Quaternary ammonium salts as phase-transfer

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. 

Some other very important events in the historic development of asymmetric organocatalysis appeared between 1980 and the late 1990s, such as the development of the enantioselective alkylation of enolates using cinchona-alkaloid-based quaternary ammonium salts under phase-transfer conditions or the use of chiral Bronsted acids by Inoue or Jacobsen for the asymmetric hydro-cyanation of aldehydes and imines respectively. These initial reports acted as the launching point for a very rich chemistry that was extensively developed in the following years, such as the enantioselective catalysis by H-bonding activation or the asymmetric phase-transfer catalysis. The same would apply to the development of enantioselective versions of the Morita-Baylis-Hillman reaction,to the use of polyamino acids for the epoxidation of enones, also known as the Julia epoxidation or to the chemistry by Denmark in the phosphor-amide-catalyzed aldol reaction. ... 

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). 

Rasmussen and co-workers. Chapter 10, have shown that many free-radical polymerizations can be conducted in two-phase systems using potassium persulfate and either crown ethers or quaternary ammonium salts as initiators. When transferred to the organic phase persulfate performs far more efficiently as an initiator than conventional materials such as azobisisobutyronitrile or benzoyl peroxide. In vinyl polymerizations using PTC-persulfate initiation one can exercise precise control over reaction rates, even at low temperatures. Mechanistic aspects of these complicated systems have been worked out for this highly useful and economical method of initiation of free-radical polymerizations. 

Polymerization of butyl acrylate was also studied by us in ethyl acetate/water two phase systems (3) using potassium persulfate/quaternary ammonium salts as the initiator system. Under these conditions (a minimum amount of water was used to dissolve the persulfate), it was found that symmetrical quat salts were more efficient than surfactant type quat salts. Also, the more lipophilic quat salts were more efficient. These results prompted us to propose formation of an organic-soluble quaternary ammonium persulfate via typical phase transfer processes. 

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. ... 

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. 

A new route to optically active trialkylphosphine oxides, and hence phosphines, has been reported. The key step, the conversion of the optically active phos-phinite (4) to phosphine oxide, is extremely sensitive to the solvent mixture used, and even under the most favourable conditions involves considerable racemization. Small levels of optical activity (0—8 % enantiomeric excess) have been induced in the phosphine oxide product by hydrolysis of the phosphonium salt (5) under phase-transfer conditions using optically active quaternary ammonium salts as chiral catalysts. ... 

The epoxidation of conjugated double bonds also proceeds smoothly with the Oxone-acetone system, as illustrated by eq 9. The conversion of water-insoluble enones can be accomplished with this method using CH2CI2 as a cosolvent and a quaternary ammonium salt as a phase-transfer catalyst. However, a more convenient procedure utilizes 2-butanone both as a dioxirane precursor and as an immiscible cosolvent (eq 10). No phase-transfer agent is required in this case. 

Quaternary ammonium salts, compounds of the type R4N X , find application as phase-transfer catalysts. A small amount of a quaternary ammonium salt promotes the transfer of an anion from aqueous solution, where it is highly solvated, to an organic solvent, where it is much less solvated and much more reactive. 

The use of ot,p-unsaturated aldehydes as Michael acceptors always represents a challenging situation because of the tendency of enals to undergo 1,2- rather than the desired 1,4- addition reaction. Moreover, working under phase-transfer catalysis conditions incorporates an additional element of difficulty, because of the propensity of enolizable enals to undergo self-condensation side reactions. For this reason, there are only a few examples reporting enantioselective Michael reactions with ot,p-unsaturated aldehydes as Michael acceptors under PTC conditions, both coming from the Maruoka research team and also both making use of chiral tV-spiro quaternary ammonium salts as catalysts. 

The principle of extraction method used to separate PTC and product is based on solubility of quaternary ammonium salt in alkaline aqueous solution. " For example, tetrabutylammonium bromide is soluble to the extent of 27% in dilute (1% NaOH) aqueous solutions, but when the solution is made more concentrated (15% NaOH), the solubility of Bu4N Br decreases to 0.07%. When the products are obtained in PTC system, they can be usually separated from PTC by distillation method. PTC catalyst in the distillation residue may sometimes be reusable. With quaternary ammonium salts as catalysts, temperatures above 100-120 C usually result in partial or total decomposition of the quaternary salts to trialkylamines and other products. Mieczynska et al. and Monflier et al. investigated the hydrogenation and hydroformylation under phase transfer catalytic conditions. They found that the yield of aldehydes obtained in hydroformylation of 1-hexene strongly depends on solvent 24% in toluene, 53-86% in toluene-water-ethanol mixture and 77-94% in water-ethanol solution. The mixture of water-ethanol as a solvent was also found to be the best for hydrogenation of 1-hexene (96% of hexane). Conversion of Ph2PCH(CH3)(COOH) phosphine into sodium salt Ph2PCH(CH3)(COONa) yields aldehyde in toluene, 92% in toluene-water and 94% in toluene-water-ethanol mixture. 

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