Alternative phase transfer catalysts

A newer and equally effective way of swapping azides with halides (bromines or iodines) is in the use of phase transfer catalysts [68]. Strike wouldn t expect an underground chemist to purchase the exotic catalyst Aliquat 336 which the investigators in this reference used to get yields approaching 100% but an alternative catalyst of... 

A cousin to this reduction is one using stannous chloride (a.k.a. SnCb, a.k.a. Tin chloride) which is done exactly as the calcium one except that about lOOg of SnCb is used in place of the Mg or Ca and the addition occurs at room temperature and the solution is stirred for one hour rather than 15 minutes. Some very good reductions that operate almost exclusively at room temperature with no pressure and give almost 100% yields are to follow. The only reason Strike did not detail these methods is that some of the chemicals involved are a little less common than Strike is used to but all are available to the public. These alternatives include acetlylacetone and triethylamine [73], propanedithlol and trieth-ylamine [74], triphenylphosphine [75], NaBH4 with phase transfer catalyst [76], H2S and pyridine [77], and palladium hydrox-ide/carbon with hydrazine [78], stannous chloride dihydrate [85]. 

Alternatively, the Sn2 nucleophilic substitution reaction between alcohols (phenols) and organic halides under basic conditions is the classical Williamson ether synthesis. Recently, it was found that water-soluble calix[n]arenes (n = 4, 6, 8) containing trimethylammonium groups on the upper rim (e.g., calix[4]arene 5.2) were inverse phase-transfer catalysts for alkylation of alcohols and phenols with alkyl halides in aqueous NaOH solution to give the corresponding alkylated products in good-to-high yields.56... 

Chiral crown ethers such as 13 are suitable alternatives to the ammonium salts and not decomposed under alkaline conditions. They usually have higher catalyst turnover than the chiral ammonium salts, and the design of catalysts will be much easier. However, they are, in general, costly and difficult to prepare on large scale. Polyols (eg., (RR)-TADDOL14) also serve as phase transfer catalysts. 

It was a result of demand from industry in the mid-1960s for an alternative to be found for the expensive traditional synthetic procedures that led to the evolution of phase-transfer catalysis in which hydrophilic anions could be transferred into an organic medium. Several phase-transfer catalysts are available quaternary ammonium, phosphonium and arsonium salts, crown ethers, cryptands and polyethylene glycols. Of these, the quaternary ammonium salts are the most versatile and, compared with the crown ethers, which have many applications, they have the advantage of being relatively cheap, stable and non-toxic [1, 2]. Additionally, comparisons of the efficiencies of the various catalysts have shown that the ammonium salts are superior to the crown ethers and polyethylene glycols and comparable with the cryptands [e.g. 3, 4], which have fewer proven applications and require higher... 

As an alternative to the oxidation of sulphides and sulphoxides (see Chapter 10), sulphones can be prepared by the nucleophilic substitution reaction of the sulphinite anion on haloalkanes. In the absence of a phase-transfer catalyst, the reaction times are generally long and the yields are low, and undesirable O-alkylation of the sulphinite anion competes with S-alkylation. The stoichiometric reaction of the preformed tetra-n-butylammonium salt of 4-toluenesulphinic acid with haloalkanes produces 4-tolyl sulphones in high yield [1], but it has been demonstrated that equally good... 

Spurred by our desire to avoid use of expensive dipolau aprotic solvents in nucleophilic aromatic substitution reactions, we have developed two alternative phase transfer systems, which operate in non-polar solvents such as toluene, chlorobenzene, or dichlorobenzene. Poleu polymers such as PEG are Inexpensive and stable, albeit somewhat inefficient PTC agents for these reactions. N-Alkyl-N, N -Dialkylaminopyridinium salts have been identified as very efficient PTC agents, which are about 100 times more stable to nucleophiles than Bu NBr. The bis-pyridinium salts of this family of catalysts are extremely effective for phase transfer of dianions such as bis-phenolates. 

An alternative possibihty for catalyst recychng by a phase separation is the use of phase transfer catalysts in a biphasic reaction, hi the telomerization of... 

Alternative routes for the multi-step preparation of 6-p F]fluoro-L-DOPA (given here as an example and also applicable to other amino acids) include the use of enantioselective benzylations using either a chiral auxiliary [Scheme 45, Pathway B (i) (ii) (iv) (viii)] [207-209] or a chiral phase transfer catalyst [Scheme 45, Pathway C (i) (ii) (v) (viii)] [210-212], The latter approach, avoiding the use of dry reagents, is well suited to automation and enables the production of more than 200 mCi (7.4 GBq) of 6-p F]fluoro-L-DOPA from 1.5 Ci (55.5 GBq) of starting [ F]fluoride [213]. 

The inefficiency of the platinum/hydrogen reduction system and the dangers involved with the combination of molecular oxygen and molecular hydrogen led to a search for alternatives for the reduction of the manganese porphyrin. It was, for example, found that a rhodium complex in combination with formate ions could be used as a reductant and, at the same time, as a phase-transfer catalyst in a biphasic system, with the formate ions dissolved in the aqueous layer and the manganese porphyrin and the alkene substrate in the organic layer [28]. 

An important alternative to the Ullmann method is the use of certain nickel complexes,193 This method has also been used intramolecularly.194 Aryl halides ArX can also be converted to Ar—Ar195 by treatment with activated Ni metal,196 with Zn and nickel complexes,197 with aqueous alkaline sodium formate, Pd-C, and a phase transfer catalyst,l9li and in an electrochemical process catalyzed by a nickel complex,199... 

The Maruoka group recently reported an alternative concept based on a one-pot double alkylation of the aldimine of glycine butyl ester, 44a, in the presence of the chiral ammonium salt 29 as chiral phase-transfer catalyst (the principal concept of this reaction is illustrated in Scheme 3.18, route 2) [58], Under optimized reaction conditions products of type 43 were obtained in yields of up to 80% and with high enantioselectivity (up to 98% ee). A selected example is shown in Scheme 3.20. 

In the phase-transfer processes discussed in Section 11.2 it is assumed that the anionic hydride source, i.e. borohydride or a hypervalent hydrosilicate, forms an ion-pair with the chiral cationic phase-transfer catalyst. As a consequence, hydride transfer becomes enantioselective. An alternative is that the nucleophilic activator needed to effect hydride transfer from a hydrosilane can act as the chiral inducer itself (Scheme 11.6). 

Use of a microemulsion to overcome reagent incompatibility can be seen as an alternative to the more conventional approach of carrying out the reaction in a two-phase system with the use of a phase transfer catalyst. The latter is usually either a quaternary ammonium salt or a crown ether. There are several examples in the literature of comparisons between the microemulsion concept and phase transfer catalysis. The topic has also recently been reviewed [46]. 

The use of a two-phase system with added phase transfer catalyst and the use of a microemulsion are two alternative approaches to overcome reagent incompatibility problems in organic synthesis. Both routes have proved useful but on entirely different accounts. In phase transfer catalysis the nucleophilic reagent is carried into the organic phase where it becomes highly reactive. In the microemulsion approach there is no transfer of reagent from one environment to another the success of the method relies on the very large oil-water interface at which the reaction occurs. 

This review shows that microemulsions are of interest as media for organic reactions on several accounts. First of all they can be used as a means to overcome reagent incompatibility, which frequently occurs between a lipophilic organic compound and an inorganic salt. Used for this purpose they can be regarded as an alternative to the use of a two-phase system with added phase transfer catalyst. The concept of a micro emulsion medium and phase transfer catalysis can also be combined to give a system of very high reactivity. 

An alternative method for preparing 1-alkylisatins consists in the reaction of isatin and alkyl halides in a benzene-chloroform/50% aq. KOH biphasic system, employing tetrabutylammonium hydrogensulfate as the phase transfer catalyst. ... 

In aqueous media the highest yields of alkanediols are obtained using potassium permanganate in very basic solutions". Alternatively, in the presence of phase transfer catalysts such as quaternary ammonium and phosphonium salts100, dimethyl polyethylene glycols101, or crown ethers 102 (Table 10), solvation of the permanganate ion in apolar organic media is also possible ... 

Alternative base/solvent couples can be selected among DABCO/DMF [27], Na0H/K2C03/DMF/PTC (phase transfer catalyst), KOH/MeOH [28], DMAP/ NEts/DMTCl [29] and quinoline [30,31]. For optimal results, the choice of the most appropriate couple depends on solubility and acidity issues. The yields are usually from good to excellent, the only exceptions arising when the phenol is excessively hindered or additional acidic protons are present in the molecule. 

MeTHF has also been used as an alternative to dichloromethane in biphasic reactions including alkylations, amidations and nucleophilic substitutions. For example, 2-nitrophenyl phenyl ether was prepared in 95% yield using 2-MeTHF as the organic solvent through reaction of phenol and o-fluoronitrobenzene using tetrabutylammonium bromide as a phase transfer catalyst. 

A MW-assisted protocol for the synthesis of azides, thiocyanates, and sulfones has been developed (Scheme 12) that has proved to be a useful alternative, as the use of environmentally deterimental volatile chlorinated hydrocarbons is avoided.All the reactions with these readily available halides or tosylates have shown significant increase in reactivity, thus reducing the reaction times with substantial improvement in the yields. Various functional groups such as ester, carboxylic acid, carbonyl, and hydroxyl were unaffected under the mild reaction conditions employed. This method involves simple experimental procedures and product isolation which avoids the use of phase-transfer catalysts, and is expected to contribute to the development of greener strategy for the preparation of various azides, thiocyanates, sulfones, and other useful compounds. 

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