Palladium -catalyzed reactions intramolecular

In the second approach55 an allylsilane was employed as carbon nucleophile in the side chain. Allylsilanes have been frequently used as masked allyl carbanions, usually in reactions with a keto function57. Palladium-catalyzed reaction of allylsilane 57 with LiCl under similar conditions as used for the other intramolecular 1,4-oxidations afforded 58 (equation 22). Interestingly, the carbochlorination over the diene was highly 1,4-syn... 

Intramolecular arylation of G-H bonds gives cyclic aromatic compounds. In this intramolecular arylation, the carbon-palladium cr-bond is first formed by the oxidative addition of Pd(0) species and then the resulting electrophilic Pd(n) species undergoes the intramolecular G-H bond activation leading to the formation of the palladacycle, which finally affords the cyclic aromatic compounds via reductive elimination.87 For example, the fluoroanthene derivative is formed by the palladium-catalyzed reaction of the binaphthyl triflate, as shown in Scheme 8.88 This type of intramolecular arylation is applied to the construction of five- and six-membered carbocyclic and heterocyclic systems.89 89 89 ... 

Most of the work on the C-N bond-forming crosscoupling reactions has concentrated on the formation of aromatic C-N bonds. Recent studies show that the application of cross-coupling reactions to alkenyl halides or triflates furnished enamines (Scheme 19) (for palladium-catalyzed reaction, see 28,28a-28d, and for copper-catalyzed reaction, see 28e-28g). Brookhart et al. studied the palladium-catalyzed amination of 2-triflatotropone 109 for the synthesis of 2-anilinotropone 110.28 It was found that the reaction of 109 proceeded effectively in the presence of racemic BINAP and a base. As a simple method for the synthesis of enamines, the palladium-catalyzed reactions of alkenyl bromide 111 with secondary amine were achieved under similar conditions.2841 The water-sensitive enamine 112 was isolated as pure compound after dilution with hexane and filtration through Celite. The intramolecular cyclization of /3-lactam 113, having a vinyl bromide moiety, was investigated by Mori s... 

The silyl group in 311, prepared by intramolecular silylformylation, is intermolecularly substituted by a phenyl group by a palladium-catalyzed reaction with Phi to give coupled product 312 (Equation (56)). ... 

The Cope rearrangement of 24 gives 2,6,10-undecatrienyldimethylamine[28], Sativene (25j[29] and diquinane (26) have been synthesized by applying three different palladium-catalyzed reactions [oxidative cyclization of the 1,5-diene with Pd(OAc)2, intramolecular allylation of a /i-keto ester with allylic carbonate, and oxidation of terminal alkene to methyl ketone] using allyloctadienyl-dimethylamine (24) as a building block[30]. 

As for the biaryl ether containing macrocycles, an array of bioactive macrocycles with an endo aryl-aryl bond exist in nature. A new palladium catalyzed reaction has been recently developed in which bis(pinacolato)diborane(4) mediated the process to reach such a structural motif. The reaction consists of a domino process involving a Miyaura s arylboronic ester synthesis and an intramolecular Suzuki-coupling. Synthesis of a bicyclic A-B-O-C ring system of RP-66453 273, a neurotensine receptor antagonist, with an endo aryl-aryl and an endo aryl-aryl ether bond was described (Scheme 53).141... 

An approach recently developed by Katritzky et al. which also should be mentioned here, is the palladium-catalyzed reaction of IV-alkylbenzotriazoles with amines, leading to an intramolecular allylic amination route to 2-vinylpyrrolidines and 2-vinylpiperidines in good yield under mild conditions [29]. 

A recent paper explored the 1,2-functionalization of the allene moiety in monocyclic P-lactam allenynol derivatives under palladium-catalyzed reaction conditions <02CEJ1719>. Remarkably, a novel domino process, namely allene cyclization/intramolecular Heck reaction... 

The palladium-catalyzed reaction allowed intramolecular five- or six-membered carbocyclization of diynes and enynes (Equation (40)).245,249 The boryl group was selectively introduced into the more reactive C=CH bond rather than C=C bond of enynes, and into the terminal C=CH bond rather than the internal C=CR bond of diynes. 

In the total synthesis of (-)-conocarpan, the chiral 2,3-dihydrobenzo[b furan core was constructed by radical based intramolecular cyclization as shown below <07CC2151>. In addition, chiral 2-isopropeny 1-2,3-dihydrobenzo[6J furans and 2-amido-bcnzo b furans were be made by palladium-catalyzed reaction in the presence of Trost ligand, and the rhodium(I)-catalyzed cyclization, respectively <07JOC2857 07OL2361>. 

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 reaction of conjugated dienes in the presence of a halide anion can be controlled to give a l-acyloxy-4-halo-2-alkene selectively under appropriate reaction conditions. The catalyst for this system is a palladium(II) salt, usually Pd(OAc)2 or Li2PdCl4. The reaction may be intermolecular or intramolecular. In most cases, it is stereoselective and results in a 1,4-cis addition to the diene. The products obtained from such reactions are useful synthetic intermediates since they have two allylic leaving groups with a large difference in reactivity (see below, under Synthetic applications ). 

Palladium-catalyzed reaction of dienol 80 in acetone in the presence of acetic acid and benzoquinone resulted in an intramolecular 1,4-oxyacetoxylation (Scheme 8-28) [107], The stereochemistry of the reaction can be controlled via a slight variation of the ligand environment. Thus, under chloride-ion-free conditions, a rrawj-oxyacetoxylation occurs. Usually this reaction is highly stereoselective (>98% tram addition), except m = n = 2 in Scheme 8-28, where the tramlcis ratio is 75 25. When the reaction is run in the presence of a catalytic amount of chloride, the stereochemistry is reversed and now a 1,4-cts-oxyacetoxylation takes place. The effect of the chloride is the same as discussed above, i.e., it blocks the coordination of acetate so that cis migration by acetate cannot occur. 

Dilactones can be synthesized by a palladium-catalyzed stereospecific intramolecular double cycliza-tion of 3-hydroxy-4-pentenoic acids (Scheme 21). The cis stereochemistry of the reaction is rationalized by assuming that attack of Pd" on the alkene is directed by the allylic OH group, forming the intermediate (12). 

The second class of substrate of importance bears a CH2 group at one of the termini of the 7t-allyl unit. Until recently this family of substrates presented the biggest challenge because the vast majority of palladium-catalyzed reactions deliver the nucleophile to the less substituted carbon unless there are some special additional factors (i.e., ring size in an intramolecular reaction, substituent effects, etc.). 

Palladium-catalyzed reactions have been used to substitute the isoquinoline ring. With the differential reactivity of the 1- and 3-positions of 1,3-dichloroi.soquinoline regioselective arylation at the 3-position is possible <97JGS(P1)927>. The intramolecular Heck reaction of A-2-bromobenzoyl-1-methylene-1,2,3,4-tetrahydroisoquinoline via a 6-ent/o process provides an entry into the protoberberine ring system <97TL1057>. 

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