Jr-allylpalladium complex

A mechanistic rationale for the Pd-catalyzed addition of a C-H bond at nitriles to allenes is outlined in Scheme 3. The oxidative insertion of Pd(0) into the C-H bond of nitrile 1 produces the Pd(II) hydride species 16 (or alternatively a tautomeric structure E E2C=C=N PdH Ln may be more suitable, where E = H, alkyl, aryl and/or EWG). Carbopalladation of the allene 2 would afford the alkenylpalladium complex 17 (carbopalladation mechanism), which would undergo reductive coupling to give the addition product 3 and regenerates Pd(0) species. As an alternative mechanism, it may be considered that the hydropalladation of allenes with the Pd(II) intermediate 16 gives the jr-allylpalladium complex 18 which undergoes reductive coupling to afford the adduct 3 and a Pd(0) species (hydropalladation mechanism). 

It is very well known that jr-allyl palladium complex 1, which is a key intermediate for the Tsuji-Trost type allylation, has an electrophilic character and reacts with nucleophiles to afford the corresponding allylation products. We discovered that bis 7r-allyl palladium complex 2 is nucleophilic and reacts with electophiles such as aldehydes [27] and imines [28-32] (Scheme 2, Structure 2). We have also shown that bis 7r-allyl palladium complex 2 can act as an amphiphilic catalytic allylating agent it reacts with both nucleophilic and electrophilic carbons at once to produce double allylation products [33]. These complexes incorporate two allyl moieties that can bind with different hapticity to palladium (Scheme 3). The different complexes may interconvert by ligand coordination. The complexes 2a, 2b and 2c are called as r]3,r]3-bisallypalladium complex (also called bis-jr-allylpalladium complex), r)l,r)3-bis(allyl)palladium complex, -bis(allyl)palladium complex, respectively. Bis zr-allyl palladium complex 2 can easily be generated by reaction of mono-allylpalladium complex 1 and allylmetal species 3 (Scheme 4) [33-36]. Because of the unique catalytic activities of the bis zr-allyl palladium complex 2, a number of interesting cascade reactions appeared in the literature. The subject of the present chapter is to review some recent synthetic and mechanistic aspects of the interesting palladium catalyzed cascade reactions which in-... 

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. 

The reactions of type III proceed by attack of nucleophile at the central sp carbon of the allenyl system of the allenyl complex 8. Reactions of soft carbon nucleophiles, derived from active methylene compounds such as )3-keto esters or malonates, and oxygen nucleophiles belong to this type. The attack of the nucleophile generates the intermediate 12, which is regarded as a palladium-carbene complex 13. The intermediate 12 picks up a proton from the active methylene compound and the jr-allylpalladium complex 14 is formed, which undergoes further reaction with a nucleophile as expected hence two nucleophiles are introduced to give the alkenes 15 (Scheme 11-5). 

In the absence of a nucleophile, jr-allylpalladium complexes bearing alkyl sub-stituent(s) at the allylic carbon(s) undergo P-hydrogen elimination to give dienes (eq (113)) [144]. 

Scheme 3-54). This transformation constitutes a cascade of an intramolecular Heck insertion and subsequent heterocyclization. The initially formed arylpalladium species attacks the bridgehead position of the diene functionality in 238 to form a jr-allylpalladium complex which is trapped by the internal nucleophilic phenol moiety (cf. Scheme 3-26). Since the starting diene 238 can be prepared in both enantiomeric forms by asymmetric reduction of a ketone, this sequence allows the preparation of both the natural morphine and its unnatural enantiomer. 

Japanese chemists have reported a stereoselective synthesis of humulene (9), an 11-membered cyclic sesquiterpene, by intramolecular a-alkylation of a keto group by a jr-allylpalladium complex. The starting material (7) was derived from geranyl acetate. In this case, the efficiency of the cyclization was markedly improved by addition of a diphosphine ligand such as l,3-bis(diphenylphosphino)-... 

In addition, jr-allylpalladium complexes 1 and 2 are formed as intermediates in the reactions of organic halides with 1,3- and 1,2-dienes. Usually these tt-allylpalladium complexes, without isolation, undergo a variety of transformations as summarized in Scheme 4.1, offering many useful synthetic methods. 

Formation of 1 1 adducts from substituted dienes 49 can be understood by the following mechanism, hi this case, generation of bis-7r-allylie palladium is not possible for steric reasons. Instead, insertion of a diene to H-Pd bond of H-Pd-Nu occurs to afford the jr-allylpalladium complex 50, and nucleophilic attack at the allylic terminus gives 51. 

The intermolecular diamination of 1,3-dienes with acyclic ureas to provide monocyclic or bicydic urea derivatives has been achieved by Uoyd-Jones and Booker-Milburn through use of a palladium catalyst combined with either benzo-quinone or O2 as an oxidant [65]. For example, diene 81 was converted to urea 82 in 82% yield (Eq. (1.37)). These transformations are mechanistically distinct from the reactions described above, and appear to involve intermediate jr-allylpalladium complexes. 

B.vi.b. Coupling of Building Block to Solid Support Via jr-Allylpalladium Complexes. The reactions of immobilized nucleophiles with 7r-allylpalladium precursors have been described for various combinations.f A double allylation reaction has been shown using an immobilized nitrogen nucleophile with 2-hydroxymethylallyl methyl carbonate. After the first allylic substitution, acylation and a subsequent coupling with various nucleophiles provided access to substituted glycine derivatives (Scheme 22). ... 

Palladium-catalyzed allylic substitution may be regarded as a special case of cross-coupling with jr-allylpalladium complexes. First developed as a stoichiometric technique, this reaction was later realized in a catalytic mode, and became a valuable tool of organic synthesis, as it allows for a broad variation of both allylic substrates and nucleophiles. 

The use of chiral ligands on the jr-allylpalladium complexes leads to induction of chirality with however rather low optical yields [37]. 

While reaction of a steroidal jr-allylpalladium complex with AcOK yields the allyl acetate arising from trans attack, treatment of a steroidal aikene with PdCl2/CuCl2/AcOK/AcOH gave the allyl acetate arising from cis attack. ... 

Based on this reaction, allylic alkylation of alkenes is possible. Active methylene compounds, such as malonates and /8-keto esters, can be introduced to a steroid skeleton by the reaction of the steroidal jr-allylpalladium complex in DMSO (eq 20). 4 Jijg reaction of carbon nucleophiles also proceeds in the presence of an excess of triphenylphosphine (eq 21). ... 

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