Palladium -catalyzed reactions carbanions

In the second approach55 an allylsilane was employed as carbon nucleophile in the side chain. Allylsilanes have been frequently used as masked allyl carbanions, usually in reactions with a keto function57. Palladium-catalyzed reaction of allylsilane 57 with LiCl under similar conditions as used for the other intramolecular 1,4-oxidations afforded 58 (equation 22). Interestingly, the carbochlorination over the diene was highly 1,4-syn... 

As with the silanes, some of the most useful synthetic procedures involve electrophilic attack on alkenyl and allylic stannanes. The stannanes are considerably more reactive than the corresponding silanes because there is more anionic character on carbon in the C—Sn bond and it is a weaker bond.103 104 There are also useful synthetic procedures in which organotin compounds act as carbanion donors in palladium-catalyzed reactions, as discussed in Section 8.2.3 Organotin compounds are also very important in free-radical reactions, which will be discussed in Chapter 10. 

The most important class of allylic substitutions are palladium-catalyzed reactions with so-called soft nucleophiles such as stabilized carbanions or amines, and with few exceptions, the enantioselective transformations discussed in this chapter belong to this category. The mechanism of these reactions has been firmly established and a detailed picture of the catalytic cycle can be drawn [1, 2,3,4,5,6,13,14,15]. The course of allylic substitutions catalyzed by metals other than palladium is less clear and information about the intermediates involved is scarce. 

Palladium-catalyzed cross-coupling reactions are not restricted to stannane derivatives, however, and other azaheterocyclic carbanion derivatives to have been investigated include l-methyl-2-pyrrolylmagnesium bromide and l-methyl-2-pyrrolylzinc chloride (81TL5319), l-methyl-2-indolymagnesium bromide (81TL5319), l-substituted-2- and 5-imidazolyl-... 

In the palladium-catalyzed 1,4-oxidations of conjugated dienes described so far, only heteroatom nucleophiles have been employed. There is an intrinsic problem in using free carbanions in an oxidation reaction since the oxidant can readily remove an electron and oxidize the carbanion to a radical. Furthermore, in the procedure associated with the best selectivity, i.e., the benzoquinone-based process, acid is required to regenerate the Pd(0)-benzoquinone complex to Pd(II) and hydroquinone. 

Like hydroalumination and hydrozirconation, hydroboration of alkynes also provides a convenient and Stereospecific route to alkenyl metal reagents. However, initial attempts to achieve palladium-catalyzed cross-coupling of alkenylboranes with alkenyl halides were unsuccessful, due to the poor carbanionic character of these reagents. Later, Suzuki discovered that the desired transformation could be effected in the presence of an alkoxide or hydroxide base weaker bases, such as sodium acetate or triethylamine, were not generally effective. The reaction is suitable for the preparation of ( , )-, ( ,Z)- and (Z,Z)-dienes. Since reactions of alkenylboronates are higher yielding than those of alkenylboranes, the recent availability of (Z)-l-alkenylboronates " substantially improves the Suzuki method for the preparation of (Z)-alkenes. An extension of the methodology to the synthesis of trisubstituted alkenes has also been reported. " ... 

The earlier reported palladium-catalyzed, regioselective nucleophilic substitution reaction of 1-halo-l-vinylcyclopropanes 10 to give alkylidenecyclopropanes can also be extended to stabilized carbanion nucleophiles. Use of a BINAP-modified catalyst leads to asymmetric induction with up to 47% ee. Again no ring opening of cyclopropanes was observed. 

Allylic substitutions are among the most important carbon-carbon bond-forming reactions in organic synthesis. Palladium-catalyzed allylic substitutions and their asymmetric version have been extensively studied and widely used in a variety of total syntheses [78]. The palladium catalysis mostly requires soft nucleophiles such as malonate carbanions to achieve high stereo- and regioselectivity. 

By far, the most widely used method is the alkylation of an a-sulfonyl carbanion followed by reductive removal of the sulfonyl group. Different electrophiles such as alkyl halides, sulfonates, sulfinates, acetates, oxiranes, and electron-deficient multiple bonds are employed for the formation of the new C-C bond. Palladium-catalyzed it-allylic alkylation with a-sulfonyl carbanions is also a commonly used method. After the C-C bond formation, the conditions for the final desulfonylation reaction with the appropriate reagent will depend on the structure of the sulfone intermediate. 

The final palladium-alkyl intermediate can also be trapped by hydride or carbanion reagents87,88,91. In intramolecular versions, this again leads to polycyclic products87,88 91. Thus, palladium-catalyzed polycyclization of aryl iodide 14 containing an enamide and additionally an alkene function leads, with complete stereocontrol, to tricyclic product 15 if the reaction is terminated with sodium formate, phenylzinc chloride or sodium tetraphenylborate (albeit in low yield)45. 

Stereospecific synthesis of arylidene and allylidene cyclopentanes and cyclohexanes can be achieved by palladium-catalyzed cyclization of carbanions containing a C — C triple bond in the presence of aryl or vinyl halides52 33". The reaction is stereoselective, occurring with irans selectivity. Thus, a palladacyclic intermediate, resulting from initial aryl or vinyl carbapallada-tion, is ruled out in favor of primary carbanion addition to the alkyne unit. 

The palladium(O)-catalyzed reaction of 1,3-dienes with active methylene compounds to give 1,4-addition of a hydrogen atom and a stabilized carbanion is complicated by the formation of 2 1 telomerization products [27]. It was found by Hata et al. [21a] that bidentate phosphines such as l,2-(diphenylphosphino)ethane favor formation of the 1 1 adduct. More recent studies by Jolly have shown that the use of more a-donating bidentate phosphines on palladium gave a high selectivity for 1 1 adducts [23]. For example, 1,3-butadiene reacted with 11 to give the 1,4-addition product 12 in 82% yield, along with 18% of the 1,2-addition product 13 (Eq. (7)). 

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