Palladium-catalyzed oxidative addition

Synthesis of heterocycles via palladium-catalyzed oxidative addition 06CRV4644. 

Zeni, G. and Larock, R.C. (2006) Synthesis of heterocycles via palladium-catalyzed oxidative addition. Chem. Rev., 106, 4644-80. 

Interestingly, this Heck-type palladium-catalyzed oxidative addition/insertion manifold can also be applied to the actual formation of the carbon-heteroatom bond. This was illustrated by Narasaka in the reaction of olefin-tethered oxime derivatives. This chemistry can be considered to arise from oxidative addition of the N—O bond to palladium (30) followed by the more classical olefin insertion and (3-hydride elimination, ultimately allowing the assembly of pyrroles (Scheme 6.58) [79]. The nature of the OR unit was found to be critical in pyrrole formation, with the pentafluorobenzoylimine leading to selective cyclization and rearrangement to the aromatic product. An analogous approach has also been applied to pyridines and imidazoles [80]. 

The 5-oxohexanal 27 is prepared by the following three-step procedure (1) 1,2-addition of allylmagnesium bromide to an a, / -unsaturated aldehyde to give the 3-hydroxy-1,5-diene 25, (2) oxy-Cope rearrangement of 25 to give 26, and (3) palladium catalyzed oxidation to afford 27. The method was applied to the synthesis of A -2-octalone (28), which is difficult to prepare by the Robinson annulation[25]. 

As mentioned above nonconjugated dienes give stable complexes where the two double bonds can form a chelate complex. A common pathway in palladium-catalyzed oxidation of nonconjugated dienes is that, after a first nucleophilic addition to one of the double bonds, the second double bond inserts into the palladium-carbon bond. The new (cr-alkyl)palladium complex produced can then undergo a /(-elimination or an oxidative cleavage reaction (Scheme 2). An early example of this type of reaction, although not catalytic, was reported by Tsuji and Takahashi (equation 2)12. 

Attempts to employ allenes in palladium-catalyzed oxidations have so far given dimeric products via jr al lyI complexes of type 7i62.63. The fact that only very little 1,2-addition product is formed via nucleophilic attack on jral ly I complex 69 indicates that the kinetic chloropalladation intermediate is 70. Although formation of 70 is reversible, it is trapped by the excess of allene present in the catalytic reaction to give dimeric products. The only reported example of a selective intermolecular 1,2-addition to allenes is the carbonylation given in equation 31, which is a stoichiometric oxidation64. 

In addition to the aforementioned total syntheses. Shannon et al. observed the formation of an N-C3-linked dimer during the transformation of a 3-bromocarbazole to a 3-cyanocarbazole by reaction with copper(I) cyanide in DMF under reflux (668). Harrity et al. reported the synthesis of non-natural (+ )-N,N -dimethylbismurrayafoline A via a chromium-mediated benzannulation, followed by a palladium-catalyzed oxidative coupling reaction (669). 

T[[dotb]he nature of the initial attack by the water (eq. 10) is a matter of some controversy (205,206). Stereochemical and kinetic studies of model systems have been reported that support trans addition of external water (207,208) or internal addition of cis-coordinated water (209), depending on the particular model system under study. Other palladium-catalyzed oxidations of olefins in various oxygen donor solvents produce a variety of products including aldehydes (qv), ketones (qv), vinyl acetate, acetals, and vinyl ethers (204). However the product mixtures are complex and very sensitive to conditions. 

We do not know if the vinylic alcohol is actually an intermediate or whether a hydride-71 complex of it rearranges directly to the aldehyde as probably happens in the palladium-catalyzed oxidation of ethylene to acetaldehyde. The formation of 4% 2-methyl-2-phenylpropanal is unexpected. This product must arise from a reversed addition of the phenylpalladium group followed by a hydrogen transfer from the hydroxyl-bearing carbon to the palladium, followed by reductive elimination of a hydridopalladium group. An alkyoxypalladium intermediate has been proposed (39). 

Palladium-catalyzed oxidation of 1,3-dienes in the presence of LiCl and LiOAc produces l-acetoxy-4-chloro-2-alkenes with high selectivity. The reaction is stereospecific and cyclic dienes give an overall cis [1,4] addition (equation 299).644... 

Diacetoxylation of 1,3-dienes. Palladium-catalyzed oxidation of 1,3-cyclo-hcxadicnc with bcnzoquinone (used in catalytic amounts with MnO, as the external oxidant) in acetic acid gives a 1 1 mixture of cis- and //-an.v-1,4-diacctoxy-2-cyclohexene. Addition of LiCI or LiOAc has a profound effect on the stereochemistry. Oxidation in the presence of lithium acetate results in selective tran. -diacetoxylation. whereas addition of lithium chloride results in selective r/.v-diacetoxylation (equation I). ... 

In this synthesis of 1,5-dicaibonyl compounds, 3-butenyl halide is behaving as a madced 3-oxobutyl reagent, and can be used as an equivalent of metiiyl vinyl ketone. These reactirais offer new anellation methods. Also 1,4-addition of the allyl group to enones, followed by oxidatitm. offers a conveiuent synthetic method for 1,5-diketone preparation. Lewis acid promoted Nfichael addition of allylsilane (48) to a,p-unsaturated ketones, followed by the palladium-catalyzed oxidation, affods 1,5-diketones (Scheme 17). 3... 

The Lewis acid promoted addition of allylsilane (48) to nitroalkene (47) gave the unsaturated ketone (49) after hydrolysis of the nitro group. The palladium-catalyzed oxidation affords the 1,4-diketone (50 Scheme 13). °... 

Synthesis of useful 5-oxohexanals can be carried out via the following three reactions (1) 1,2-addition of dlylmagnesium bromide to a, 3-unsaturated aldehydes (61) to give 3-hydroxy-1,5-dienes (62) (2) conversion to 5-hexenals (63) by Ae oxy-Cope rearrangement (3) the palladium-catalyzed oxidation of... 

A new synthetic method for steroids has been developed using a butadiene dimer (66) as a building block and the palladium-catalyzed oxidation as the key reaction.3-Acetoxy-l,7-octadiene (66), prepared by the palladium-catalyzed reaction of butadiene with acetic acid, is hydrolyzed and oxidized to l,7-octadien-3-one (67) in high yield. The enone (67) is a very useful reagent for bisanellation because its termiiud double bond can be regarded as a masked ketone which can be readily unmasked by the palladium catalyst to form the l,S-diketone (68) after Michael addition at the enone moiety of (67 Scheme 20). Thus, the enone (67) is the cheapest and most readily available bisanellation reagent, permitting a simple total synthesis of steroids. 

Cationic palladium-catalyzed addition of arylboronic acids to nitriles for the formation of benzo[h]furans was reported <06OL5987>, an example of which is illustrated in the following scheme. The palladium-catalyzed cross coupling of alkynes with appropriately substituted aryl iodides for the synthesis of substituted dibenzofurans in moderate to excellent yields was also achieved <06JOC5341>. The benzo[fc]furan core of heliannuls G and H were constructed by a palladium-catalyzed Ji-allyl cyclization reaction <06TL7353>. The palladium-catalyzed oxidative activation of arylcyclopropanes was applied to the synthesis of 2-substituted benzo[Z>]furans <06OL5829>. 

The reaction conditions are similar to those employed in the diacetoxylation reaction, with the difference that the halide concentration (usually CI ) has been increased. Thus, palladium-catalyzed oxidation of 1,3-dienes with / -benzoquinone in the presence of lithium chloride and lithium acetate gives l-acetoxy-4-chloroalk-2-enes [78]. For example cyclohexa-1,3-diene and cyclohepta-1,3-diene afforded the corresponding chloroacetates 58a and 58b in good yield and >98% cis selectivity [Eq.(41)]. Cycloocta-1,3-diene gave a 61% yield of acetoxychlorination product (>98% cis), but in this case a 3 1 mixture of 1,4-and 1,2-addition products was formed. A number of substituted cyclic conjugated dienes work well, and, in all cases tried, the reaction proceeds with >97-98% cis selectively [52,78-81]. 

A 1,4-acetoxytrifluoroacetoxylation of 1,3-dienes was obtained in the presence of trifluoroacetic acid and lithium trifluoroacetate [60], For cyclic dienes the relative yield of unsymmetrical 1,4-addition product is high (94-95% or better). For example, palladium-catalyzed oxidation of cyclohexa-1,3-diene under these conditions gave 37 in 67-75% yield [Eq.(37)]. 

Palladium-catalyzed oxidation of 2-(hydroxypropyl)cyclohexa-1,3-diene led to an intramolecular 1,4-addition of an alkoxy group and an acetate (Scheme 8-29) [108]. In the absence of lithium salts a stereoselective tram addition occurs, whereas in the presence of LiCl a l,4-cw addition takes place. 

Palladium-catalyzed oxidation of dienamides 88 in acetone in the presence of acetic acid gives oxyamination products in stereoselective reactions (Scheme 8-33) [113]. Depending on the reaction conditions, it is possible to obtain trans- or cis-1,4-oxyamination by choice. As with the other palladium(II)-catalyzed 1,4-additions, CI (from LiCl) is used as a... 

In this reaction the first addition product was isolated, in catalytic reactions this is not the case and in these reactions the first (cr-alkyl)palladium complex formed from the nucleophilic addition reacts further. For example, in the palladium-catalyzed oxidation of 1,5-cyclooctadiene with Pb(OAc)4 in acetic acid the corresponding diacetate 6 was obtained in 76% yield together with some chloroacetate (equation Adduct 7 is the... 

The palladium-mediated allylation proceeds via an initial oxidative addition of an allylic substrate to Pd(0). The resultant TC-allylpalladium(II) complex A is electrophilic and reacts with carbon nucleophiles generating the Pd(0) complex B, which undergoes ligand exchange to release the product and restart the cycle for palladium. With substituted allylic compounds, the palladium-catalyzed nucleophilic addition usually occurs at the less substituted side. 

Ito and his coworkers have reported that palladium-catalyzed oxidative coupling reactions of Grignard reagents in the presence of V-substituted isocyanide dichloride afford diynes (equation 17). Isocyanide dichloride may serve as a reoxidant of the palladium catalyst in this sequence via a catalytic cycie. In addition Kiji and his coworkers have described the oxidative coupling of phenylacetylene by a Pd-Cu catalyst in the presence of 4-iodo-(3//) phenothiazin-3-one. ... 

Heterocycles - Aromatic substitution via N-oxides has been reviewed.51 Palladium catalyzed intramolecular addition of amines to olefins has resulted in new syntheses of indoles52-3 and isoquinuclidines.53... 

In 2003, Stoltz at CalTech described a palladium-catalyzed oxidative Wacker cyclization of o-allylphenols such as 55 in nonpolar organic solvents with molecular oxygen to afford dihydrobenzofurans such as 56.44 Interestingly, when (-)-sparteine was used in place of pyridine, dihydrobenzofuran 56 was produced asymmetrically. The ee reached 90% when Ca(OH)2 was added as an additive. Stoltz considered it a stepping stone to asymmetric aerobic cyclizations. In 2004, Mufiiz carried out aerobic, intramolecular Wacker-type cyclization reactions similar to 55—>56 using palladium-carbene catalysts.45 Hiyashi et al. investigated the stereochemistry at the oxypalladation step in the Wacker-type oxidative cyclization of an o-allylphenol. Like o-allylphenol, o-allylbenzoic acid 57 underwent the Wacker-type oxidative cyclization to afford lactone 58.47... 

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