the unsaturated jS-diketone 126 catalyzed by the combination of PdCl2 with CuCb at room temperature provided the cyclo-hexenone 127 in very high yield (97 %). In other words, facile oxidative alkylation of an unactivated alkene with a carbon nucleophile took place [54],... 

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). 

IV.3.2 CASCADE CARBOPALLADATION TERMINATED BY NUCLEOPHILES 1407 B.ii. Termination by Carbon Nucleophiles... 

Carbopalladation Reactions. The transition metal-induced addition of carbon nucleophiles to unactivated alkenes is an attractive area of research. Although the addition of stabilized carbon nucleophiles or an alkoxycarbonyl group across the C=C bond of an unactivated olefin was initially achieved in the presence of stoichiometric amount of Pd salts, such as Pd(OAc)2 or PdCl2(CH3CN)2, more recently this reaction has been achieved catalytically. 

Reaction with Carbon Nucleophiles. The cyclooctadiene (cod) complex of PdCl2, which is insoluble in organic solvents, reacts in ether with malonate or acetoacetate under mild heterogeneous conditions facile carbon-carbon bond formation takes place to give a new complex in a quantitative yield. Further intramolecular reaction of the cort5)lex with a base affords the cyclopropane derivative. Attack of a second malonate on the complex yields the [3.3.0] system (eq 16). Carbopalladation of the double bond of Al-vinylcarbamate with acetoacetate at —78 °C, and subsequent carbonylation of the Pd-carbon bond, proceeds smoothly to yield the carhocarbonylation product in 92% yield (eq 17). ... 

Negishi and co-workers demonstrated the feasibility of this carbopalladation mode on an allene in an intramolecular approach to medium and large rings [80]. The new C —C bond is fornied at the central carbon atom of the allene moiety to give a jr-allylpalladium complex, which in turn can be trapped by a variety of nucleophiles (arylstannanes to give arylated products, malonates, phenols, amines, etc.) (Scheme 3-27). The yields are remarkably good without using sophisticated nucleophile delivery techniques. 

Interestingly, this 1,4-carbochlorination occurs syn, which constrasts with that via the vinylpalladation in Eq.(49), which occurs anti. An explanation for this difference is that the allylsilane attacks the palladium-diene complex anti, leading to a rrans-carbopalladation of the double bond. This is the first example of nucleophilic attack by an allylsilane on an olefin coordinated to a metal. Direct evidence for a frans-carbopalladation was provided by the isolation of the proposed 7r-allyl intermediate of Eq.(51) as its chlorodimer 98a from reaction of 97 with Li2PdCl4 in the absence of benzoquinone [Eq.(52)] [119b]. The trans relationship between palladium and the carbon that has attacked the diene was established by the reporter ligand technique used for 41 in Section 8.3.1.1 under Intramolecular 1,4-diacyloxylation . 

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