Allyhc alkylation

Recently, this methodology has been extended to the couphng of alkyl, allyhc, 1-alkenyl and 1-alkynyl halides with 1-alkenyl and even alkyl boron reagents. 

N-Alkylpyrroles may be obtained by the Knorr synthesis or by the reaction of the pyrrolyl metallates, ie, Na, K, and Tl, with alkyl haUdes such as iodomethane, eg, 1-methylpyrrole [96-54-8]. Alkylation of pyrroles at the other ring positions can be carried out under mild conditions with allyhc or hensylic hahdes or under more stringent conditions (100—150°C) with CH I. However, unless most of the other ring positions are blocked, poly alkylation and polymerisation tend to occur. N-Alkylation of pyrroles is favored by polar solvents and weakly coordinating cations (Na", K" ). More strongly coordinating cations (Li", Mg " ) lead to more C-alkylation. 

However, because PVC is largely composed of alternating CH2 and CHCl groups, each elimination of HCl also produces an allyhc chlorine (eq. 9). The allyhc chlorine is less stable than the alkyl chlorine, ie, the production of allyhc chlorine lowers the overall stabihty. 

AllyHc alkylation o( ally alcohols m the presence of copper Iodide and phosphmimines... 

The use of chiral transition-metal complexes as catalysts for stereoselective C-C bond forming reactions has developed into a topic of fimdamental importance. The allyhc alkylation is one of the best known of this type of reaction. It allows the Pd-catalyzed substitution of a suitable leaving group in the allylic position by a soft nucleophile. 

One of the first efficient catalytic palladium systems for asymmetric allyhc alkylation that does not involve phosphines has been reported by Pfaltz [37], who used bisoxazohnes. 

Fig. 2.20 Chiral Pd-NHC catalysts and ligands used for the asymmetric allyhc alkylation...

Scheme 2.25 Generation of ruthenium catalysts for the allyhc alkylation of cinnamyl carbonate...

The stereospecific rhodium-catalyzed allyhc hnchpin cross-couphng reaction provides an expeditious route to stereotetrads (Scheme 10.5). This study demonstrated that improved stereospecificity could be obtained at lower temperature for the formation of the alkylation product 18 (2° 1°=24 1 ds=26 l compare Tab. 10.2, entry 1). Krapcho... 

Tab. 10.8 summarizes the application of rhodium-catalyzed allylic etherification to a variety of racemic secondary allylic carbonates, using the copper(I) alkoxide derived from 2,4-dimethyl-3-pentanol vide intro). Although the allyhc etherification is tolerant of linear alkyl substituents (entries 1-4), branched derivatives proved more challenging in terms of selectivity and turnover, the y-position being the first point at which branching does not appear to interfere with the substitution (entry 5). The allylic etherification also proved feasible for hydroxymethyl, alkene, and aryl substituents, albeit with lower selectivity (entries 6-9). This transformation is remarkably tolerant, given that the classical alkylation of a hindered metal alkoxide with a secondary alkyl halide would undoubtedly lead to elimination. Hence, regioselective rhodium-catalyzed allylic etherification with a secondary copper(l) alkoxide provides an important method for the synthesis of allylic ethers. 

Enantioselective transition metal-catalyzed allyhc alkylation has stimulated immense interest due to its potential synthetic utihty [1 b]. Although excellent enantioselectivities have been obtained for a wide variety of cychc and acyclic aUyhc alcohol derivatives, using a wide range of chiral transition metal complexes, the ability to also control regioselectivity has proven challenging. In hght of the excellent selectivities observed for rhodium-catalyzed allyhc substitution, it would seem reasonable to assume that the enantioselective rhodium-catalyzed version may provide the definitive solution to this problem. 

While reaction of the acetate 40 as well as the acetyl- and phthalimide derivatives of chiral amine (41b and 41c) proceeded with erythro diastereoselectivity (in accordance with the classical cis effect, minimization of 1,3-allyhc strain) (Table 6, entries 8, 10, 11), for the allylic alcohols 39, primary allyhc amine 41a, silyl enol ethers 42 and enol ether 43 threo selectivity was observed (Table 6, entries 1-7, 9, 12-14) (see also Scheme 24). For allyhc alcohols with an alkyl group R cis to the substituent carrying the hydroxyl group, diastereoselectivity was high (Table 6, entries 1-7) in contrast, stereoselection was low for allylic alcohols which lack such an R cis) substituent (substrates 39h and 39i, see Figure 4). 

Palladium-CatalYzed AllyHc Alkylation of Sulfur and Oxygen Nucleophiles 217... 

SCHEME 15. Synthesis of bifunctional building blocks through copper/Taniaphos-catalyzed allyhc alkylation... 

A simple method for the direct catalytic allylic alkylation of aldehydes and cyclic ketones has been developed.26 The direct catalytic highly chemo- and regio-selective intermolecular a-allyhc alkylation reaction has been mediated by an unprecedented combination of palladium and enamine catalysis which furnishes a-allylic alkylated aldehydes and cyclic ketones in high yield. 

An in-depth study of platinum allyhc alkylation and subsequent comparison to ligand-identical palladium catalysts was done by Blacker et al. The aUylic alkylation of diphenyl-2-enyl acetate with dimethyl malonate, (equation 73), reveals activity for a variety of complexes with activity restricted by the source of zerovalent platinum (Table 1). Nonactive complexes are thought to be less prone to dissociation into coordinatively unsaturated catalytical active species. 

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