Alkenylpalladium intermediates

A highly diastereoselective alkcnylation of c/s-4-cyclopentene-l,3>diols has been achieved with 0-protected (Z)-l-iodo-l-octen-3-ols and palladium catalyst (S. Torii, 1989). The ( )-isomers yielded 1 1 mixtures of diastcrcomcric products. The (Z)-alkenylpalladium intermediate is thought to undergo sy/i-addition to the less crowded face of the prochiral cyclopentene followed by syn-elimination of a hydropalladium intermediate. 

The alkenylpalladium intermediate 364, formed by the intramolecular insertion of 363, is terminated by hydrogenolysis with formic acid to give the terminal alkene 365[266]. The intramolecular insertion of 366 is terminated by the reaction of the alkynylstannane 367 to afford the conjugated dienyne system 368[267j. 

As shown in the previous sections, a (cr-allenyl)palladium species, which is formed from a propargyl electrophile and a Pd(0) catalyst, reacts with a hard carbon nucleophile in a manner analogous to the Pd-catalyzed cross-coupling reaction to give a substituted allene. The results indicate that the reactivity of the (cj-allenyl)palladium species is similar to that of an alkenylpalladium intermediate. Indeed, it was found that the (cr-allenyl)palladium species reacted with olefins to give vinylallenes, a reaction process that is similar to that of the Heck reaction of alkenyl halides [54]. 

The formation of compound 175 could be rationalized in terms of an unprecedented domino allene amidation/intramolecular Heck-type reaction. Compound 176 must be the nonisolable intermediate. A likely mechanism for 176 should involve a (ji-allyl)palladium intermediate. The allene-palladium complex 177 is formed initially and suffers a nucleophilic attack by the bromide to produce a cr-allylpalladium intermediate, which rapidly equilibrates to the corresponding (ji-allyl)palladium intermediate 178. Then, an intramolecular amidation reaction on the (ji-allyl)palladium complex must account for intermediate 176 formation. Compound 176 evolves to tricycle 175 via a Heck-type-coupling reaction. The alkenylpalladium intermediate 179, generated in the 7-exo-dig cyclization of bro-moenyne 176, was trapped by the bromide anion to yield the fused tricycle 175 (Scheme 62). Thus, the same catalytic system is able to promote two different, but sequential catalytic cycles. 

Alkenyl halides and their pseudohalides also react with Pd(0) to form the alkenylpalladium intermediates 11, and their transformations are summarized in Scheme 3.4. In addition to alkenyl halides, the enol triflates 12 undergo oxidative addition, showing that carbonyl compounds are useful starting compounds for Pd-catalysed reactions. 

The alkyne insertion reaction is terminated by anion capture. As examples of the termination by the anion capture, the alkenylpalladium intermediate 189, formed by the intramolecular insertion of 188, is terminated by hydrogenolysis with formic acid to give the terminal alkene 192. Palladium formate 190 is formed, and decarboxylated to give the hydridopalladium 191, reductive elimination of which gives the alkene 192 [81]. Similarly the intramolecular insertion of 193 is terminated by transmetallation of 194 with the tin acetylide 195 (or alkynyl anion capture) to give the dienyne 196 [82], Various heterocyclic compounds are prepared by heteroannulation using aryl iodides 68 and 69, and internal alkynes. Although the mechanism is not clear, alkenylpalladiums, formed by insertion of alkynes, are trapped by nucleophiles... 

An early example having potential commercial importance comes from tlie Trost laboratory s synthesis of vitamin D analogs (Scheme 6-23) [51], Their combination of vinyl bromide 129 and alkyne 130 to form triene 131 led to a concise and efficient synthesis of (-i-)-alphacalcidiol (134). In this reaction, vinyl bromide 129 participates in a bimolecular Heck reaction with alkyne 130 and the resulting alkenylpalladium intermediate 133 undergoes subsequent intramolecular Heck reaction with the pendant terminal alkene to provide 131. Under the reaction conditions, some of the desired product undergoes a [1,7]-hydrogen shift to yield 132. After thermal recycling of the minor component, a remarkable 76% yield of 131 was obtained. 

The introduction of an o-methoxy group on the benzene ring of the alkynyl substituent increased the yields of the cyclization products. The reaction proceeds through the nucleophilic attack of the nitrogen atom on electron-deficient alkyne 317, the formation of the alkenylpalladium intermediate 318, the insertion of the alkenes 315 into the C—Pd bond 319, and -hydride elimination. They reported many examples of this type of reactions, but those are summarized in their own review in this issue of Chemical Reviews.168... 

Scheme 51. (a) Enyne metathesis to form five-membered products using Pd(0). (b) Mechanism illustrating the formation of an unusual alkenylpalladium intermediate via a n-allylpalladium species. 

Aminocarbonylation of the aryl and alkenyl iodides 85 with DMF proceeds via nucleophilic attack of the aryl- and alkenylpalladium intermediates 88 [46]... 

Another important Pd(II)-generation step is protonolysis with acids. For example, alkenylpalladium intermediates formed by palladation of alkynes with... 

Alkenyl halides undergo similar transformations. In addition to alkenyl halides 13, alkenyl triflates 15 and phosphates 16, derived from aldehydes and ketones, are useful pseudohalides, that undergo oxidative addition to form alkenylpalladium intermediates 14. Typical examples of insertion of unsaturated bonds to 14 are shown in Scheme 3.5. 

Arylation is not limited to aryl halides. Alkenylpalladium intermediates, formed in situ in domino reactions of polyenynes, attack aromatic rings. The intermediate 11 is generated by 5-exo cyclization of the iodide 10a. Then cyclization occurs to give 12 by attack of the alkylpalladium species on furan in 11, because the alkylpalladium has no possibility of elimination [7]. 

Intramolecular arylation of 28 and 29 occurred at either C-2 or C-3 to give 30 and 31 when the C-3 or C-2 position is substituted [11], The alkenylpalladium intermediate 33, generated by the reaction of the bis-indole 32 with an alkyne as a relay, attacks the indole to give 34 [12],... 

Scheme 3.7 Intermolecular transformations of aryl- and alkenylpalladium intermediates 2...

MeCN is a good and inert solvent used in various Pd-catalyzed reactions. However, nitriles participate in Pd-catalyzed intramolecular reactions. The indenone 43 was obtained by the reaction of o-iodobenzonitrile (40) with alkynes. The reaction can be understood by insertion of a nitrile bond to alkenylpalladium intermediate 41 or 5-exo cyclization to give the iminopalladium 42, hydrolysis of whieh affords the indenone 43 and Pd(II), which is reduced to Pd(0) [4]. 

The isoquinoline 61 was obtained by the reaction of t-butylimine 60 of 0-iodobenzaldehyde with internal alkyne [20], The reaction was extended to synthesis of the y-carboline 65 from the r-butylimine of A -methyl-2-iodoindole-3-carboxaldehyde 62 [21], The reaction is explained by 6-endo cyclization of the alkenylpalladium intermediate 63, followed by elimination of /i-t-butyl group as isobutylene as shown by 64. This mechanism explains the importance of t-butylimine in this cyclization. 

The pyran 88 and a-pyrone 90 are prepared from the vinyl bromide 87 and the vinyl triflate 89 by intramolecular trapping of the alkenylpalladium intermediates with alcohol and ester [29,30]. The pyridine 92 was prepared by the iminoannula-tion of the iminoalkenyl iodide 91 [31]. The 2-iodo-3-tosylaminocyclohexene 93 underwent CM -carboaminadon of ethyl phenylpropiolate to give 94 [32]. 

However, reaction of dianisylacetylene under similar eonditions afforded a mixture of the regioisomers 176a and 176b. The result shows that cis-trans isomerization of the alkenylpalladium intermediate becomes possible due to the eontribution of 177 which can rotate [58],... 

Furthermore, the reaction of diphenylacetylene with iodobenzene under Jeffery conditions gave rise to 9-alkylidene-9H-fluorene 178. The reaction is explained by a novel migration of the alkenylpalladium intermediate 179 to the arylpalla-dium species 180. Finally 178 is formed via the palladacycle 181 and reductive elimination [59]. 

Pd-catalyzed and promoted reactions of allenes can be classified into three groups. The first one is promoted by Pd(II). For example, aminopalladation of hexa-l,2-dienyl-6-amine with Pd(II) generates the alkenylpalladium intermediate 52, which is converted to functionalized alkene 53 with generation of Pd(0). In order to make the reaction catalytic, Pd(0) has to be oxidized to Pd(II) with some oxidants. This type of reaction is treated in Chapter 2.5. 

On the other hand, an alkenylpalladium intermediate formed by intramolecular carbopalladation from a 2-bromo-l-en-6-yne carbopalladates an external mono-or disubstituted alkyne, and the cascade process is terminated by cyclization of the 1,3,5-hexatrienylpalladium intermediate through intramolecular carbopalladation or 67T-electrocyclization and ensuing dehydropalladation (Scheme... 

Under yet different conditions, the carbopalladation product from an alkenylpalladium intermediate undergoes a 3-exo-trig cyclization and subsequent /3-hydride elimination leading to a 2,3-methanobicyclo[2.2.1]heptane derivative (Scheme 50). "... 

Besides these alkylations of soft nucleophiles with cr-alkenylpalladium intermediates, 7T-allylpalladium complexes, formed by carbopalladation of an allene with an arylpalla-dium halide intermediate, are able to cyclize by attacking a dialkyl malonate moiety (Scheme 20)P° Instead of allenes, which give methyleneindane derivatives, cyclic and acyclic 1,4-dienes have been employed to yield tetrahydronaphthalene derivatives in good yieldsl ... 

Insertion of alkynes into Pd-P bonds give alkenylpalladium intermediates 2 and 3. Photonolysis of these intermediates by diaUcyl H-phosphonate results in aUcenylphospho-nates 4 and 5 and regenerates the active catalyst 1. Indirect evidence for the insertion of alkynes into Pd-P bonds comes from the isolation of trace amounts of alkynyl phospho-nate 6, which can only result from reductive elimination of the alkenylpalladium intermediate 3. The second hydrophosphorylation reaction proceeds via the insertion of geminal alkenylphosphonate 4 into the Pd-H bonds, followed by reductive elimination of the product 7. This reaction pathway can explain the failure of 5 to react with dialkyl H-phosphonate because of the steric hindrance of the potential insertion intermediate. These bisphosphonates are evalnating as ligands for radionuclides such as and for... 

Catalytic carbopalladation is a ubiquitous process and alkynes are viable substrates. Alkenyl tellurides couple efficiently with alkynes with retention of the double bond geometry. Relatively large amounts of palladium catalyst are required.Oxidative dimerization of monoterpenes has been assumed to involve alkenylpalladium(ii) intermediates. Alkenylpalladium(ii) and di(alkenyl)palladium(iv) complexes have been put forward as intermediates in a similar reaction of halogenoterpenes. The subject has been reviewed concerning the formation of heterocycles by intramolecular cyclization of intermediate alkenylpalladium intermediates. ... 

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