Quaternary ammonium salts as phase-transfer catalysts

The early work by CM Starks at the Continental Oil Co., Ponca City, USA showed the versatility of quaternary ammonium salts as phase-transfer catalysts in organic synthesis. 

For reviews of the asymmetric synthesis of amino acids using quaternary ammonium salts as phase-transfer catalysts, see ... 

Starks, C. M., Quaternary Ammonium Salts as Phase Transfer Catalysts, in Industrial Applications of Surfactants II, Karsa, ed., Roy. Soc. of Chemistry, Canibridge, p. 165 (1990). 

The term phase-transfer catalysis was introduced in 1971 by Starks, explaining the critical role of tetraalkylammonium or phosphonium salts to promote reactions between two substances located in different immiscible phases (325). Over the years, the use of achiral quaternary ammonium salts as phase-transfer catalysts (PTCs) has attracted widespread interest not only in academia but also for industrial applications (326, 327). Some of the most important benefits of phase-transfer catalysis are simple experimental conditions, which are usually easily scalable, in addition to mild reaction conditions, and the use of inexpensive and environmentally friendly reagents and solvents. 

A major achievement was the discovery that the Heck reactions are greatly accelerated in the presence of quaternary ammonium salts as phase-transfer catalysts and solid bases (the Jeffery conditions Pd(OAc)2, MHCOj (M = K, Na), nBu4NX (X = Br, Cl), DMSO, or DMF) [197j. Under these conditions, iodoarenes and iodoalkenes can be coupled to alkenes at room temperature. The major role of the tetraalkylammonium salts apparently lies in enhancing the regeneration of the zerovalent palladium catalyst [223]. 

In conclusion, polycondenaation of BPA with DCB in aqueous alkali-toluene system, at 65 C, using a quaternary ammonium salt as phase transfer catalyst leads to polyethers having chloromethyl groups at each end, in excellent yields. Molecular weights distribution of these polyethers is surprisingly quite narrow (see Table 2), Additional studies with this and other polymer systems are in progress. 

In contrast to the broad synthetic utility of chiral quaternary ammonium salts in PTC, the application of chiral quaternary phosphonium salts as phase-transfer catalysts remains poorly studied, and only a few special examples have been reported so far with limited success. In 1998, Manabe prepared the chiral phosphonium salt... 

Quaternary ammonium salts as we have seen are useful m synthetic organic chem istry as phase transfer catalysts In another more direct application quaternary ammo mum hydroxides are used as substrates m an elimination reaction to form alkenes... 

Another catalytic system which has been successfully applied to the autoxidation of substituted toluenes involves the combination of Co/Br" with a quaternary ammonium salt as a phase transfer catalyst (ref. 20). For example, cobalt(II) chloride in combination with certain tetraalkylammonium bromides or tetraalkylphosphonium bromides afforded benzoic acid in 92 % yield from toluene at 135-160 °C and 15 bar (Fig. 19). It should be noted that this system does not require the use of acetic acid as solvent. The function of the phase transfer catalyst is presumably to solubilize the cobalt in the ArCH3 solvent via the formation of Q + [CoBr]. ... 

Arai et al.51 reported that by using a catalytic amount of chiral quaternary ammonium salt as a phase transfer catalyst, a catalytic cycle was established in asymmetric HWE reactions in the presence of an inorganic base. Although catalytic turnover and enantiomeric excess for this reaction are not high, this is one of the first cases of an asymmetric HWE reaction proceeding in a catalytic manner (Scheme 8-20). 

The following quaternary ammonium salts are used as phase transfer catalyst tetra-K-butylammonium chloride (TBAC), tetra-n-butylammonium bromide (TBAB), benzyltriethylammonium chloride (BTEAC), and benzyltriethylammo-nium bromide (BTEAB). Chlorinated hydrocarbons, such as dichloromethane (DCM), chloroform (CF), tetrachloromethane (TCM), 1,2-dichloromethane (DCE), and nitrobenzene (NB) are used as solvents. The effects of phase-transfer catalyst and solvent on the yield and reduced viscosity are summarized in Table 9.1. 

Onium salts, crown ethers, alkali metal salts or similar chelated salts, quaternary ammonium and phosphonium are some of the salts which have been widely used as phase transfer catalysts (PTC). The choice of phase transfer catalysts depends on a number of process factors, such as reaction system, solvent, temperature, removal and recovery of catalyst, base strength etc. 

A number of organic molecules capable of efficiently operating as phase-transfer catalysts is now available. The reaction mechanism both for soluble and polymer-supported systems is completely understood and the factors ruling the reactivity are recognised. The drawback of soluble catalysts is their difficult separation from the reaction products which in the case of the expensive macropolycyclic ligands imposes severe limitations in their use on a large scale. The cheap and easy to synthesize ammonium quaternary salts, providing they are stable under the reaction conditions, represent the catalysts of choice. 

Polymer phase-transfer catalysts (also referred to as triphase catalysts) are useful in bringing about reaction between a water-soluble reactant and a water-insoluble reactant [Akelah and Sherrington, 1983 Ford and Tomoi, 1984 Regen, 1979 Tomoi and Ford, 1988], Polymer phase transfer catalysts (usually insoluble) act as the meeting place for two immiscible reactants. For example, the reaction between sodium cyanide (aqueous phase) and 1-bromooctane (organic phase) proceeds at an accelerated rate in the presence of polymeric quaternary ammonium salts such as XXXIX [Regen, 1975, 1976]. Besides the ammonium salts, polymeric phosphonium salts, crown ethers and cryptates, polyethylene oxide), and quaternized polyethylenimine have been studied as phase-transfer catalysts [Hirao et al., 1978 Ishiwatari et al., 1980 Molinari et al., 1977 Tundo, 1978]. 

Heterocyclic amines have also been used as phase transfer catalysts. However, because these amines quaternize easily, the question is whether the operative catalyst is the tertiary amine or the quaternary ammonium salt formed in situ Furukawa et al.286 have shown that a methyl 2-pyridyl sulfoxide may be used as a phase transfer catalyst and promote substitution reactions between lithium chloride or sodium cyanide and benzyl bromide. According to the authors, the catalyst behaves as a cation complexer and not as a quaternary ammonium salt formed in situ by a Menschutkin reaction. 

Rozwadowska and coworkers carried out the asymmetric alkylation of isoquino-line Reissert compounds under phase-transfer conditions using cinchonine-derived quaternary ammonium salts as catalysts. The best enantioselectivity was achieved in the benzylation and allylation of 1 -cyano-2-phenoxy carbonyl-1,2-dihydroisoquinoline (17) catalyzed by 2a (Scheme 2.14) [34]. 

The first example of a catalytic asymmetric Horner-Wadsworth-Emmons reaction was recently reported by Arai et al. [78]. It is based on the use of a chiral quaternary ammonium salt as a phase-transfer catalyst, 78, derived from cinchonine. Catalytic amounts (20 mol%) of organocatalyst 78 were initially used in the Homer-Wadsworth-Emmons reaction of ketone 75a with a variety of phospho-nates as a model reaction. The condensation products of type 77 were obtained in widely varying yields (from 15 to 89%) and the enantioselectivity of the product was low to moderate (< 43%). Although yields were usually low for methyl and ethyl phosphonates the best enantioselectivity was observed for these substrates (43 and 38% ee, respectively). In contrast higher yields were obtained with phosphonates with sterically more demanding ester groups, e.g. tert-butyl, but ee values were much lower. An overview of this reaction and the effect of the ester functionality is given in Scheme 13.40. 

This reaction can be conducted under solid-hquid phase transfer catalytic (PTC) conditions using sohd potassium carbonate as base and a liquid lipophihc quaternary ammonium salt as catalyst. Numerous carbodiimides with a side chain bearing a tertiary amino group, such as-(CH2) NMe2, are obtained in this manner. Sheehan and cowoikers used a modification of this procedure to synthesize several water soluble carbodiimides. ... 

Arenediazo cyanides. Arenediazonium tetrafluoroborates react with solid KCN and 18-crown-6 (0.05 equiv.) in CH2CI2 to give arenediazo cyanides in 75-95% yield. In the absence of 18-crown-6, only low yields of the arenediazo cyanides are obtained after prolonged reaction times. Quaternary ammonium salts are not useful as phase-transfer catalysts. Arenediazo cyanides undergo various reactions, including the Diels-Alder cycloaddition. ... 

The Darzens reaction (tandem aldol-intramolecular cyclization sequence reaction) is a powerful complementary approach to epoxidation (see Chapter 5) that can be used for the synthesis of a,P-epoxy carbonyl and a,p-epoxysulfonyl compounds (Scheme 8.32). Currently, all catalytic asymmetric variants of the Darzens reactions are based on chiral phase-transfer catalysis using quaternary ammonium salts as catalysts. 

Asymmetric Michael additions can also be performed under phase-transfer conditions with an achiral base in the presence of a chiral quaternary ammonium salt as a phase-transfer agent. Conn and coworkers conducted the Michael addition of 2-propyl-l-indanone (13) to methyl vinyl ketone under biphasic conditions (aq 50% NaOH/toluene) using the cinchonine/cinchonidine-derived chiral phase-transfer catalysts (PTCs), 14a and 14b, as a catalyst (Scheme 9.5). However, only low to... 

Other methods are also available for the generation of dichlorocarbene which, in the presence of alkenes, forms 1,1-dichlorocyclopropanes, e.g. reaction of chloroform with oxirane, using a quaternary ammonium salt as the catalyst and an alkene (Houben-Weyl, Vol. 4/3, pp 374-381 and Vol. E19b, p 1530).The discovery of new, more convenient and equally efficient methods (especially phase-transfer catalysis) means that older approaches are unused at present. 

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