Phase-transfer catalysis conditions quaternary ammonium salt

A biphenyl and ct-methylnaphthylamine-derived chiral quaternary ammonium salt 23d, which was shown by Lygo to be effective for the asymmetric alkylation of Schiffs base 20, was also effective in the Michael reaction (Scheme 7.12) [43]. Notably, the enantioselectivity was highly dependent on the reaction conditions and substrates used. The Michael reaction of imine esters such as benzhydryl and benzyl esters with a,p-unsaturated ketones under solid-liquid phase-transfer catalysis conditions afforded the Michael adduct in up to 94% ee and 91% ee, respectively, while the tert-butyl ester showed moderate enantioselectivity (Scheme 7.12). Interestingly, in contrast to earlier reports, acrylate [42] and acrylamides failed to undergo the Michael reaction under these optimized conditions. 

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 best results were obtained by using a quaternary ammonium salt like TBAH as catalyst under phase-transfer-catalysis conditions. 

The application of phase-transfer catalysis to the Williamson synthesis of ethers has been exploited widely and is far superior to any classical method for the synthesis of aliphatic ethers. Probably the first example of the use of a quaternary ammonium salt to promote a nucleophilic substitution reaction is the formation of a benzyl ether using a stoichiometric amount of tetraethylammonium hydroxide [1]. Starks mentions the potential value of the quaternary ammonium catalyst for Williamson synthesis of ethers [2] and its versatility in the synthesis of methyl ethers and other alkyl ethers was soon established [3-5]. The procedure has considerable advantages over the classical Williamson synthesis both in reaction time and yields and is certainly more convenient than the use of diazomethane for the preparation of methyl ethers. Under liquidrliquid two-phase conditions, tertiary and secondary alcohols react less readily than do primary alcohols, and secondary alkyl halides tend to be ineffective. However, reactions which one might expect to be sterically inhibited are successful under phase-transfer catalytic conditions [e.g. 6]. Microwave irradiation and solidrliquid phase-transfer catalytic conditions reduce reaction times considerably [7]. 

The general concept of phase transfer catalysis applies to the transfer of any species from one phase to another (not just anions as illustrated above), provided a suitable catalyst can be chosen, and provided suitable phase compositions and reaction conditions are used. Most published work using PTC deals only with the transfer of anionic reactants using either quaternary ammonium or phosphonium salts, or with crown ethers in liquid-liquid or liquid-solid systems. Examples of the transfer and reaction of other chemical species have been reported(24) but clearly some of the most innovative work in this area has been done by Alper and his co-workers, as described in Chapter 2. He illustrates that gas-liquid-liquid transfers with complex catalyst systems provide methods for catalytic hydrogenations with gaseous hydrogen. 

Undoubtedly the most important and widely used procedure for the generation of dichlorocarbene involves the reaction of chloroform with aqueous sodium hydroxide under the conditions of phase transfer catalysis (PTC), introduced by Makosza.20-22 Under these conditions chloroform reacts with sodium hydroxide to form sodium trichloromethylide which on exchange with a quaternary ammonium salt, usually benzyltriethylammonium chloride, is converted to the unstable quaternary ammonium methylide which dissociates in the organic phase to give dichlorocarbene. The dichlorocarbene irreversibly adds to the alkene (Scheme 1). 

For the glycosylation of phenols with glycosyl halides, phase-transfer conditions using aqueous sodium or potassium hydroxide and quaternary ammonium salts have also been reported [89-94]. By using phase-transfer catalysis, a method for solid-phase synthesis of aryl glycosides was developed [95]. 

Phase transfer catalysis and the use of crown ethers are also of particular advantage in alkanenitrile synthesis (Table 1). Usually quaternary ammonium and phosphonium salts serve quite well as catalysts. Another modification is represented by the use of a solid catalyst, which is insoluble in the two-phase system, for instance alumina or anion-exchange resins (triphase catalysis). Crown ethers again capture the cations and generate naked cyanide ions in fairly nonpolar solvents, leading to exceptionally mild reaction conditions. 

The asymmetric alkylation of glycine derivatives is one of the most simple methods by which to obtain optically active a-amino acids [31]. The enantioselective alkylation of glycine Schiff base 52 under phase-transfer catalysis (PTC) conditions and catalyzed by a quaternary cinchona alkaloid, as pioneered by O Donnell [32], allowed impressive degrees of enantioselection to be achieved using only a very simple procedure. Some examples of polymer-supported cinchona alkaloids are shown in Scheme 3.14. Polymer-supported chiral quaternary ammonium salts 48 have been easily prepared from crosslinked chloromethylated polystyrene (Merrifield resin) with an excess of cinchona alkaloid in refluxing toluene [33]. The use of these polymer-supported quaternary ammonium salts allowed high enantioselectivities (up to 90% ee) to be obtained. 

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. ... 

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. 

Phenols have been phosphorylated under phase transfer conditions in the presence of a nucleophilic catalyst [31, 32]. The reaction of 4-nitrophenol with dimeth-oxythiophosphoryl chloride is ordinarily slow and leads to a mixture of the desired methyl parathion and hydrolysis products. Addition of N-methylimidazole enhanced the rate but the best results were obtained when both the imidazole and a quaternary ammonium salt (TBAB) were used at the same time. The co-catalysis was accounted for in terms of nucleophilic activation of the acylating agent by imidazole and solubilization of the phenoxide by ion pairing with the quaternary ion. The overall transformation is formulated in equation 6.13. 

Another methodology that shows great promise for selective reductions is Phase Transfer Catalysis (PTC) under one atmosphere of H2. Under very gentle conditions, with a quaternary ammonium salt as the PT agent, 1 mol % of [RhCl(l,5-hexadiene]2 catalyzes the reduction of aromatic rings yields vary to some extent with the phase transfer agent [31]. 

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