Hard carbon nucleophiles

Formation of a Tr-allylpalladium complex 29 takes place by the oxidative addition of allylic compounds, typically allylic esters, to Pd(0). The rr-allylpal-ladium complex is a resonance form of ir-allylpalladium and a coordinated tt-bond. TT-Allylpalladium complex formation involves inversion of stereochemistry, and the attack of the soft carbon nucleophile on the 7r-allylpalladium complex is also inversion, resulting in overall retention of the stereochemistry. On the other hand, the attack of hard carbon nucleophiles is retention, and hence Overall inversion takes place by the reaction of the hard carbon nucleophiles. 

The phenylation of styrene with phenyl Grignard reagents as a hard carbon nucleophile proceeds in 75% yield in the presence of PdCl2, LiCl, and K2CO3 at room temperature to give stilbene (207). Selection of the solvent is crucial and the best results are obtained in MeCN. The reaction can be made catalytic by the use of CuCl2[197]. Methyllithium reacts with styrene in the presence of Pd(acac)2 or Pd(OAc)2 to give /3-methylstyrene (208) in 90% yield[198]. 

Hard carbon nucleophiles of organometallic compounds react with 7r-allyl-palladium complexes. A steroidal side-chain is introduced regio- and stereo-selectively by the reaction of the steroidal 7T-allylpalladium complex 319 with the alkenylzirconium compound 320[283]. 

In addition, a catalytic version of Tt-allylpalladium chemistry has been devel-oped[6,7]. Formation of the Tr-allylpalladium complexes by the oxidative addition of various allylic compounds to Pd(0) and subsequent reaction of the complex with soft carbon nucleophiles are the basis of catalytic allylation. After the reaction, Pd(0) is reformed, and undergoes oxidative addition to the allylic compounds again, making the reaction catalytic.-In addition to the soft carbon nucleophiles, hard carbon nucleophiles of organometallic compounds of main group metals are allylated with 7r-allylpalladium complexes. The reaction proceeds via transmetallation. These catalytic reactions are treated in this chapter. 

The stereochemistry of the Pd-catalyzed allylation of nucleophiles has been studied extensively[5,l8-20]. In the first step, 7r-allylpalladium complex formation by the attack of Pd(0) on an allylic part proceeds by inversion (anti attack). Then subsequent reaction of soft carbon nucleophiles, N- and 0-nucleophiles proceeds by inversion to give 1. Thus overall retention is observed. On the other hand, the reaction of hard carbon nucleophiles of organometallic compounds proceeds via transmetallation, which affords 2 by retention, and reductive elimination affords the final product 3. Thus the overall inversion is observed in this case[21,22]. 

Cross-Couplinf of Allylic Groups with Hard Carbon Nucleophiles... 

Dienes and allylarcncs can be prepared by the Pd-catalyzcd coupling of allylic compounds with hard carbon nucleophiles derived from alkenyl and aryl compounds of main group metals. Allylic compounds with various leaving groups can be used. Some of them are unreactive with soft nucleophiles, but... 

The reaction of 2,3-butadienyl acetate (843) with soft carbon nucleophiles such as dimethyl malonate gives dimethyl 2,3-butadienylmalonate (844)[520]. On the other hand, the reaction of the 2,3-butadienyl phosphate 845 with hard carbon nucleophiles such as Mg and Zn reagents affords the 2-allcyl-1,3-butadiene 846[520,521]. The 3-methoxy-1,3-butadiene 848 is obtained by the reaction of the 2-methoxy-2,3-butadienyl carbonate 847 with organozinc reagent. 

Among several propargylic derivatives, the propargylic carbonates 3 were found to be the most reactive and they have been used most extensively because of their high reactivity[2,2a]. The allenylpalladium methoxide 4, formed as an intermediate in catalytic reactions of the methyl propargylic carbonate 3, undergoes two types of transformations. One is substitution of cr-bonded Pd. which proceeds by either insertion or transmetallation. The insertion of an alkene, for example, into the Pd—C cr-bond and elimination of/i-hydrogen affords the allenyl compound 5 (1.2,4-triene). Alkene and CO insertions are typical. The substitution of Pd methoxide with hard carbon nucleophiles or terminal alkynes in the presence of Cul takes place via transmetallation to yield the allenyl compound 6. By these reactions, various allenyl derivatives can be prepared. 

Other hard carbon nucleophiles, such as organoaluminium [31] or organoboron [32, 33] reagents, are also applicable to the Pd-catalyzed SN2 substitution of pro-... 

As shown in the previous sections, a (cr-allenyl)palladium species, which is formed from a propargyl electrophile and a Pd(0) catalyst, reacts with a hard carbon nucleophile in a manner analogous to the Pd-catalyzed cross-coupling reaction to give a substituted allene. The results indicate that the reactivity of the (cj-allenyl)palladium species is similar to that of an alkenylpalladium intermediate. Indeed, it was found that the (cr-allenyl)palladium species reacted with olefins to give vinylallenes, a reaction process that is similar to that of the Heck reaction of alkenyl halides [54]. 

Hard carbon nucleophiles that do not contain stabilizing electron-withdrawing substituents have been shown to react with allylic carbonates only recently in the... 

The addition of Grignards and organolithium reagents proceeds by attack at the metal center in ir-allylpalladium complexes. The regiochemical selectivity exhibited by these hard carbon nucleophiles with ir-allyl complexes substituted at the termini with alkyl or aryl groups is comparable to the soft carbon nucleophiles (ligand attack) in most cases, with addition occurring predominantly at the less substituted terminus (equations 248 and 249).1591387... 

The reactions of type II proceed by transmetallation of the complex 5. The transmetallation of 5 with hard carbon nucleophiles M R (M = main group metals) such as Grignard reagents and metal hydrides MH generates 8. Subsequent reductive elimination gives rise to an allene derivative as the final product. Coupling reactions of terminal alkynes in the presence of Cul belong to Type II. 

The reactions of Type II proceed by transmetallation of the complex 8, Hard carbon nucleophiles MR (M = Main group metal), such as Grignard reagents and metal hydrides... 

Similarly palladium-catalyzed nucleophilic allylic coupling of 1-vinylcyclopropan-l-ol and its derivatives with stabilized (soft) and nonstabilized (hard) carbon nucleophiles occurred regioselectively without ring opening of the three-membered ring to give, for example, 9. ... 

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