Alkylation palladium assisted

Table 6. Palladium-Assisted Alkylation of Chiral y-Butyrolactones with Chiral Phosphates...

Table 7. Charge-Directed Palladium-Assisted Alkylation of Vinyl y-Rulyro-lactones with Sodium Dimethyl Malonate...

In general, allyl ethers are less reactive than esters and therefore rarely used as substrates in the palladium-assisted alkylation with soft nucleophiles. Phenyl a- or )5-D-eor//jro-hex-2-enopyra-nosides react with a variety of soft carbanions under neutral conditions to give the a- or t -C -g]ycopyranosides, respectively in good to excellent yields both stereoselectively and with complete regioselectivity88. Since the liberated phenoxide ion deprotonates the active methylene compounds, no external base has to be added. 

Table 9. Palladium-Assisted Alkylation of Phenyl az/l-n-err/Ara-Hex -enopyranosides with Soft Nucleophiles...

Cyclic vinyl epoxides are versatile building blocks (Table 11) which have been used in palladium-assisted routes to carbocyclic nucleosides. A formal synthesis of ( )-aris-teromycin101, the carbocyclic analog of adenosine, has been accomplished employing ni-tromethane as the nucleophile which serves as an acyl anion equivalent (Table 11. entry 2). The aldehyde is released by subsequent basic potassium permanganate oxidation. If nitromethane is used diluted in tetrahydrofuran, then a mixture of mono- and bis-alkylated product is formed. Whereas the alkylation of cyclohexenoxide with dimethyl malonate proceeds in a 1,4-crs fashion under palladium(O) catalysis, the 1.2-/ra/i.v-product is formed under basic conditions in the absence of the palladium(O) catalyst. 

The complementary nature of the purely basic and the palladium-assisted alkylation in combination with the chemoselective epoxidation of either of the two double bonds of 2-phenylsul-fonyl-1,3-dienes102 makes these substrates useful synthons for multicoupling reactions. By changing the order of nucleophilic addition and epoxidation, three isomers of the alkylated hydroxy vinyl sulfone are available one of them, that depicted, by palladium-promoted reaction. Without sodium hydride, or in the absence of a nucleophile, / -hydride elimination to the corresponding dienol occurs. 

As alluded to above, this version of the Jt-allyl palladium reaction uses an allylic acetate or chloride. The use of the acetate is more common because acetate is a much weaker nucleophile than chloride. When it involves a substrate where diastereomeric products can result, the stereochemistry of the nucleophilic displacement is an important issue. Palladium assisted alkylation proceeds with net retention of configuration of the acetate or chloride, as seen in the conversion of 375 to 376.223e,f... 

Matrix-assisted laser desorption/ionization (MALDI) mass spectrometry has contributed remarkably to unravelling the termination and initiation steps of the styrene/CO copolymerisation catalysed by the highly active bis-chelated complex [Pd(bipy)2](Pp5)2 in TFE [40]. Chain-end group analysis of the material produced in the absence of BQ showed that the termination by P-H elimination is accompanied by three different initiators two palladium alkyls from Pd-H formed by reaction of the precursor with CO and water (a and b) and a palladium carboalkoxy species formed by reaction of the precursor with the fluorinated alcohol and CO (c) (Chart 7.4). The suppression of the chain-transfer by alcoholysis was proposed to be responsible for the enhanced stability of the palladium acyl intermediates and hence for the high molecular weight of the copolymers produced. 

Traceless solid-phase synthesis of 2,6,9-trisubstituted purines from resin-bound 6-thiopurines <02T7911>, and microwave assisted solid-phase synthesis of 2,6,9-trisubstituted purines <02TL6169> have been described. A resin-capture and release strategy toward combinatorial libraries of 2,6,9-trisubstituted purines has been reported <02JCO183>. Alkylated purines chlorinated at the 6,8- or 2,6,8-positions can be captured onto a solid support and further elaborated by aromatic substitution or via palladium catalyzed crosscoupling reactions <02JA1594>. 

In addition to the most important 1,2-difunctionalization assisted or catalyzed by palladium(II) complexes, a catalytic 1,1-arylamination process of alkenes, applied to the construction of nitrogen heterocycles from 4-pentenylamides, was realized29,30. The mechanism involves the formation of arylpalladium chloride from alkyl(aryl)stannanes, the addition to the alkene, the isomerization of the adduct to the more stable benzylic palladium complex, and the displacement of palladium by an internal nitrogen nucleophile. In the presence of a substituent, mixtures of diastereomers were generally obtained. 

The highest enantiomeric excess in the palladium(0)-assisted enantiosclcctive alkylation of racemic 3-cycloalkenyl acetate has so far been observed with the chiral ligands 2, 3a and 3b60-61 (Table 17). The addition of tetrahexylammonium bromide dramatically increases enantioselec-tivity in the case of ligand 2, as does changing the solvent from tetrahydrofuran to dichloro-methane. which is believed to enhance the formation of dimeric ionic salts of the nucleophile. In contrast, additives such as tetraalkylammonium salts or crown ethers diminish the enantiomeric excess in reactions catalyzed by the phosphinoaryl oxazoline ligands 3a and 3b. bearing a chiral phosphorus on the aryl moiety. 

The influence of double stereodifferentiation on palladium(0)-assisted alkylation of soft car-banions has not yet been thoroughly investigated. Coupling of a chiral ally ligand, prepared from a- or //-phenyl-n-cn // ru-hcx-2-enopyranoside (see Section 1.5.6.1.2.1.)4 with a prostereogenic soft carbanion in the presence of Diop has not improved the simple diastereoselectivity. 

Other examples of microwave-assisted catalysis include allylic alkylation, both palladium catalyzed and molybdenum catalyzed. In the latter case, air stable precursor complexes could be used under non-inert conditions. Microwave-enhanced Pauson-Khand reactions have also been reported, as have hydroamination of alkynes, and metathesis of functionalized alkynes. " Recently, microwave enhancement has been applied to C-H activation reactions, for example, for the formation of functionalized heterocycles, allowing the reaction to be performed with no solvent purification and minimal precautions to exclude air. A solvent-free chelation-assisted hydroacylation... 

Alexander Mikhaylovich Saytzev (Saytzeff) (Kazan 20 June 1841 (O.S.)-2 September 1910) studied with Kolbe in Marburg and Leipzig, and was professor in the University of Kazan. He discovered the synthesis of primary and secondary alcohols from esters, ketones, and aldehydes by the action of zinc and alkyl iodides (see Reformatsky, p. 858). He also discovered aliphatic sulphoxides. His brother Mikhayl Mikhaylovich (b. Kazan, 30 August 1845), at first his assistant and later manager of a chemical works in Kazan, discovered the reduction of acid chlorides to aldehydes by hydrogen gas in presence of palladium. ... 

Many arylations are assisted by functional groups that promote ortho-metallation. Thus, for example, acetanihdes react with arylsilanes at the ortho position via pal-ladacycles 78 and 79 to form derivatives 80 (Scheme 11.27) [84]. Mechanistically, this transformation is similar to a cross-coupling reaction, in which the oxidative addition step is replaced by the ortho-metallation, although in this case the Pd(0) intermediate must be oxidized in situ to generate the reactive Pd(ll) species. Unsubstituted benzylamines and N-methylbenzylamine are ortho-arylated with Pd(OAc)2 in the presence of trifluoroacetic acid (TFA) and silver acetate [85], and a mechanism which differs from the usual Pd(0)/Pd(II) catalytic cycle was suggested for this. Ortho-alkylation was also observed in the palladium-catalyzed... 

The possibilities for the formation of carbon—carbon bonds involving aromatic compounds have been enormously enhanced by the use of transition metal catalysts, and this area has been the subject of several reviews. Some of these concentrate on the applications of specific metals, and there have been surveys of the use of compounds of silver, copper and nickel,mthenium, and palladium in catalysis. The metalation of carbon-hydrogen bonds, preceding functionalization, may be aided by carboxylate ions, and this subject has also been reviewed. There is evidence here for concerted base-assisted deprotonation as shown in (10). In the carboxylate-assisted reaction of aryl ketimines with alkyl halides, a ruthenium-bonded intermediate (11) has been proposed, which subsequently adds the alkyl halide. " ... 

Shabashov D, Daugulis O (2010) Auxiliary-assisted palladium-catalyzed arylation and alkylation of sp2 and sp3 carbon — hydrogen bonds. J Am Chem Soc 132(11) 3965-3972... 

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