Phase-transfer glycolate alkylation

The utilization of polar polymers and novel N-alkyl-4-(N, N -dialklamino)pyridinium sedts as stable phase transfer catalysts for nucleophilic aromatic substitution are reported. Polar polymers such as poly (ethylene glycol) or polyvinylpyrrolidone are thermally stable, but provide only slow rates. The dialkylaminopyridininium salts are very active catalysts, and are up to 100 times more stable than tetrabutylammonium bromide, allowing recovery and reuse of catalyst. The utilization of b is-dialkylaminopypridinium salts for phase-transfer catalyzed nucleophilic substitution by bisphenoxides leads to enhanced rates, and the requirement of less catalyst. Experimental details are provided. 

Neumann, R. and Sasson, Y., Poly(ethylene glycols) as phase-transfer catalysts in the alkoxylation of halobenzenes of alkyl aryl ethers, Tetrahedron, 1983, 39, 3437. 

N-Alkylation of 1,2,3-triazoles and benzotriazoles is readily achieved using (1) alkyl halides, dialkyl sulfates, diazoalkanes, and jS-tosylates or (2) the Mannich reaction. When alkyl halides are used, sodium alkoxide, sodium hydride, or sodium hydroxide is usually employed as the base. The N-alkylation of benzotriazole with alkyl halides proceeds efficiently using powdered NaOH as the base in DMF. The highest yields (80100%) of the alkylated benzotriazoles are obtained when a fourfold excess of NaOFl is employed. A-Alkylbenzotriazoles have been prepared from benzotriazole and alkyl halides using phase-transfer catalysts, e.g., KOFI, benzene, tetrabutyl-ammonium salts or KOH, benzene, polyethylene glycol. 

The chloroform/base/phase-transfer catalyst method has proved to be useful for the preparation of 2,2-dichIorocyclopropyl ketones on condition that the double bond in the starting ketones is substituted in the a-position by an alkyl group. ° Both benzyltriethylammonium chloride and polyethylene glycol (PEG 1500, in the presence of powdered potassium hydroxide) are effective catalysts for these reactions. 

Even carbowax (a chemically and thermally stable poly(ethylene glycol), when adsorbed on an inorganic salt with no other solid support, may act as a very efficient gas-solid phase-transfer catalyst. This system has been employed, for example, in the Williamson synthesis of ethers and thioethers, starting from alkyl halides and phenols or thiols in the presence of potassium carbonate as a base Gas-solid PTC shows the advantage that pure products are obtained directly, due to the absence of aqueous and organic solvents. 

Well known examples are oxidations with Mn04 where the latter is transferred into an apolar organic medium such as benzene, purple benzene , by complexed macrocyclic polyethers or quaternary cations, both in liquid-liquid and solid-liquid phase-transfer systems This procedure eliminates the self-catalyzed decomposition of Mn04 which occurs with evolution of O2. Olefins, alcohols, alkylated arenes, etc. are thus oxidized to carboxylic acids, ketones, aldehydes, or glycols. 

The sonochemical alkylation at a nitrogen atom appeared for the first time in a paper by Davidson et al A t)q)ical example is given in Eq. 48, and many others are known. With carbazole, the rate increase is high, ca. 50 times, but the presence of polyethylene glycol methyl ether as a PTC is necessary. Alkylation of macrocyclic amines was improved by sonication in the presence of potassium hydroxide (Eq. 49), and quatemization is avoided. A practically quantitative yield is observed, even without PTC, but in this particular case, a phase transfer autocatalytic mechanism is probable. o... 

Triphase catalysts were also used for C-alkylations (Komeili-Zadeh, 1978) and have been shown to promote asymmetric addition in carbene addition reactions (Chiellini and Solaro, 1977 Colonna et al., 1978). Ammonium groups have been replaced by phosphoric triamides (Tomoi et al., 1978), phosphonium groups (Tundo, 1978), and polyethylene glycol (Regen and Dulak, 1977) to provide alternate phase-transfer agents. 

Meanwhile, polyethylene glycol is reported to act as a phase-transfer catalystlOjll, and it is also shown to form a double helix in complexing with an alkaline metal cationl2. If we use an isotactic optically active polymer back-bone, there may be a chance to see as3mmietric selection in the esterification reactions of chiral acid salts and achiral alkyl halides in the presence of... 

Phase transfer catalysis can be effective in triphase solid/solid/liquid mixtures. Solid potassium phenoxide and solid sodium iodide react with alkyl halides in the presence of (64). The solid/solid/liquid method also succeeds for hypochlorite oxidation of secondary alcohols and periodate oxidation of glycols catalyzed by commercial AERs (3). 

Andrus MB, Hicken EJ, Stephens JC, Bedke DK. Asymmetric phase-transfer catalyzed glycolate alkylation, investigation of the scope, and application to the synthesis of (—)-ragaglitazar. J. Org. Chem. 2005 70(23) 9470-9479. 

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