Transmetallation position-selective

Starting with a diene monoxide, we may generate a zwitterionic alkoxide moiety that should also activate a C—Si bond (left-hand side of Scheme 10-11). In fact, diene monoxides were found to couple with alkenyl(fluoro)dimethysilanes and aryl(difluoro)ethylsilanes [Eq.(38)]. Again the regiocontrol of the coupling was hoped to be based on the assumed position-selective transmetallation, but the experimental results show that the control was only partly successful, probably due to the fast configurational equilibrium of the intermediate 77 -allylpalladium species. 

Terminal trimethylsilylacetylenes are deprotonated at the propargylic position by using sBuLi to yield a lithiated species which undergoes transmetallation with ZnBr2 to afford the allenylzinc reagent (Eq. 9.125) [99]. Additions to a-alkoxyalde-hydes are relatively unselective (Table 9.48), whereas additions to a-alkoxy imines are highly anti selective (Eq. 9.126). 

To elucidate the reaction pathway, deuterium-labeled allenyl pinacol boronate 10 was prepared, and the addition reaction with hydrazonoester 6 was conducted in the presence of Bi(OH)3 and Cu(OH)2 (Scheme 4). In both Bi- and Cu-catalyzed cases, the reactions proceeded smoothly (in quantitative yields in both cases). In the Bi(OH)3-catalyzed reaction, a major product was allenyl compound 11, in which the internal position was deuterized. It was assumed that a propargyl bismuth was formed via transmetalation from boron to bismuth, followed by addition to hydrazonoester via y-addition to afford allenyl compound 11. Thus, two y-additions could selectively provide a-addition products [75, 76, 105, 106]. It was confirmed that isomerization of 10 did not occur. Recently, we reported Ag20-catalyzed anti-selective a-addition of a-substituted allyltributyltin with aldehydes in aqueous media [107], On the other hand, in the Cu(OH)2-catalyzed reaction, a major product was propargyl compound 12, in which the terminal position was deuterized. A possible mechanism is that Cu(OH)2 worked as a Lewis acid catalyst to activate hydrazonoester 6 and that allenyl boronate 10 [83-85] reacted with activated 6 via y-addition to afford 12. 

Palladium-catalyzed alkenylation reactions involving pyrimidines can be achieved with hydrozirconated terminal alkynes, although the reaction is carried out in the presence of zinc chloride, so transmetallation to the zinc species is presumed to occur prior to the palladium-mediated coupling <1996ACS914, B-2002MI409>. Selective reaction at the 4-position of both 2,4-dichloropyrimidine and 2,4-dichloroquinazoline can be achieved. 

TV-protected imidazole derivatives are usually deprotonated by strong bases selectively in the 2-position. This reaction, followed by transmetalation with zinc chloride, serves as the basis of the 2-arylation of the imidazole ring in the process reported by Bell and Ruddock.33 The 2-... 

Indolizines were arylated under similar conditions selectively in the 3-position (6.90.). A detailed mechanistic study of the transformation revealed that in this reaction the arylpalladium species, formed in the first step of the catalytic cycle, is attached to the indolizine core in an electrophilic substitution step, which is followed by reductive elimination. The presence of alternate routes such as Heck-type insertion, oxidative addition of the C-H bond, or transmetalation were excluded on the basis of experimental evidence.121... 

Benzyl methyl ether or allyl methyl ethers can be selectively metalated at the benzylic/allylic position by treatment with BuLi or sBuLi in THF at -40 °C to -80 C, and the resulting organolithium compounds react with primary and secondary alkyl halides, epoxides, aldehydes, or other electrophiles to yield the expected products [187, 252, 253]. With allyl ethers mixtures of a- and y-alkylated products can result [254], but transmetalation of the lithiated allyl ethers with indium yields y-metalated enol ethers, which are attacked by electrophiles at the a position (Scheme 5.29). Ethers with ft hydrogen usually undergo rapid elimination when treated with strong bases, and cannot be readily C-alkylated (last reaction, Scheme 5.29). Metalation of benzyl ethers at room temperature can also lead to metalation of the arene [255] (Section 5.3.11) or to Wittig rearrangement [256]. Epoxides have been lithiated and silylated by treatment with sBuLi at -90 °C in the presence of a diamine and a silyl chloride [257]. 

Good selectivity for transmetallation at the 2-position of 2,5-dibromopyridine 114 is obtained by using toluene as a solvent.96... 

Similar selectivities for the first cross-coupling have been observed for Suzuki and Sonogashira reactions. The Stille coupling of 3,4-diiodo-2,5-dimethylthiophene with 2-trimethylstannylthiazole stops at the monosubstitution stage. The reason for this selectivity might be that the carbon at the 3-position retards the oxidative addition and transmetalation at the adjacent 4-position. 

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