Arylation proton abstraction

Rearrangement to an open chain imine (165) provides an intermediate whose acidity toward lithiomethylthiazole (162) is rather pronounced. Proton abstraction by 162 gives the dilithio intermediate (166) and regenerates 2-methylthiazole for further reaction. During the final hydrolysis, 166 affords the dimer (167) that could be isolated by molecular distillation (433). A proof in favor of this mechanism is that when a large excess of butyllithium is added to (161) at -78°C and the solution is allowed to warm to room temperature, the deuterolysis affords only dideuterated thiazole (170), with no evidence of any dimeric product. Under these conditions almost complete dianion formation results (169), and the concentration of nonmetalated thiazole is nil. (Scheme 79). This dimerization bears some similitude with the formation of 2-methylthia-zolium anhydrobase dealt with in Chapter DC. Meyers could confirm the independence of the formation of the benzyl-type (172) and the aryl-type... 

Thiophenium fluorosulfonate, 1,2,3,4,5-tetramethy 1-ylide, 4, 724 Thiophenium salts aromaticity, 4, 724 proton abstraction, 4, 766 pyramidal inversion barrier, 4, 724 structure, 4, 715 synthesis, 4, 723-724 Thiophenium salts, 1-alkyl-solvolysis, 4, 766 UV spectra, 4, 766 Thiophenium salts, aryl-synthesis, 4, 726... 

The proton abstraction typically requires strong bases although weaker bases can be employed if the a-carbon is substituted with an additional activating group, such as an aryl group. " ° Deprotonation of chiral arylmethyloxazolines followed by alkylation gave modest levels of diastereoselection (up to 60% de). " Deprotonation of appropriately substituted 2-(allyloxymethyl)oxazolines resulted in... 

In this section the reactions of selenophenes and tellurophenes with metal alkoxides, alkyls, aryls and amides will be considered. These reactions result primarily in proton abstraction and, in the monocyclic and benzo[6] fused systems, protons are removed preferentially from positions a to the heteroatom. In conformity with the general format of the reactivity sections in this work, the reactivity of the metal derivatives formed is dealt with in Section 3.16.8.8 on metalloid substituents. 

Houghten and co-workers[145] introduced a method for combinatorial synthesis of a per-alkylated peptide library using nonspecific N-alkylation. The peptides were synthesized by SMPS methodology 146 in combination with repetitive amide N-alkylation on the solid support after each coupling step. Peptides were synthesized on MBHA-PSty resin using Fmoc chemistry. After Fmoc deprotection the a-amino group was protected by Trt to prevent N -alkylation and to allow only amide alkylation. The on-resin amide alkylation was achieved by amide proton abstraction using LiOtBu in THF followed by nonfunctionalized alkyl and aryl halides in DMSO. 

Step 3 Completion of addition phase. The aryl anion abstracts a proton from the ammonia used as the solvent in the reaction. 

Protons at C2 of imidazole 1-oxides 228 are acidic and are exchanged with deuterium even in weakly acidic solution. The exchange rate increases with increasing pH (2004S2678). Although the mechanism is not fully understood, the palladium-catalyzed direct arylation of imidazole 1-oxides most likely involves deprotonation so that the observed regi-oselective arylation reflects the propensity to proton abstraction found to decrease in the order C2 > C5 > C4 (2009JA3291). 

Garcia-Cuadrado D, Braga AAC, Maseras F, Echavarren AM (2006) Proton abstraction mechanism for the palladium-catalyzed intramolecular arylation. J Am Chem Soc 128 1066-1067... 

Ozdemir I, Demir S, (Jetinkaya B, Gourlaouen C, Maseras F, Bruneau C, Dixneuf PH (2008) Direct arylation of arene C-H bonds by cooperative action of NHCarbene-Ruthenium(II) catalyst and carbonate via proton abstraction mechanism. J Am Chem Soc 130 1156-1157... 

Substrate—Aromatic bromides or iodides (Ar-X) are rapidly converted to the corresponding aryllithium (Ar-Li) when treated with 1 molar equivalent of n-BuLi or 2 molar equivalents of (-BuLi. However, some substrates may rearrange to a more thermodynamically stable aryllithium via abstraction of a proton from a more acidic site, and this can lead to the formation of unwanted impurities (Scheme 12.5, eq. 2). Similarly, proton abstraction from aryl bromide substrates that contain an ortfto-directing metalation group (DMG) may lead to impurities in the final product. ... 

Isotope effects are also inconsistent with an electrophilic aromatic substitution. Thus, intramolecular competition experiments between phenyl and pentadeutero-phenyl groups led to the determination of intramolecular isotope effects kH/feo = 5.0 (135 °C) and = 6.7 (100°C) for this arylation [37]. This led to the proposal of a mechanism based on a proton-abstraction for this reaction [37], which is in line with the findings of other studies [25e. A related mechanism, in which acetate acts as the basic ligand, has been proposed for the cyclometallation of benzyUc amines with Pd(OAc)2 [38]. 

Arylation reactions with the bidentate phosphines most likely proceed by the intermoiecuiar proton-abstraction mechanism, which is supported by DFT calculations as shown in the transformation of 41 into 42 (Scheme 11.12) [39]. Although the addition of pivalic acid has a beneficial effect in many cases, the fact that the... 

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