Hydride sources palladium

Hydrogenolysis of aryl and alkenyl halides and triflates proceeds by the treatment with various hydride sources. The reaction can be explained by the transmetallation with hydride to form palladium hydride, which undergoes reductive elimination. Several boro hydrides are used for this purpose[680], Deuteration of aromatic rings is possible by the reaction of aryl chlorides with NaBD4681]. 

Formic acid behaves differently. The expected octadienyl formate is not formed. The reaction of butadiene carried out in formic acid and triethylamine affords 1,7-octadiene (41) as the major product and 1,6-octadiene as a minor product[41-43], Formic acid is a hydride source. It is known that the Pd hydride formed from palladium formate attacks the substituted side of tt-allylpalladium to form the terminal alkene[44] (see Section 2.8). The reductive dimerization of isoprene in formic acid in the presence of Et3N using tri(i)-tolyl)phosphine at room temperature afforded a mixture of dimers in 87% yield, which contained 71% of the head-to-tail dimers 42a and 42b. The mixture was treated with concentrated HCl to give an easily separable chloro derivative 43. By this means, a- and d-citronellol (44 and 45) were pre-pared[45]. 

A synthesis of (-)-4a,5-dihydrostreptazolin was accomplished in a similar manner only a reductive palladium-catalyzed cyclization was utilized.104 The hydride source was polymethylhydroxysilane (PMHS), and the unprotected hydroxyl group of 174 (Equation (89)) had an accelerating effect, since the reaction was completed in minutes instead of hours, as in the example above. 

Equations 12, 14 and 17 require the presence of H20. Thus H20 plays an important role in promoting the catalytic activity, but can also cause deactivation. Catalysis will be more efficient when all the reactions directly involved in the catalytic cycle are faster than the side reactions subtracting active species. Deactivation is related to the requirement of the palladium centre to have a vacant coordination site to ensure high catalytic activity. However, palladium tends to achieve the usual coordination number four, for example through dimerisation. Dimerisation/deactivation can be prevented by coordination of labile ligands, like H20, which acts also as an efficient hydride source. Also deprotonation leads to dimerisation/deactivation an acid can prevent it. 

Esters of allylic alcohols with resin-bound carboxylic acids can be converted into allyl palladium complexes, which react with carbon nucleophiles and with hydride sources to yield the formally reduced allyl derivatives (Entries 3 and 4, Table 3.47). Alkyl sulfonates have been reduced to alkanes with NaBH4 (Entry 5, Table 3.47). Aryl sulfonates (Entry 6, Table 3.47) and aryl perfluoroalkylsulfonates [814] can be reduced to alkanes by treatment with catalytic amounts of Pd(II) and formic acid as a hydride source. 

Pd-mediated coupling of 50 could, in principle, terminate via p-elimination of either the C8 or C12 hydrogens. However, only the latter was observed. In our case, pentacycle 46 has only the C8 hydrogen available, and the normal course of the Heck reaction would be expected to produce pyridone 58 (Scheme 30). If p-elimination proved slow, an added hydride source might capture the palladium a-complex and provide the desired formal conjugate addition product 51. 

As shown in Scheme 5.1, formic acid behaves differently to other carboxylic acids. Expected octadienyl formate is not formed. The reaction with formic acid in the presence of EtjN affords 1,7-octadiene (140) [62 64], The first step is the protonation of bis-Ji-allylpalladium 68 with formic acid to generate 167. Formic acid is a hydride source, ft is known that the Pd hydride, formed by the decarboxylation of palladium formate, attacks the substituted side of 7i-allylpalladium as shown by 167 to form the terminal alkene 140 [65], The regioselective attack of Pd—H at the more substituted side of 7r-allyl systems is covered in Section 4.3.7. 

Hydrogenolysis over Palladium with Other Hydride Sources... 

The synthesis of aromatic aldehydes from aryl halides, carbon monoxide, and a hydride source has also been studied, but practical procedures for this process have been published only recently. Thus, the presentation of this process will be brief. The original formyla-tions of aryl halides were conducted with a tin hydride, as shown in Equation 19.88, or a silicon hydride. More recently, reactions were reported with formate as the hydride source (Equation 19.89). In fact, one of the earliest palladium-catalyzed reactions of aryl chlorides was the fonnylation of an aryl chloride to form aromatic aldehydes using... 

C. PALLADIUM-CATALYZED HYDROGENOLYSIS WITH OTHER HYDRIDE SOURCES... 

Pd-catalyzed hydrogenolysis of allylic compounds with formates is an efficient and mild method. The hydride generated from the palladium formate attacks the more substimted side of the allylic system to give less substituted olefins in contrast to the case with other hydride sources. Pd-catalyzed hydrogenolysis of propargylic compounds affords either aUenes or alkynes depending on the structure of the propargylic compounds. 

However, in reviewing the literature of the last two decades the application of Pd-catalyzed formylations to the more difficult substrates is showing promise. By finding the appropriate hgand or hydride source the difficult step(s) in the reaction pathway can be overcome. Bimetallic catalysis exploits the synergistic effect of metals. For example, where palladium works well in the oxidative addition or complexation to a double bond, the added metal can aid in transfer of the CO or hydride. It is certain that the deficiencies of the Pd-catalyzed hydroformylation will be overcome in time. 

The main steps in the currently accepted catalytic cycle of the Heck reaction are oxidative addition, carbopalla-dation (G=G insertion), and / -hydride elimination. It is well established that both, the insertion as well as the elimination step, are m-stereospecific. Only in some cases has formal /r/ / i--elimination been observed. For example, exposure of the l,3-dibromo-4-(dihydronaphthyloxy)benzene derivative 16 and an alkene 1-R to a palladium source in the presence of a base led to a sequential intra-intermolecular twofold Heck reaction furnishing the alkenylated tetracyclic products 17 in good to excellent yields (Scheme 9). " In the rate-determining step, the base removes a proton in an antiperiplanar orientation from the benzylic palladium intermediate. The best amine base was found to be l,4-diazabicyclo[2.2.2]octane, which apparently has an optimal shape for this proton abstraction. 

An important modification of the initial protocol has been introduced by Larock ef al. to afford indanones. The saturated ring results from the termination of the process by protonolysis of palladium enolate, which is likely to be generated from reversible palladium hydride elimination-addition. Proton source required for protonolysis hypothetically comes from adventitious water coming with hygroscopic chloride or solvent (Scheme 13). ... 

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