Alkenes Pd -catalyzed

Facile metallation of allenes offers convenient synthetic methods of functionalized alkenes. Pd-catalyzed cis hydrostaimation of allenes proceeds smoothly via either hydropalladation or staimylpalladation of 1,2-dienes with H-Pd-SnBu3 to produce allylstaimanes 122 or vinylstaimane 123 [38]. 

It is possible to prepare 1-acetoxy-4-chloro-2-alkenes from conjugated dienes with high selectivity. In the presence of stoichiometric amounts of LiOAc and LiCl, l-acetoxy-4-chloro-2-hutene (358) is obtained from butadiene[307], and cw-l-acetoxy-4-chloro-2-cyclohexene (360) is obtained from 1.3-cyclohexa-diene with 99% selectivity[308]. Neither the 1.4-dichloride nor 1.4-diacetate is formed. Good stereocontrol is also observed with acyclic diene.s[309]. The chloride and acetoxy groups have different reactivities. The Pd-catalyzed selective displacement of the chloride in 358 with diethylamine gives 359 without attacking allylic acetate, and the chloride in 360 is displaced with malonate with retention of the stereochemistry to give 361, while the uncatalyzed reaction affords the inversion product 362. 

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]. 

Total syntheses of tazettine and 6a-epi-pretazettine have been carried out by application of the Pd-catalyzed cydization of 169, in which a single pentacyclic product 170 was obtained, establishing a preference for an eclipsed orientation of the Pd—C (7-bond and alkene 7r-bond in the key intramolecular insertion step[l40]. 

A interesting and useful reaetion is the intramolecular polycyclization reaction of polyalkenes by tandem or domino insertions of alkenes to give polycyclic compounds[l 38]. In the tandem cyclization. an intermediate in many cases is a neopentylpalladium formed by the insertion of 1,1-disubstituted alkenes, which has no possibility of /3-elimination. The key step in the total synthesis of scopadulcic acid is the Pd-catalyzed construction of the tricyclic system 202 containing the bicyclo[3.2. Ijoctane substructure. The single tricyclic product 202 was obtained in 82% yield from 201 [20,164). The benzyl chloride 203 undergoes oxidative addition and alkene insertion. Formation of the spiro compound 204 by the intramolecular double insertion of alkenes is an exam-ple[165]. 

Intramolecular reaction can be used for polycyclization reaction[275]. In the so-called Pd-catalyzed cascade carbopalladation of the polyalkenyne 392, the first step is the oxidative addition to alkenyl iodide. Then the intramolecular alkyne insertion takes place twice, followed by the alkene insertion twice. The last step is the elimination of/3-hydrogen. In this way, the steroid skeleton 393 is constructed from the linear diynetriene 392(276]. 

The thioboration of terminal alkynes with 9-(alkylthio)-9-borabicyclo[3.3.1]-nonanes (9-RS-9-BBN) proceeds regio- and stereoselectively by catalysis of Pd(Ph,P)4 to produce the 9-[(Z)-2-(alkylthio)-l-alkeny)]-9-BBN derivative 667 in high yields. The protonation of the product 667 with MeOH affords the Markownikov adduct 668 of thiol to 1-alkyne. One-pot synthesis of alkenyl sulfide derivatives 669 via the Pd-catalyzed thioboration-cross-coupling sequence is also possible. Another preparative method for alkenyl sulfides is the Pd-catalyzed cross-coupling of 9-alkyl-9-BBN with l-bromo-l-phe-nylthioethene or 2-bromo-l-phenylthio-l-alkene[534]. 

The Pd-catalyzed hydrogenolysis of allylic compounds by various hydrides gives alkenes. From terminal allylic compounds, either 1-alkenes or 2-alkenes are formed depending on the hydride sources [360a]. 

As a further application of the reaction, the conversion of an endocyclic double bond to an c.xo-methylene is possible[382]. The epoxidation of an cWo-alkene followed by diethylaluminum amide-mediated isomerization affords the allylic alcohol 583 with an exo double bond[383]. The hydroxy group is eliminated selectively by Pd-catalyzed hydrogenolysis after converting it into allylic formate, yielding the c.ro-methylene compound 584. The conversion of carvone (585) into l,3-disiloxy-4-methylenecyclohexane (586) is an example[382]. 

The Pd-catalyzed hydrogenolysis of vinyloxiranes with formate affords homoallyl alcohols, rather than allylic alcohols regioselectively. The reaction is stereospecific and proceeds by inversion of the stereochemistry of the C—O bond[394,395]. The stereochemistry of the products is controlled by the geometry of the alkene group in vinyloxiranes. The stereoselective formation of stereoisomers of the syn hydroxy group in 630 and the ami in 632 from the ( )-epoxide 629 and the (Z)-epoxide 631 respectively is an example. 

Similarly to alkenes. alkynes also insert. In the reaction of 775 carried out under a CO atmosphere in AcOH, sequential insertions of alkyne, CO. alkene. and CO take place in this order, yielding the keto ester 776[483]. However, the same reaction carried out in THF in the presence of LiCl affords the ketone 777, but not the keto ester[484]. The tricyclic terpenoid hirsutene (779) has been synthesized via the Pd-catalyzed metallo-ene carbonylation reaction of 778 with 85% diastereoselectivity as the key reaction[485], Kainic acid and allo-kainic acid (783) have been synthesized by the intramolecular insertion ol an alkene in 780, followed by carbonylation to give 781 and 782[486],... 

The reaction of the allylic acetate with a diene system 784 affords the poly-fused ring system 785 by three repeated alkene insertions[487]. An even more strained molecule of the [5.5.5.5] fenestrane 788 has been constructed by a one-pot reaction in a satisfactory yield by the Pd-catalyzed carbonylation-cycliza-tion of 786 without undergoing elimination of /3-hydrogen in the cr-alkylpalla-dium intermediate 787 owing to unfavorable stereochemistry for syn elimination[488]. 

Diaryl disulfides and diselenides add to alkynes to afford the (Z)-l, 2-bis(ar-ylthio)alkenes 193 and (Z)-l,2-bis(arylseleno)alkenes 194. Under CO pressure, carbonylative addition takes place to give thio esters and the selenoketones 195[I07], The selenoketones are converted into the /J-seleno-a, 3-unsaturated aldehydes 196 by Pd-catalyzed hydrogenolysis with HSnBu3[108,109],... 

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],... 

Addition of nucleophiles to both activated and unactivated alkenes is catalyzed by Pd(II). Addition of alcohols or AcOH to alkenes bearing EWGs is catalyzed by PdCl2(PhCN)2 to give the corresponding ethers and esters. The addition of an alcohol to the cyclic acetal of acrolein 82 to give the ether 83 is also possible with the same catalyst[64]. Amines add to the vinylic ether 84 to give 85, but not to simple alkenes[65]. 

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). 

The Pd-catalyzed coupling reaction of aryl-alkenyl halides widi alkenes in the... 

A chelation-assisted Pd-catalyzed Cope rearrangement was proposed in the reaction of phenanthroline to generate isoquinolinone derivatives (Eq. 12.78).177 The use of aqueous media and ligands enables a double-Heck reaction on a substrate favoring alkene insertion over (J>-hydride elimination. 

Transition metal-catalyzed transformations are of major importance in synthetic organic chemistry [1], This reflects also the increasing number of domino processes starting with such a reaction. In particular, Pd-catalyzed domino transformations have seen an astounding development over the past years with the Heck reaction [2] - the Pd-catalyzed transformation of aryl halides or triflates as well as of alkenyl halides or triflates with alkenes or alkynes - being used most often. This has been combined with another Heck reaction or a cross-coupling reaction [3] such as Suzuki, Stille, and Sonogashira reactions. Moreover, several examples have been published with a Tsuji-Trost reaction [lb, 4], a carbonylation, a pericyclic or an aldol reaction as the second step. 

A typical second step after the insertion of CO into aryl or alkenyl-Pd(II) compounds is the addition to alkenes [148]. However, allenes can also be used (as shown in the following examples) where a it-allyl-r 3-Pd-complex is formed as an intermediate which undergoes a nucleophilic substitution. Thus, Alper and coworkers [148], as well as Grigg and coworkers [149], described a Pd-catalyzed transformation of o-iodophenols and o-iodoanilines with allenes in the presence of CO. Reaction of 6/1-310 or 6/1-311 with 6/1-312 in the presence of Pd° under a CO atmosphere (1 atm) led to the chromanones 6/1-314 and quinolones 6/1-315, respectively, via the Jt-allyl-r 3-Pd-complex 6/1-313 (Scheme 6/1.82). The enones obtained can be transformed by a Michael addition with amines, followed by reduction to give y-amino alcohols. Quinolones and chromanones are of interest due to their pronounced biological activity as antibacterials [150], antifungals [151] and neurotrophic factors [152]. 

Hydroxycarbonylation and alkoxycarbonylation of alkenes catalyzed by metal catalyst have been studied for the synthesis of acids, esters, and related derivatives. Palladium systems in particular have been popular and their use in hydroxycarbonylation and alkoxycarbonylation reactions has been reviewed.625,626 The catalysts were mainly designed for the carbonylation of alkenes in the presence of alcohols in order to prepare carboxylic esters, but they also work well for synthesizing carboxylic acids or anhydrides.137 627 They have also been used as catalysts in many other carbonyl-based processes that are of interest to industry. The hydroxycarbonylation of butadiene, the dicarboxylation of alkenes, the carbonylation of alkenes, the carbonylation of benzyl- and aryl-halide compounds, and oxidative carbonylations have been reviewed.6 8 The Pd-catalyzed hydroxycarbonylation of alkenes has attracted considerable interest in recent years as a way of obtaining carboxylic acids. In general, in acidic media, palladium salts in the presence of mono- or bidentate phosphines afford a mixture of linear and branched acids (see Scheme 9). 

---