Catalysts chiral ammonium salt phase

Arai and co-workers have used chiral ammonium salts 89 and 90 (Scheme 1.25) derived from cinchona alkaloids as phase-transfer catalysts for asymmetric Dar-zens reactions (Table 1.12). They obtained moderate enantioselectivities for the addition of cyclic 92 (Entries 4—6) [43] and acyclic 91 (Entries 1-3) chloroketones [44] to a range of alkyl and aromatic aldehydes [45] and also obtained moderate selectivities on treatment of chlorosulfone 93 with aromatic aldehydes (Entries 7-9) [46, 47]. Treatment of chlorosulfone 93 with ketones resulted in low enantioselectivities. 

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. 

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. 

The enantio-determining step of nucleophilic additions to a-bromo-a,y -unsaturated ketones is mechanistically similar to those of nucleophilic epoxidations of enones, and asymmetry has also been induced in these processes using chiral phase-transfer catalysts [20]. The addition of the enolate of benzyl a-cyanoacetate to the enone 31, catalysed by the chiral ammonium salt 32, was highly diastereoselective and gave the cyclopropane 33 in 83% ee (Scheme 12). Good enantiomeric excesses have also been observed in reactions involving the anions of nitromethane and an a-cyanosulfone [20]. 

The advantages of PTC reactions are moderate reaction conditions, practically no formation of by-products, a simple work-up procedure (the organic product is exclusively found in the organic phase), and the use of inexpensive solvents without a need for anhydrous reaction conditions. PTC reactions have been widely adopted, including in industrial processes, for substitution, displacement, condensation, oxidation and reduction, as well as polymerization reactions. The application of chiral ammonium salts such as A-(9-anthracenylmethyl)cinchonium and -cinchonidinium salts as PT catalysts even allows enantioselective alkylation reactions with ee values up to 80-90% see reference [883] for a review. Crown ethers, cryptands, and polyethylene glycol (PEG) dialkyl ethers have also been used as PT catalysts, particularly for solid-liquid PTC reactions cf. Eqs. (5-127) to (5-130) in Section 5.5.4. 

The asymmetric synthesis of a-alkyl-a-amino acids using a chiral catalyst is a useful method for the preparation of both natural and unnatural amino acids. O Donnell et al. developed the cinchona alkaloid-catalyzed alkylation of glycine derivatives [49]. However, almost all of the chiral phase-transfer catalysts were restricted to cinchona alkaloid derivatives. In 1999, Maruoka and co-workers designed a chiral ammonium salt bearing a binaphthyl backbone as a chiral phase-transfer catalyst (10a) (Figure 10.11), and demonstrated its catalytic activity... 

Optically active a, -epoxy stdfones. - The Darzens reaction of ethyl methyl ketone with chloromethyl / -tolyl sulfone in a two-phase system in the presence of chiral ammonium salts such as N-ethylephedrinium bromide results in a,/3-epoxy sulfones with 0-2.57o optical yields. However, if the supported catalyst (1) is used, optical yields of up to 23% can be obtained as in the example formulated in equation (I). On the other hand, the reaction is slower when the catalyst is supported. The presence of a hydroxy group jS to the nitrogen atom of the catalyst is essential for asymmetric induction. 

The enantioselective ester syntheses from acid salts, chlorides and anhydrides with racemic alkyl halides, catalysed by optically active polyaminesalmost certainly proceed via in situ formation of chiral ammonium salts, and therefore fall within the scope of phase transfer catalysts. Though the optical yields obtained are low, the work is important because it explores the use of polyamine species with a potential chirality derived from the polymerization of optically active oxazolines, and as such is again a novel approach. 

Although the term phase-transfer catalysis was introduced in 1971 by Starks [104], this field has received particular attention in recent decades. The use of chiral ammonium salts as catalysts (Figure 44.11) has been recognized as an effective tool for organic synthesis and much time has been spent in both industrial and academic sectors, making possible the development of munerous highly enanti-oselective processes [105]. The appHcabUity of phase-transfer catalysis (PTC) has... 

The asymmetric epoxidation of the chalcone type of substrate has also been accomplished using other types of chiral catalysts [15]. Wynberg was the first to use chiral ammonium salts, and obtained chalcone oxide with 55% ee using alkaline hydrogen peroxide as the stoichiometric oxidant and a quinine-derived quaternary ammonium salt as the chiral phase transfer catalyst [16]. More recently, Lygo... 

Besides the use of chiral ammonium salts as phase transfer catalyst, different azacrown ethers 51a-e derived from different sugars has been proposed as an alternative [52], For all systems the influence of the length of the chain on nitrogen atom was evaluated. For compounds 51a, b (glucose derivatives) the best results were obtained when was 2-hydroxyethyl. Whereas for compounds 51c-e, the best results were obtained for the corresponding 3-hydroxypropyl derivative. In neither case the enantiomeric excess was higher than 74%. 

Figure 12.8 Maruoka s chiral N-spiro binaphthyl-modified quaternary ammonium salt phase-transfer catalysts.

In the following example, although the synthesis of the azoniaspirocycle does not involve an acyclic compound, the reaction itself is very similar to those described in this section, hence its inclusion here (Equation 34). Maruoka and co-workers have designed a C2-symmetric chiral quarternary ammonium salt, which is then employed as a phase-transfer catalyst in an enantioselective alkylation <1999JA6519, 2001JFC(112)95, 2004TA1243>. 

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). 

Cinchona alkaloids now occupy the central position in designing the chiral non-racemic phase transfer catalysts because they have various functional groups easily derivatized and are commercially available with cheap price. The quaternary ammonium salts derived from cinchona alkaloids as well as some other phase transfer catalysts are... 

The first practical and efficient asymmetric alkylation by use of chiral phase-transfer catalysts was the alkylation of the phenylindanone 15 (R1=Ph), reported by the Merck research group in 1984.114-161 By use of the quaternary ammonium salt 7 (R=4-CF3i X=Br) derived from cinchonine, the alkylated products 16 were obtained in excellent yield with high enantiomeric excess, as shown in... 

The ammonium catalyst can also influence the reaction path and higher yields of the desired product may result, as the side reactions are eliminated. In some cases, the structure of the quaternary ammonium cation may control the product ratio with potentially tautomeric systems as, for example, with the alkylation of 2-naph-thol under basic conditions. The use of tetramethylammonium bromide leads to predominant C-alkylation at the 1-position, as a result of the strong ion-pair binding of the hard quaternary ammonium cation with the hard oxy anion, whereas with the more bulky tetra-n-butylammonium bromide O-alkylation occurs, as the binding between the cation and the oxygen centre is weaker [11], Similar effects have been observed in the alkylation of methylene ketones [e.g. 12, 13]. The stereochemistry of the Darzen s reaction and of the base-initiated formation of cyclopropanes under two-phase conditions is influenced by the presence or absence of quaternary ammonium salts [e.g. 14], whereas chiral quaternary ammonium salts are capable of influencing the enantioselectivity of several nucleophilic reactions (Chapter 12). 

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