Ring closures carbopalladative

Five-membered ring closures have been observed when o-halostyrene derivatives such as 113 were coupled with alkenes under palladium catalysis. Apparently, an intramolecular carbopalladation with S-exo-trig ring closure to give 114-R can favorably compete with / -hydride elimination in the first-formed intermediate to yield 115-R This reaction mode for the halostyrene is observed especially under Jeffery conditions, when the alkene is ethene or propene (Scheme 31). Under the same conditions, however, < -dibromobenzene gives very high yields of o-dialkenylbenzene derivatives (see Scheme 2). ... 

Zhao and Larock have introduced a convenient method for the preparation of substituted dibenzofurans as well as carbazoles and indoles by palladium-catalyzed cross-coupling of alkynes and appropriately substituted aryl iodides. These reactions proceed by carbopalladation of the alkyne, heteroatom-directed migration of palladium from a vinyl to the adjacent aryl position, and ring closure via intramolecular arylation (Scheme 87) <2006JOC5340>. 

The comparison of intramolecular carbopalladation reactions of allenes and alkenes outlined in Schemes 9-5 and 9-6 illustrates that not every transition metal catalyzed ring closure necessarily involves a template effect. Others, however, clearly benefit from it. A prototype example is the palladium catalyzed cycloisomerization of alkenyl epoxides carrying distal pre-nucleophiles [38, 39], representing one variant of the famous Tsuji-Trost allylation [40]. 

Intramolecular carbopalladation has widely been used to assemble the polycyclic frameworks of natural products. The majority of these carbopalladations are intramolecular Heck reactions and examples of 5-exo, 6-exo, 1-exo, -exo, 6-endo, S-endo, and macro-cyclic ring closures will be presented (Scheme 12). Examples fall into two basic categories vinylic substitution (75- 76) and quaternary center construction (77- 78). Investigation of domino reactions like polyene cyclizations (79- 80) and asynunetric Heck reactions (81 82) has been fruitful. 

Ali and Alper later developed a method for y-lactone formation under neutral conditions from allylic alcohols according to Scheme 23, involving Pd(0) and dppb. The same protocol was also applied to synthesis of a,/3-butenolides from propargylic alcohols. Other bidentate or monodentate ligands give inferior results, and this correlates well with bite angle effects on the rate of the CO insertion reaction. Also, the allylic alcohol needs to be a-alkyl substituted to facilitate ring closure, in accordance with other studies.t t This process was postulated by the authors to be of the carbopalladative type. 

Five-membered ring closure has been observed when < -halostyrene derivatives were coupled with alkenes under palladium catalysis.t Apparently an intramolecular carbopalladation... 

As shown in Scheme 6.37, some transition-metal-assisted ring-closure reactions of 1,2-diethynylbenzenes afford dibenzopentalene derivatives unexpectedly. Diederich s group designed a carbopalladation cascade reaction of easily accessible ew-dibromoolefins 286 and alkynes to furnish monobenzo-287 and mononaphthopentalenes 288 (Scheme 6.72). This successful methodology allows the preparation of asymmetrically substituted pentalene derivatives with only one fused aromatic system [167]. 

Alike olefins, allenes also undergo palladium mediated addition in the presence of N-H or O-H bonds. Although these reactions show some similarity to Wacker-type processes, from the mechanistic point of view they are quite different. Allenes, such as the cr-aminoallene in 3.69., usually undergo addition with palladium complexes (e.g. carbopalladation in 3.69. and 3.70., or hydropalladation in 3.71.), which leads to the formation of a functionalized allylpalladium complex. Subsequent intramolecular nucleophilic attack by the amino group leads to the closure of the pyrroline ring.87... 

Tethering an iodobenzene and a furane moiety through a y0-lactam led to the formation of a unique tetracyclic y0-lactam derivative (5.17.). Oxidative addition followed by the carbopalladation of the furane ring resulted in the closure of the seven membered core in a so called heteroaryl Heck reaction "... 

Carbopalladation has also been employed in the construction of six-membered rings. Most examples are 6-exo cyclizations as is the pyran ring synthesis (107—>108) used in the construction of ( )-6a-epipretazettine 109 and ( )-tazettine (Scheme 17). The Heck cyclization formed a quaternary center with a diastereoselectivity in excess of 20 1. The selectivity of the reaction is of particular interest in this case as it provides information about the orientation of the carbon-palladium a bond and the reacting aUcene in the carbopalladation transition state. Two limiting transition state geometries for the closure are intermediate 110, which leads to the observed product, and intermediate 111, which would lead to a diastereomer. In the preferred transition state 110, the carbon-palladium (7 bond and alkene are eclipsed, which is a lower energy state than the corresponding twisted orientation 111. 

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