Intramolecular insertions, alkenes

Unlike the intermolecular reaction, the intramolecular aminopalladation proceeds more easily[13,14,166], Methylindole (164) is obtained by the intramolecular exo amination of 2-allylaniline (163). If there is another olefinic bond in the same molecule, the aminopalladation product 165 undergoes intramolecular alkene insertion to give the tricyclic compound 166[178]. 2,2-Dimethyl-l,2-dihydroquinoline (168) is obtained by endo cyclization of 2-(3,3-dimethyiallyl)aniline (167). The oxidative amination proceeds smoothly... 

The silyl enol ethers 209 and 212 are considered to be sources of carbanions. and their transmetallation with Pd(OAc)2 forms the Pd enolate 210. or o.w-tt-allylpalladium, which undergoes the intramolecular alkene insertion and. 1-elimination to give 3-methylcyclopentenone (211) and a bicyclic system 213[199], Five- and six-membered rings can be prepared by this reaction[200]. Use of benzoquinone makes the reaction catalytic. The reaction has been used for syntheses of skeletons of natural products, such as the phyllocladine intermediate 214[201], capnellene[202], the stemodin intermediate 215[203] and hir-sutene [204]. 

The acylpalladium complex formed from acyl halides undergoes intramolecular alkene insertion. 2,5-Hexadienoyl chloride (894) is converted into phenol in its attempted Rosenmund reduction[759]. The reaction is explained by the oxidative addition, intramolecular alkene insertion to generate 895, and / -elimination. Chloroformate will be a useful compound for the preparation of a, /3-unsaturated esters if its oxidative addition and alkene insertion are possible. An intramolecular version is known, namely homoallylic chloroformates are converted into a-methylene-7-butyrolactones in moderate yields[760]. As another example, the homoallylic chloroformamide 896 is converted into the q-methylene- -butyrolactams 897 and 898[761]. An intermolecular version of alkene insertion into acyl chlorides is known only with bridgehead acid chlorides. Adamantanecarbonyl chloride (899) reacts with acrylonitrile to give the unsaturated ketone 900[762],... 

Butyrolactones are prepared by intramolecular reaction of haloallylic 2-alkynoates. The a-chloromethylenebutyrolactone 301 is prepared by the intramolecular reaction of300[150,151]. 4 -Hydroxy-2 -alkenyl 2-alkynoates can be used instead of haloallylic 2-alkynoates, and in this reaction, Pd(II) is regenerated by elimination of the hydroxy group[152]. As a related reaction, the q-(chloromethylene)-7-butyrolactone 304 is obtained from the cinnamyl 2-alkynoate 302 in the presence of LiCl and CuCbflSS]. Isohinokinin (305) has been synthesized by this reaction[l 54]. The reaction is explained by chloro-palladation of the triple bond, followed by intramolecular alkene insertion to generate the alkylpalladium chloride 303. Then PdCb is regenerated by attack of CuCb on the alkylpalladium bond as a key step in the catalytic reaction. 

Oxypalladation of vinyl ether, followed by alkene insertion, is an interesting synthetic route to functionalized cyclic ethers. In prostaglandin synthesis, the oxypalladation of ethyl vinyl ether (40) with the protected cyclopentenediol 39 generates 41 and its intramolecular alkene insertion generates 42. The intermolecular insertion of the alkene 43, and /1-elimination of 44 occurred as one-pot reaction at room temperature, giving the final product 45 in 72% yield [46], The stereochemistry of the product shows that the alkene insertion (carbopalladation of 41) is syn. It should be noted that the elimination of /1-hydrogen from the intermediate 42 is not possible, because there is no /1-hydrogen syn coplanar to the Pd and, instead, the insertion of alkene 43 occurs. 

Another type of carbopalladation is observed in the oxidation of the 2,2-disubstituted alkene attached to the cyclobutanol 104. The shift of the carbon-carbon bond as shown by 105 and ring expansion generate 106. Intramolecular alkene insertion gives the bicyclo[4.3.0]nonane system 107. Finally, 108 is obtained [78],... 

Dimethylbutadiene)HfCp (Cl)] (74c) reacts with one molar equivalent of acetylene to yield the unusual product 87. This is probably formed by a conventional butadiene/alkyne coupling at the Group 4 metal center, followed by an intramolecular alkene insertion into the adjacent hafnium to carbon cr-bond. The resulting alkylidene complex (86) then rapidly dimerizes to yield the observed final product (see Scheme 28), that was characterized by X-ray diffraction.96... 

Besides enyne metathesis [66] (see also the chapter Recent Advances in Alkenes Metathesis in this volume), which generally produces 1-vinylcyclo-alkenes, ruthenium-catalyzed enyne cycloisomerization can proceed by two major pathways via hydrometallation or a ruthenacycle intermediate. The RuClH(CO)(PPh3)3 complex catalyzed the cyclization of 1,5- and 1,6-enynes with an electron-withdrawing group on the alkene to give cyclized 1,3-dienes, dialkylidenecyclopentanes (for n=2), or alkylidenecyclopentenes (for n= 1) [69,70] (Eq. 51). Hydroruthenation of the alkyne can give two vinylruthenium complexes which can undergo intramolecular alkene insertion into the Ru-C bond. 

A stepwise sequence of nucleophilic addition to the complexed norbomadiene followed by intramolecular alkene insertion was first observed with dichloro(norbornadiene)palla-dium(II) which, upon addition of methanol, only forms the normal adduct 11. Subsequent conversion with l,2-bis(triphenylphosphanyl)ethane (dppe), however, gave the nortricyclene complex 12. Reductive displacement of the alkyl ligand with lithium aluminum hydride or oxidative cleavage with halogens gave noncomplexed nortricyclene derivatives. ... 

Norbornadiene complexes of platinum and palladium 14 reacted with silver carboxylates to form the carboxymetalation products 15 which, on treatment with triphenylphosphane, underwent intramolecular alkene insertion to form the nortricyclene skeleton 16. Reductive decom-plexation gave the acylated tricyclo[2.2.1.0 ]heptan-ex n-3-ol 17. ... 

As a reverse of fi-C elimination in methylcyclopropane complexes to form homoallyl systems, homoallylmetal complexes can undergo intramolecular alkene insertion to yield metallated methylcyclopropanes. 

Cyclopropanation of norbornene (9) with vinyl halides benzyl halides " or alkynes is also interpreted as proceeding via homoallylmetal complexes 10 and intramolecular alkene insertion to form the tricyclic product 11. 

Formation of cyclopropane-containing oligocyclic systems such as nortricyclenes from nor-bornadienes also proceed via intramolecular insertion of homoallylmetal complexes. Palladated nortricyclene 19 can be converted with lithium aluminum hydride, chlorine or bromine to give 3-exo-methoxynortricyclene (20) and the en(/o-3-halo-exo-5-methoxy analogs 21 and 22, respectively. Intramolecular alkene insertion into the Pd — C bond is assumed to form the nortricyclene skeleton. ... 

In more complex reaction cascades an additional alkyne-insertion step can occur. Thus starting with intramolecular carbopalladation of a vinyl iodide to a carbon-carbon triple bond, followed by two intramolecular alkene-insertion steps and termination with dehydropalladation, a palladium-catalyzed synthesis of l-(5 -methylbicyclo[3.1.0]hex-T-yl)-5,5-bis(carboethoxy)cyclo-hexadiene (52) starting from l-iodo-4,4-bis(carboethoxy)-ll-methyldodeca-l,ll-dien-6-yne (51) is achieved. ... 

Yamamoto et al. found that benzyne and methallyl chloride 273 underwent an interesting 2 1 cycloaddition to afford the phenanthrenes 274 and 275 using phosphine-free Pd2(dba)3 [86], This novel reaction is explained by the following mechanism. First, insertion of benzyne to jr-allylpalladium generates 276, which undergoes the insertion of benzyne again to give 277. Subsequent intramolecular alkene insertion, and jS-H elimination provide 278, and then 279. 

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

The Pd-catalyzed cycUzation of alkenyl- and alkynyl-tethered allylic acetates gives a-alkyl- and alkenylpalladium intennediates, respectively, which can undergo further intramolecular alkene insertion, carbonylation, and transmetallation, respectively, to form additional carbon-carbon bonds (Scheme 8), as exemplified for such cascade reactions with insertion of a tethered alkene in Scheme 12.E3],[24H27]... 

Allylpalladation of alkenes, alkynes, and dienes is a powerful tool for preparing carbocy-cles and heterocycles. The combination of allylpaUadations with intramolecular alkene insertion, carbonylation, and transmetaUation in cascade-type sequences demonstrates the high potential of these Pd-catalyzed cycUzation reactions for the synthesis of complex... 

Several other types of domino reactions have been employed in the synthesis of natural products. Diastereoselective conversion of allylic carbonate 173 into enone 174 was one key transformation in a total synthesis of (+)-3-isorauniticine 175 (Scheme 27).Treatment of allylic sulfonamide 173 with a palladium catalyst re-gioselectively forms a 7r-allylpalladium intermediate by carbonate displacement. Carbopalladation of the pendant alkene, carbonylation, a second intramolecular alkene insertion, and /3-hydride elimination delivers a 67 22 11 mixture of stereoisomers of which enone 174 is the major product (isolated in 45-53% yield). Carbopalladation products can also undergo anion capture reactions. For instance, during the synthesis... 

Abelman, M.M., Overman, L.E. and Tran, V.D. (1990) Construction of quaternary carbon centers by paUadium-catalyzed intramolecular alkene insertions. Total s3uithesis of the Amarylh-dacea alkaloids ( )-tazettine and ( )-6a-epipretazettine. J. Am. Chem. Soc., 112, 6959 4. 

In a seminal communication, Chiusoh et al. reported an example of an intercepted Mizoroki-Heck reaction for the first time [86]. A palladiumreducing agent, ammonium formate, produced a mixture of 146 and 147 in a reaction temperature-dependent ratio (Scheme 7.34). The minor product 147 was formed by standard intermolecular Mizoroki-Heck alkenylation and subsequent reductive cleavage of the intermediate C(sp )—Pd" bond formation of the major product 146 involved an additional intramolecular alkene insertion prior to the reduction step. 

The intramolecular Heck reaction is a powerful method for ring formation. Depending on the substrate structure, the question of exo- or endo-fmg formation may need to be addressed (Scheme 5.31). In principle, intramolecular alkene insertion can yield either the cxo-product 5.101 or the enr/b-product 5.103. Generally, the xo-product 5.101 is obtained. 

A three-component coupling involving three alkenes was employed using a stoichiometric amount of palladium to generate a bicyclic acetal 6.91, which could be converted to an epimer of the prostaglandin, PGF2 (Scheme 6.31). The three-component coupling involves nucleophilic attack of the alcohol 6.89 onto an ethyl vinyl ether-palladium complex 6.93, intramolecular alkene insertion, intermolecular insertion of... 

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