5- catalysed alkylation

Salaun and de Meijere s groups have applied successfully the intramolecular PKR on 1-cyclopropylidene-1,6-enynes 421-426 (Table 34) [108], accessible via the Pd(0) catalysed alkylation of stabilized carbanions with 1-vinylcyclo-propanes 1-substituted with leaving groups [3a, 109]. 

Alkylation of potentially tautomeric heteroaromatic systems under basic phase-transfer catalytic conditions normally occurs on the softer heteroatom [cf 57]. Thus, although 2- and 4-pyridones are alkylated on the annular nitrogen atom and the exocyclic oxygen atom, -alkylation of the 2-pyridones predominates to the extent of ca. 5 1 (or greater under soliddiquid reaction conditions [58]), whereas the relative predominance of A -alkylation of the 4-isomer is only ca. 3 1 [59] (Table 5.37 and 5.38). These ratios are comparable with those obtained for the base-catalysed alkylation of the pyridones by traditional methods and, not unexpectedly, S-alkyla-tion of the corresponding pyridthiones occurs to the total exclusion of A-alkylation [60]. Catalysed soliddiquid acylation has also been reported [58]. 

Potentially tautomeric pyrimidines and purines are /V-alkylated under two-phase conditions, using tetra-n-butylammonium bromide or Aliquat as the catalyst [75-77], Alkylation of, for example, uracil, thiamine, and cytosine yield the 1-mono-and 1,3-dialkylated derivatives [77-81]. Theobromine and other xanthines are alkylated at N1 and/or at N3, but adenine is preferentially alkylated at N9 (70-80%), with smaller amounts of the N3-alkylated derivative (20-25%), under the basic two-phase conditions [76]. These observations should be compared with the preferential alkylation at N3 under neutral conditions. The procedure is of importance in the derivatization of nucleic acids and it has been developed for the /V-alkylation of nucleosides and nucleotides using haloalkanes or trialkyl phosphates in the presence of tetra-n-butylammonium fluoride [80], Under analogous conditions, pyrimidine nucleosides are O-acylated [79]. The catalysed alkylation reactions have been extended to the glycosidation of pyrrolo[2,3-r/]pyrimidines, pyrrolo[3,2-c]pyridines, and pyrazolo[3,4-r/]pyrimidines (e.g. Scheme 5.20) [e.g. 82-88] as a route to potentially biologically active azapurine analogues. 

The catalysed alkylation of l//,4//-pyrazol-5-ones is solvent dependent. In benzene, bis-alkylation occurs at the 4-position whereas, in a carbon disulphide benzene mixture, O-alkylation is observed, although the major product (4, Scheme 5.22) results from nucleophilic attack by the pyrazolone on the carbon disulphide, followed by alkylation of the dithiolate dianion [92]. The catalysed reaction of 2-thiono-3-aryl-thiazolidin-4-ones with alkylating agents under soliddiquid two-phase conditions results in alkylation at the 5-position (60-80%) [93]. The aldol condensation of the thiazolidinones with aryl aldehydes is also catalysed by quaternary ammonium salts. 

Catalysed alkylation of tosylmethylisocyanate (TOSMIC) [63, 64] has extended its versatility in the preparation of l, 4-dicarbonyl compounds and as a l, 3-dipolar precursor for the synthesis of heterocyclic compounds. The alkylation reactions should not be conducted in carbon disulphide, as nucleophilic attack by the methylene group on the carbon disulphide leads, after ring closure and S-alkylation, to a 4-alkylthio-1,3-thiazole system [65]. 

The phase-transfer catalysed alkylation of S-cyanomethyl dithiocarbamates provides a high yielding and convenient route to aldehydes (from monoalkylation) and ketones (from dialkylation) [128]. The procedure has been used to produce a range of alicyclic and small-ring ketones (>85%). 

The kinetics of the base-catalysed alkylation of 5-substituted 3-nitrotriazoles with methyl vinyl ketone to give the N(l)-3-butanone derivative has been studied and the reaction was shown to be first order in both mvk and the 3-nitrotriazolium anion <90JOU1170>. 

Zeolite catalysed alkylation of polynuclear aromatics is considered to be simultaneously governed by several mechanisms. To achieve highly shape-selective catalysis, it is essential that the pore size precisely corresponds to the molecular dimensions of reactants and products, and to the transition state of the reaction intermediates. 

The product distribution in the zeolite-catalysed alkylation of polynuclear aromatics depends on the structure of zeolite pores. High regioselectivities were observed in the HM catalysed isopropylation of polynuclear aromatics, such as biphenyl, naphthalene, p-terphenyl, and dibenzofuran, to yield predominantly the least bulky products e.g., 4,4 -DIPB for biphenyl, and 2,6-DIPN for naphthalene. These reactions are controlled by steric restriction at the transition state inside the pores and by the entrance of intermediate products molecules into the pores. On the other hand, the catalysts with large-pore HY and HL zeolite are controlled at low temperature by the electron density of the reactant molecule and at higher temperature by the stability of the product molecules because their pores have enough space for a transition state, which allow the formation of all corresponding isomers. 

Drs. Yoshihiro Sugi and Yoshihiro Kubota next present a review of the zeolite-catalysed alkylation of polynuclear aromatics. Their chapter gives an especially useful and general approach to understanding deactivation in these materials. 

Good results have been achieved in phosphonio-catalysed alkylation of active methylene compounds and imides which may be steroselective873 (equation 269). Aqueous sodium hydroxide deprotonation of the phosphonium salt itself in view of a Wittig reaction is... 

The metabolites are then simultaneously eluted from the disk and derivatised to their ethyl esters by adding 100 jtl of ethyl iodide and heating the vial at 100 °C for one hour. Using this approach, only a single sample is analysed, and because the disk-catalysed alkylation reaction does not transesterify Dacthal, the speciation of Dacthal is maintained. In addition, no sample clean-up steps are required, and only a total of 5 ml of nonchlorinated organic solvent is used. 

As an extension of the oxidative carbonylation using alkyl nitrite, malonate 238 can be prepared by the oxidative carbonylation of ketene (237) [la,143], Also, acetonedicarboxylate (240) is prepared by the Pd-catalysed, alkyl nitrite-mediated oxidative carbonylation of diketene (239) [la, 144]. 

Regio- and stereo-selective synthesis of annulated arene heterocycles and carbocy-cles having a halo functionality is accomplished by Sm(OTf)3-catalysed alkylation of (S) arenes by a tethered alkene group using /V-halosuccinimide as a halogen source [e.g. 

Experimental KIEs and theory were used to investigate the mechanism of the palladium-catalysed alkylation of 1,1-dimethylallylacetate (2) by dimethyl malonate.6 A significant 12C/13C KIE of 1.037 at C(l) and small KIEs (1.00) at C(2) and C(3)... 

Palladium or nickel catalysed cross-coupling involving alkyl, allyl, propargyl, and benzyl groups 2.3.1 Palladium or nickel catalysed alkylation... 

Microwave heating and catalysis have been successfully used in the solvent-free synthesis of cosmetic fatty esters (Villa et al., 2003). Two kinds of reaction were performed acid-catalysed esterification (Figure 3.11) and phase-transfer catalysed alkylations, both reactions affording near quantitative yields when microwave heating was used. It should be noted that diethyl ether and water were used in the purification of the product, and alternative purification/separation procedures would be required if this process was performed on an industrial scale, due to the flammability risk of diethyl ether. 

A gold-catalysed alkylation of arenes with epoxides has also recently been discovered treating phenoxymethyloxiranes with AuCl3/3AgOTf (Tf = CF3SO2- triflate is trifluoromethanesulfonate i.e. OTf) (2.5 mol) in dichloromethane at 323 K yielded exclusively endo addition product 3-chromanols in good yield in 3h 37... 

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