Alkylations palladium catalysis

Keywords Allylic alkylation Asymmetric catalysis Decarboxylation Enolate a-alkylation Palladium catalysis PHOX ligands Quaternary stereocenters... 

Allyl sulphones can be converted to dienes by alkylation and elimination of sulphinic acid under basic conditions (equation 64)105. Several vitamin A related polyenes have been synthesized following this two-step protocol (Table 10)106. The poor leaving-group ability of the arylsulphonyl group requires treatment with strong base for elimination. However, elimination of the allylsulphonyl group takes place readily under palladium catalysis (equation 65)107. Vinyl sulphones can be converted to dienes via Michael addition, alkylation with allyl halides and elimination of sulphinic acid sequence (equation 66)108. 

The three-component synthesis of benzo and naphthofuran-2(3H)-ones from the corresponding aromatic alcohol (phenols or naphthols) with aldehydes and CO (5 bar) can be performed under palladium catalysis (Scheme 16) [59,60]. The mechanism involves consecutive Friedel-Crafts-type aromatic alkylation and carbonylation of an intermediate benzylpalla-dium species. The presence of acidic cocatalysts such as TFA and electron-donating substituents in ortho-position (no reaction with benzyl alcohol ) proved beneficial for both reaction steps. 

The mechanism of propene/CO copolymerisation by palladium catalysis is essentially analogous to those of ethene and styrene (i. e., chain propagation proceeds via alternating insertions of CO into Pd-alkyl and alkene into Pd-acyl controlled by p-chelates) [1]. 

Recently, Fu and coworkers have shown that secondary alkyl halides do not react under palladium catalysis since the oxidative addition is too slow. They have demonstrated that this lack of reactivity is mainly due to steric effects. Under iron catalysis, the coupling reaction is clearly less sensitive to such steric influences since cyclic and acyclic secondary alkyl bromides were used successfully. Such a difference could be explained by the mechanism proposed by Cahiez and coworkers (Figure 2). Contrary to Pd°, which reacts with alkyl halides according to a concerted oxidative addition mechanism, the iron-catalyzed reaction could involve a two-step monoelectronic transfer. 

Alkylation and deprotection of N-protected aminomethylphosphonate esters 6 are shown in Scheme 6. The nitrogen is protected as the imine derived from benzophenone or a benz-aldehyde, and a variety of conditions are used for deprotonation and alkylation (Table 2). The benzaldehyde imine of aminomethylphosphonate can be deprotonated with LDA and alkylated with electrophilic halides (entries 1 and 2). For the best yields, saturated alkyl bromides require an equivalent of HMPA as an additive. 36 Allylic esters can be added to the carbanion with palladium catalysis (entries 3-7). 37,38 For large-scale production, phase-transfer catalysis appears to be effective and inexpensive (entries 8-12). 39,40 ... 

Alkylation of Protected Aminomethylphosphonate Using Palladium Catalysis General Procedure 138 ... 

Halides react with carbon monoxide in the presence of a source of a second alkyl group, with palladium catalysis, to give ketones as shown in equation 148. 

Among common carbon-carbon bond formation reactions involving carbanionic species, the nucleophilic substitution of alkyl halides with active methylene compounds in the presence of a base, e. g., malonic and acetoacetic ester syntheses, is one of the most well documented important methods in organic synthesis. Ketone enolates and protected ones such as vinyl silyl ethers are also versatile nucleophiles for the reaction with various electrophiles including alkyl halides. On the other hand, for the reaction of aryl halides with such nucleophiles to proceed, photostimulation or addition of transition metal catalysts or promoters is usually required, unless the halides are activated by strong electron-withdrawing substituents [7]. Of the metal species, palladium has proved to be especially useful, while copper may also be used in some reactions [81. Thus, aryl halides can react with a variety of substrates having acidic C-H bonds under palladium catalysis. 

Substitution of chlorine atoms in 2.4-dichloroquinazoline with alkyl groups is readily effected under the influence of palladium catalysis with trialkylaluminum acting as donor of the alkyl group. Selectivity for position 4 in 2,4-dichloroquinazoline can be achieved with trimethyl- and triisobutylaluminum under the influence of tetrakis(triphenylphosphane)palladium(0) as catalyst. In the presence of another molar equivalent or more of trialkylaluminum, products 14 which carry the same or a different alkyl group in the 2-position are formed. ... 

With palladium catalysis, both 2,6-dichloropyrazine 3 and chloropyrazine-Woxide 4 were methylated using trimethylaluminum to give adducts 5 and 6, respectively [12]. Trimethylaluminum was found to be a useful reagent for the alkylation of substituted pyrazines and their Woxides [12]. 

The scope of vinyl metals as sources of nucleophilic vinyl groups is very great. As well as the expected electrophiles such as halogens, alkyl and acyl halides, aldehydes and ketones, unsaturated carbonyl compounds and epoxides, they also combine with aryl and alkenyl halides with palladium catalysis. The usual stereochemical course is retention at the vinyl group. It is necessary to decide whether the vinyl metal is reactive enough or whether it must first be transformed into an ate complex. Since most of these vinyl metals can be converted into each other with retention, this is an unusually versatile group of reagents. 

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