Five-membered rings Palladium acetate

Reduction of iV-(3-bromopropyl) imines gives a bromo-amine in situ, which cyclizes to the aziridine. Five-membered ring amines (pyrrolidines) can be prepared from alkenyl amines via treatment with N-chlorosuccinimide (NCS) and then BusSnH. " Internal addition of amine to allylic acetates, catalyzed by Pd(PPh3)4, leads to cyclic products via a Sn2 reaction. Acyclic amines can be prepared by a closely related reaction using palladium catalysts. Three-membered cyclic amines (aziridines)... 

The palladium catalysed substitution reaction of allylic systems has also been utilised in the formation of five membered rings. Intramolecular nucleophilic attack of the amide nitrogen atom on the allylpalladium complex formed in the oxidative addition of the allyl acetate moiety on the catalyst led to the formation of the five membered ring (3.63.). In the presence of a copper(II) salt the intermediate pyrroline derivative oxidized to pyrrole.80... 

The reaction of /V-pentenyl-2-iodoindole in the presence of a palladium-triphenylphosphine catalyst led to the formation of a mixture of isomeric products in good yield (4.8.), Addition of thallium(I) acetate favoured the formation of an exocyclic double bond, while in its absence the product containing the endocyclic olefin moiety is formed preferentially. The shortening of the A-alkenyl chain by one carbon leads to the selective formation of a five membered ring.9 Starting from indole-carboxamide derivatives both /3-. and carbolinones are available in intramolecular Heck coupling. 

By using an olefin embedded into the parent molecule Stoltz developed the oxidative annulation of indoles. The optimal catalyst consisted of palladium acetate and ethyl nicotinate, and molecular oxygen was used as the oxidant in the process. The reaction proceeded equally well irrespective of the attachment point of the alkyl chain bearing the pendant olefin bond on the five membered ring, and the formation of five and six membered rings were both effective (6.95.),127... 

The presence of five-membered rings such as cyclopentanes, cyclopentenes, and dihydrofurans in a wide range of target molecules has led to a variety of methods for their preparation. One of the most successful of these is the use of trimethylenemethane [3 + 2] cycloaddition, catalysed by pal-ladium(O) complexes. The trimethylenemethane unit in these reactions is derived from 2-[ (trimethylsilyl)methyl]-2-propen- 1-yl acetate which is at the same time an allyl silane and an allylic acetate. This makes it a weak nucleophile and an electrophile in the presence of palladium(0). Formation of the palladium 7t-allyl complex is followed by removal of the trimethylsilyl group by nucleophilic attack of the resulting acetate ion, thus producing a zwitterionic palladium complex that can undergo cycloaddition reactions. 

Through an intramolecular alkoxycarbonylation reaction catalyzed by palladium(II), 4-pen-tenc-l,3-diols give tetrahydrofuro[3,2-6]furan-2(3f/)-ones. The reaction is carried out by treating the unsaturated diol with palladium(ll) chloride, copper(ll) chloride and sodium acetate under a carbon monoxide atmosphere. The yields are good and five-membered rings are exclusively obtained with total regioselectivity, as shown by the cyclization of. sj -3-hydroxy-melhyl-5-hexene-l,4-diol (1), which affords only one product in 60% yield44. 

With this bicyclic intermediate available in sizeable amounts, ready advance to 111 could be conveniently accomplished prior to annulation of the second five-membered ring (Scheme XIV). 1,3-Carbonyl transposition was realized by complete eradication of the original carbonyl by Ireland s method [60] followed by allylic oxidation. Application of the Piers cyclopentannulation protocol [61] to 111 made 113 conveniently available. Introduction of a methyl group into ring B was brought about by treatment of the kinetically derived enol triflate [62] with lithium dimethylcuprate [63], Hydrolysis of 114 gave the dienone, which was directly transformed into 115 by oxidation of its silyl enol ether with palladium acetate in acetonitrile [64],... 

In 1997, Gomez, Granell, and Martinez [6] also reported on similarly easy five-membered ring formation. The cyclometalation reactions of imines with palladium acetate have been studied in toluene solutions, as shown in Fig. 6.2. 

By Intramolecular Heck Coupling. l-Bromo-1,5-dienes and 2-bromo-1,6-dienes cyclize in the presence of piperidine and a palladium acetate-tri-o-tolylphosphine catalyst to produce cy-clopentene derivatives (eq 39). 2-Bromo-l,7-octadiene, when subjected to the same reaction conditions, cyclized to yield a mixture of six and five-membered ring products, whereas competing dimerization and polymerization was observed for the more reactive 2-bromo-1,5 dienes. 

Palladium-catalyzed Direct Arylation of Indoles and Thiophenes. Five-membered ring heterocycles possessing only one heteroatom and no Af-oxide function can also be arylated using palladium(II) complexes, a phosphine ligand, and an inorganic base. In one example, a tandem palladium-catalyzed Heck coupling reaction and direct intramolecular C2 arylation reaction on a )V-(2-chlorobenzyl)-5-bromoindole was reported (eq 30). The procedure, which is catalyzed by palladium acetate, uses tn-tert-butylphosphonium tetrafluoroborate as a ligand and ferf-butyl acrylate as the alkene for the Heck reaction (eq 30). ... 

The synthesis of five-membered carbo- and hetero-cyclic compounds, including fused rings, has been reported using acetate as a nucleophile in the cyclization of 1,6-enynes under palladium(II) catalysis (Scheme 91). The reaction is initiated by trans-acetoxypalladation of the alkynes and quenched by either trans- or ra-deaceloxypal-ladation in the presence of 2,2/-bipyridine as the ligand.134... 

Jt-allyl complex can be generated after cyclization, as suggested by Takacs in a Fe(0)-catalyzed cyclization of polyenes. It also can be preformed if an active functional group is present in the allylic position. The palladium-catalyzed intramolecular cycloisomerization reaction of allylic acetates is an efficient method for constructing five- or six-membered rings [56, 57]. An asymmetric approach to this transformation has been studied and so far only poor enantioselectivity has been achieved (0-20% ee) [58]. Very recently, Zhang et al. also reported a Rh-catalyzed cycloisomerization involving a Jt-allylrhodium intermediate formed from an allylic halide [59]. 

This method was utilized in the preparation of bicyclic compounds consisting of five-, six-, and seven-membered rings. Oxidative addition of allylic acetates to palladium(O) takes place with inversion of configuration and intramolecular alkene insertion into the... 

By Cycloaddition. Palladium acetate, combined with (i-PrO)3P, catalyzes the [2 + 3] cycloaddition of trimethylen-emethane to alkenes carrying electron-withdrawing substituents (eq 50). The yields of five-membered carbocycle varied from 35-89%. With 1,3-dienes, a [4 + 3] cycloaddition gave seven-membered ring products in good yield (eq 51), and in some cases excellent diastereomeric ratios were observed. 

C-H Activation. Tri-terf-butylphosphine, combined with palladium acetate, acts as an effective catalytic system for the direct Ar-H arylation of heterocycles. This system has been applied for the functionalization of various five- and six-membered ring heterocycles containing one or more heteroatoms. A base (CS2CO3,... 

The palladium-catalyzed carbocyclization of allylic acetates with alkenes is a powerful method for the formation of five- and six-member rings. The reaction initiates throngh the formation of a rt-aUyl palladium complex followed by carbometaUation of the second double bond. The formed palladium complex is then eliminated to produce commonly the cyclized 1,4-dienes (Scheme 7.48). 

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