Pd-catalyzed reaction

Of course. Pd is a noble metal and expensive, but it is much less expensive than Rh, Pt. and Os. Also, the toxicity of Pd has posed no problem so far. The fact that a number of industrial processes (more than ten at least) based on Pd-catalyzed reactions have been developed and are now operated reflects these advantages of using Pd catalysts commercially[l]. 

The wM-diacetate 363 can be transformed into either enantiomer of the 4-substituted 2-cyclohexen-l-ol 364 via the enzymatic hydrolysis. By changing the relative reactivity of the allylic leaving groups (acetate and the more reactive carbonate), either enantiomer of 4-substituted cyclohexenyl acetate is accessible by choice. Then the enantioselective synthesis of (7 )- and (S)-5-substituted 1,3-cyclohexadienes 365 and 367 can be achieved. The Pd(II)-cat-alyzed acetoxylactonization of the diene acids affords the lactones 366 and 368 of different stereochemistry[310]. The tropane alkaloid skeletons 370 and 371 have been constructed based on this chemoselective Pd-catalyzed reactions of 6-benzyloxy-l,3-cycloheptadiene (369)[311]. 

Chlorobenzene reacts with alkenes with bimetallic catalyses of Ni and Pd. Chlorobenzene is converted in situ into iodobenzene (14) by the Ni-cataiyzed reaction of Nal at 140 "C. NiBr2, rather than the Ni(0) complex, is found to be a good catalyst. Then the Pd-catalyzed reaction of the iodobenzene with acrylate takes place) 15]. 

The benzene derivative 409 is synthesized by the Pd-catalyzed reaction of the haloenyne 407 with alkynes. The intramolecular insertion of the internal alkyne, followed by the intermolecular coupling of the terminal alkyne using Pd(OAc)2, Ph3P, and Cul, affords the dienyne system 408, which cyclizes to the aromatic ring 409[281]. A similar cyclization of 410 with the terminal alkyne 411 to form benzene derivatives 412 and 413 without using Cul is explained by the successive intermolecular and intramolecuar insertions of the two triple bonds and the double bond[282]. The angularly bisannulated benzene derivative 415 is formed in one step by a totally intramolecular version of polycycli-zation of bromoenediyne 414[283,284],... 

Organolithium and -magnesium compounds. Compared with extensive studies carried out on the Ni-catalyzed transmetallation reaction of Grignard reagents[43I,432], few examples of the Pd-catalyzed reactions of Mg are... 

The arylation of the i-tributyistannyl glycai 717 offers a synthetic route to chaetiacandin[585,586]. The Pd-catalyzed reactions of the 3-stannylcyclobute-nedione 718 with iodobenzene, and benzoyl chloride[S87], and alkenylation with alkenyl(phenyl)iodonium triflates proceed smoothly by the co-catalysis by Cul[588,589],... 

Acyl halides react with organometallic reagents without catalysts, but sometimes the Pd-catalyzed reactions give higher yields and selectivity than the Lincatalyzed reactions. Acyl halides react with Pd(0) to form the acylpalladium complexes 846, which undergo facile transmetallation. 

The Pd-catalyzed hydrogenoiysis of acyl chlorides with hydrogen to give aldehydes is called the Rosenmund reduction. Rosenmund reduction catalyzed by supported Pd is explained by the formation of an acylpalladium complex and its hydrogenolysis[744]. Aldehydes can be obtained using other hydrides. For example, the Pd-catalyzed reaction of acyl halides with tin hydride gives aldehydes[745]. This is the tin Form of Rosenmund reduction. Aldehydes are i ormed by the reaction of the thio esters 873 with hydrosilanes[746,747]. 

Based on the above-mentioned stereochemistry of the allylation reactions, nucleophiles have been classified into Nu (overall retention group) and Nu (overall inversion group) by the following experiments with the cyclic exo- and ent/n-acetales 12 and 13[25], No Pd-catalyzed reaction takes place with the exo-allylic acetate 12, because attack of Pd(0) from the rear side to form Tr-allyl-palladium is sterically difficult. On the other hand, smooth 7r-allylpalladium complex formation should take place with the endo-sWyWc acetate 13. The Nu -type nucleophiles must attack the 7r-allylic ligand from the endo side 14, namely tram to the exo-oriented Pd, but this is difficult. On the other hand, the attack of the Nu -type nucleophiles is directed to the Pd. and subsequent reductive elimination affords the exo products 15. Thus the allylation reaction of 13 takes place with the Nu nucleophiles (PhZnCl, formate, indenide anion) and no reaction with Nu nucleophiles (malonate. secondary amines, LiP(S)Ph2, cyclopentadienide anion). 

Since allylation with allylic carbonates proceeds under mild neutral conditions, neutral allylation has a wide application to alkylation of labile compounds which are sensitive to acids or bases. As a typical example, successful C-allylation of the rather sensitive molecule of ascorbic acid (225) to give 226 is possible only with allyl carbonate[l 37]. Similarly, Meldrum s acid is allylated smoothly[138]. Pd-catalyzed reaction of carbon nucleophiles with isopropyl 2-methylene-3,5-dioxahexylcarbomite (227)[I39] followed by hydrolysis is a good method for acetonylation of carbon nucleophiles. 

Allylic metal compounds useful for further transformations can be prepared by Pd-catalyzed reactions of allylic compounds with bimetallic reagents. By this transformation, umpolung of nucleophilic 7r-allylpalladium complexes to electrophilic allylmetal species can be accomplished. Transfer of an allyl moiety from Pd to Sn is a typical umpolung. 

The protected nucleoside-3-phosphoramidite monomer units such as 671 are used in the solid-phase oligonucleotide synthesis. In the 60mer synthesis, 104 allylic protective groups are removed in almost 100% overall yield by the single Pd-catalyze reaction with formic acid and BuNH2[432], N,(9-protection of uridine derivatives was carried out under pha.se-transfer conditions[433]. 

Pd-catalyzed reactions of sulfur-containing nucleophiles, SO2, CSj and S, were summarized in a review[101]. When 3-sulfolene (109) is treated with butadiene at I00"C, cis- and /ra j-2,5-divinyisulfolanes (110) are obtained. Under these conditions. 3-sulfolene (109) decomposes to butadiene and SOj, which react to give divinylsulfolane (I10)[I02]. Divinylsulfolane (110) can be obtained directly by the reaction of SO2 with butadiene[103]. 

Propargylic (or 2-alkynyl) compounds are derivatives of alkynes. However, Pd-catalyzed reactions of propargylic derivatives, particularly esters and halides, are very different mechanistically from those of simple alkynes, except in a few cases. Therefore, the reactions of propargylic esters and halides are treated in this section separately from those of other alkynes. However, some reactions of propargylic alcohols, which behave similarly to simple alkynes, are treated in Section 6. 

Organoboranes react with propargylic carbonates. Usually, addition of a base is essential for the Pd-catalyzed reactions of organoboranes, but the reaction with propargylic carbonates proceeds without addition of the base, because methoxide is generated in situ from carbonates. For example, the 1,2,4-triene 80 is prepared by the reaction of alkenylborane under neutral conditions[36]. 

Aikynes insert into the silacyclobutane 168 to form the silacyclohe.xene 169[93]. Also, the silacyclopropene 170 is expanded to the silacyclopentadiene 171 by the insertion of an alkyne[94]. The insertion product 173 was obtained by the Pd-catalyzed reaction of the neopentylidenesilirane 172 with acety-lene[95]. 

Stereoselective and chemoselective semihydrogenation of the internal alkyne 208 to the ew-alkene 210 is achieved by the Pd-catalyzed reaction of some hydride sources. Tetramethyldihydrosiloxane (TMDHS) (209) i.s used in the presence of AcOH[116]. (EtO)3SiH in aqueous THF is also effective for the reduction of alkynes to di-alkenes[l 17], Semihydrogenation to the d.v-alkene 211 is possible also with triethylammonium formate with Pd on carbon[118]. Good yields and high cis selectivity are obtained by catalysis with Pd2fdba)3-Bu3P[119],... 

The chemoselective desilylation of one of the two different silyi enoi ethers in 10 to give the monosilyl enol ether II is realized by the Pd-catalyzed reaction of Bu3SnF. The chemoselectivity is controlled by steric congestion and the relative amount of the reagent[7,8]. An interesting transformation of the 6-alkoxy-2,3-dihydro-6//-pyran-3-one 12 into the cyclopentenone derivative 13 proceeds smoothly with catalysis by Pd(OAc)2 (10 mol%)[9]. 

The skeletal rearrangement of various strained cyclic compounds is carried out with a catalytic amount of soluble complexes of PdCl2. Namely, the rearrangements of bulvalene (67) to bicyclo[4.2.2]deca-2,4,7,9-tetraene (68)[54], cubane (69) to cuneane (70)[55], hexamethyl Dewar benzene (71) to hexa-methylbenzene (72)[56], and 3-oxaquadricyclanes[57] and quadricyclane (73) to norbornadiene[58-60] take place mostly at room temperature. Reaction of iodocubane (74) with a terminal alkyne catalyzed by Pd(0) and CuBr unexpectedly affords an alkynylcyclooctatetraene 75, without giving the desired cubylalkyne 76. Probably the rearrangement is a Pd-catalyzed reaction[61]. 

Syntheses of natural O- and N-heterocycles via stereocontrolled Pd-catalyzed reactions 99PAC1065. 

With regard to the mechanism of these Pd°-catalyzed reactions, little is known in addition to what is shown in Scheme 10-62. In our opinion, the much higher yields with diazonium tetrafluoroborates compared with the chlorides and bromides, and the low yields and diazo tar formation in the one-pot method using arylamines and tert-butyl nitrites (Kikukawa et al., 1981 a) indicate a heterolytic mechanism for reactions under optimal conditions. The arylpalladium compound is probably a tetra-fluoroborate salt of the cation Ar-Pd+, which dissociates into Ar+ +Pd° before or after addition to the alkene. An aryldiazenido complex of Pd(PPh3)3 (10.25) was obtained together with its dediazoniation product, the corresponding arylpalladium complex 10.26, in the reaction of Scheme 10-64 by Yamashita et al. (1980). Aryldiazenido complexes with compounds of transition metals other than Pd are discussed in the context of metal complexes with diazo compounds (Zollinger, 1995, Sec. 10.1). 

Brick et al. have studied this bromination in more detail and showed that the extent of the bromination can be controlled by changing the ratio of the reagents. The first substitution was found to be in the para position but subsequent intramolecular rearrangements allowed the formation of 2-5-dibrominated species. Brick et al. also reported the functionalization of such species using Pd-catalyzed reactions such as Heck and Suzuki couplings to give fully substituted p-stilbenes, p-biphenyls, diarylamines, and methylcinnamates. Hydrogenation of... 

Scheme 7-17 A possible path of Pd-catalyzed reaction of (ArS)2 with 73...

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