Oxypalladation catalytic

The intramolecular oxidative earbonylation has wide synthetie applieation. The 7-lactone 247 is prepared by intramolecular oxycarbonylation of the alke-nediol 244 with a stoichiometric amount of Pd(OAc)2 under atmospheric pres-sure[223]. The intermediate 245 is formed by oxypalladation, and subsequent CO insertion gives the acylpalladium 246. The oxycarbonylation of alkenols and alkanediols can be carried out with a catalytic amount of PdCl2 and a stoichiometric amount of CuCb, and has been applied to the synthesis of frenolicin(224] and frendicin B (249) from 248[225]. The carbonylation of the 4-penten-l,3-diol 250, catalyzed by PdCl2 and CuCl2, afforded in the c -3-hydroxytetrahydrofuran-2-aeetie acid lactone 251[226J. The cyclic acetal 253 is prepared from the dienone 252 in the presence of trimethyl orthoformate as an accepter of water formed by the oxidative reaction[227]. 

The phenolic oxygen on 2-allyl-4-bromophenol (7) readily underwent oxypalladation using a catalytic amount of PdCl2 and three equivalents of Cu(OAc)2, to give the corresponding benzofuran 8. This process, akin to the Wacker oxidation, was catalytic in terms of palladium, and Cu(OAc)2 served as oxidant [17]. Benzofuran 10, a key intermediate in Kishi s total synthesis of aklavinone [18], was synthesized via the oxidative cyclization of phenol 9 using stoichiometric amounts of a Pd(II) salt. 

A phenolic oxygen participates in facile oxypalladation. 2-Allylphenol (55) undergoes clean cyclization to 2H-l-benzopyran (56) in DMSO under air with a catalytic amount of Pd(OAc)2 without a reoxidant. 2-Methylbenzofuran (57) is obtained when PdCl2 is used [50]. But different chemoselectivity with the Pd(II) salts was also reported [51]. Catalytic asymmetric cyclization of the tetrasubstituted 2-allylic phenol 58 using the binaphthyl-type chiral ligand 60, called (.S, .S )-ip-borax, afforded the furan 59 with 96% ee. Use of Pd(CF3 002)2 as a catalyst is essential in the presence of benzoquinone [52]. Formation of the benzofuran 62 from 61 has been utilized in the synthesis of aklavinione [53]. The intramolecular reaction of 2-hydroxychalcone (63) produces the flavone 64 [54]. 

An example of catalytic oxypalladation is the rearrangement of allylic acetates with Pd ll). The reaction starts with oxypalladation of the alkene and it is the acetate already present in the molecule that provides the nucleophile to attack... 

Cyclic ethers and amines can be formed if the nucleophile is an intramolecular alcohol or amine. Stoichiometric palladium can be avoided by using benzoquinone as the stoichiometric oxidant with a catalytic amount of palladium. In this example intramolecular oxypalladation of a diene is followed by attack of an external nucleophile on a TC-allyl complex. 

In the presence of CO, terminal alkenes are oxidized by PdCl2 to RCH(C1)CH2C0C1. When the reaction is made catalytic in palladium by the addition of CuCl2 and oxygen, and carried out in alcohols, the products are a, /3-unsaturated esters, /3-alkoxy esters, and, under some conditions, succinate derivatives (equation 87). Two mechanisms are possible for this reaction. In the first, an oxypalladation can produce a Pd-CH2-CH2-X species, which can undergo CO insertion into the Pd-C bond. Alternatively, an XCOPd species can form and add across the double bond. Loss of Pd-H can generate the a, /3-unsaturated ester, or a second carbonylation step can lead to succinate derivatives. 

Consider the first oxidative cyclization shown to produce A. It was proposed originally that the cyclization proceeded through if-allyl-Pd intermediate B. Treatment of C, however, which was predicted to form B under the same reaction conditions, led to A in less than 5% yield, even after 21 hours of reaction time. The researchers involved were forced to come up with another mechanism. Propose an alternate catalytic pathway that involves complexation of the phenolic oxygen and side chain C=C bond to Pd and then oxypalladation of the C=C bond.213... 

Pd(OAc)2 can catalyze the reaction of 2,3-allenoic acids with non-allylic alkenyl bromides with a terminal C=C bond leading to P-alkenyl butenolides 61 and 62 (Scheme 29). The reaction proceeded via oxypalladation-carbopal-ladation, repeated P-dehydropalladation/hydropalladation-dehalopalladation, in which Pd(II) is the catalytically active species [21]. 

A phenolic oxygen participates in facile oxypalladation [16], Different chemos-electivity is observed depending on the catalytic species. The 2H-l-benzopyran 66 was formed cleanly from 2-allylphenol (65) by endo cyclization with Pd2(dba)3 or... 

The unsaturated hydroxy carboxylic acid 152 was converted to the dilactone 153 via domino oxypalladation and carbonylation [63]. The y-lactone 156 was prepared by intramolecular oxycarbonylation of the alkenediol 154. The intermediate 155 is formed by the oxypalladation, and subsequent intramolecular carbonylation affords the lactone 156. The reaction was applied to the synthesis of tetrono-mycin [64]. The oxycarbonylations of alkenol and alkanediol can be carried out with a catalytic amount of PdCl2 and a stoichiometric amount of CuCl2, and have been applied to syntheses of a number of natural products. 

Intramolecular oxypalladation of 5,6-dienoic acid 252 is followed by acrolein insertion to generate 254, which undergoes protonolysis to produce the aldehyde 253 without giving elimination product as a Heck-type reaction. The reaction proceeds with a catalytic amount of Pd(OAc>2 in the presence of LiBr, which plays an important role in inhibiting j6-H elimination in 254 [108]. Reaction of 252 in the presence of Pd(OAc>2, Cu(OAc), LiBr and O2 in MeCN provided alkenyl bromide 255 [109]. 

A similar experiment with an unsaturated alcohol reported by Stoltz also implies that syn oxypalladation occurs. Again, the observation of deuterium in the product implies that the alkoxyalkylpalladium intermediate contains the palladium cis to the alkoxo group and trans to the deuterium label. The stereochemical outcome of catalytic cyclizations reported by Wolfe also imply that cis oxypalladation occurs during certain transformations, as shown in Equation 9.82. 

In catalytic reactions involving Pd(II) salts, carboxypalladation yields an alkylpal-ladium species that can often undergo (3-H elimination instead of protonolysis. Subsequently, Stoltz and coworkers demonstrated that Wacker-type processes can also afford lactones under oxidative conditions (Scheme 2.35). The proposed mechanism involves Pd(II) coordination to the alkene, followed by oxypalladation and (3-H elimination. After elimination of HX to form Pd(0), aerobic oxidation is required to regenerate a Pd(II) species. The net result is olefin transposition to an adjacent position [80]. 

From hydroxyalkenes derived from (/ )-(-)- or (5)-(+)-phenethyIamme and/or (5 )-(+)-lactic acid or (li , 25)-(-)-ephedrine, optically active tetrahydro-l,4-oxazines have been synthesized by using either MeOH or H2O as the nucleophile (Scheme The diastereoselectivities observed are high. In this case, the use of excess amounts of copper salts makes the reaction catalytic even in the absence of Oj. Interception of the Pd—C bond in oxypalladation adduct by chloride ion yields 2-chloromethyl-l,4-oxazines as shown in Scheme 30. ... 

As shown in Scheme 13.22, a chiral catalyst was generated from Pd(TFA)2 and the enantiomerically pure ligand 144. Alkene 143 coordinated enantiofacially through its double bond to the chiral catalyst to give the intermediate 145, which reacted further by oxypalladation to produce 146 with the formation of a chroman framework and construction of the stereogenic center. The subsequent Heck reaction of palladium species 146 with acrylate formed the intermediate 147, which led to the final product 148 and Pd° by p-hydride elimination. It was necessary to reoxidize Pd° to Pd for the catalytic cycle, which was achieved by the addition of p-benzoquinone to the reaction mixture. The synthesis of a-tocopherol was finally completed by subsequent transformations of the side chain within 148. 

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