Ammonium salts, chiral structures

E. J. Corey, F. Xu, M. C. Noe, A Rational Approach to Catalytic Enantioselective Enolate Alkylation Using a Structurally Rigidified and Defined Chiral Quaternary Ammonium Salt under Phase Transfer Conditions , J. Am. Chem. Soc, 1997,119,12414-12415. 

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). 

Attachment of bulky chiral barriers to achieve enantiomeric selection is exemplified by ligands (61),204 (63)69 and (64).19 Ligands of type (61) are especially efficient chiral compounds with binap-thyl hinges . The orientation of the binaphthyl rings for (61) is shown more explicitly in (62).234 With optically pure (61), complete enantiomeric separation of ammonium salt racemates such as (67) is obtained.235-237 The structure has been determined crystallographically for the less stable d form of the PF6- salt of (67) with the (S,S) host (61). The results indicate that the receptor, substrate, counterion and solvent have undergone several steric concessions in order to relieve the strain imposed on the system by the visit of an unwanted guest.238... 

As reviewed in this chapter, cinchona alkaloids have played a crucial role in the development of asymmetric phase-transfer catalysis since its advent, and today constitute a privileged structural motif that may be widely utilized for the design of new chiral quaternary ammonium salts. These benefits are due not only to the... 

In 1999, in consideration of the readily structural modifications and fine-tuning of catalysts to attain sufficient reactivity and selectivity, Maruoka and coworkers designed and prepared the structurally rigid, chiral spiro ammonium salts of type 1 derived from commercially available (S)- or (R)-1,1 -bi-2-naphthol as a new C2-symmetric chiral phase-transfer catalyst, and successfully applied this to the highly efficient, catalytic enantioselective alkylation of N-(diphenylmethylene)glycine tert-butyl ester under mild phase-transfer conditions (Scheme 5.1) [7]. 

Maruoka and coworkers also investigated the substantial reactivity enhancement of N-spiro chiral quaternary ammonium salt and simplification of its structure, the aim being to establish a truly practical method for the asymmetric synthesis of a-amino acids and their derivatives. As ultrasonic irradiation produces homogenization (i.e., very fine emulsions), it greatly increases the reactive interfacial area, which may in turn deliver a substantial rate acceleration in the liquid-liquid phase-transfer reactions. Indeed, sonication of the reaction mixture of 2, methyl iodide and (S,S)-lc (1 mol%) in toluene-50% KOH aqueous solution at 0 °C for 1 h gave rise to the corresponding alkylation product in 63% yield with 88% ee. Hence, the reaction was speeded up markedly, and the chemical yield and enantioselectivity were comparable with those of the reaction with simple stirring (0°C for 8h 64%, 90% ee) (Scheme 5.5) [10]. 

Fig. 4.1 The structurally rigid, chiral spiro ammonium salts.

The chiral 18-crown-6 derivative 1 (Scheme 4.1), and similar structures derived from it, are capable of exhibiting enantiomeric differentiation in the complexation of racemic primary ammonium salts. Compound ll-1 has been... 

Sulfonium salts (20) have a non-planar tetrahedral configuration, and consequently the structure is chiral when all the attached groups, namely R, R and R", are different. Such sulfonium salts can generally be resolved into quite stable optical isomers (see Chapter 6, p. 83). Sulfonium salts are analogous to quaternary ammonium salts and the hydroxides are strong bases which behave similarly on heating (cf. the Hofmann elimination of quaternary ammonium hydroxides). 

More recently, Feng and coworkers [62] realized that the enantioselective cyano-formylation of aromatic aldehydes with ethyl cyanoformate, using a chiral quaternary ammonium salt and triethylamine. However, despite their optimization studies on the catalyst structure and reaction conditions, only moderate ee values (up to 72% ee) were obtained. 

The careful engineering of suitable host structures has already led to new methods for separations of, for example, metal cations (17) or of chiral ammonium salts (2). 

Excellent results were also reported recently by Maruoka and coworkers by using 50% aqueous NaOH in toluene and a (5)-BINAP-derived C2-symmetric ammonium catalyst 14 [64]. The steric and/or electronic properties of this new class of catalysts can be finely tuned in order to improve reactivity and enantioselectivity. The N-spiro structure along with their high lipophilicity make such catalysts much more reactive than the traditional PTC catalysts, e.g., Bu4N+Br, in otherwise identical conditions [65]. Excellent ees are usually obtained in short reaction times with 1 % of catalyst only moreover, they should be more stable under basic conditions than ammonium salt derived from Cinchona alkaloids since they do not undergo Hofmann elimination resulting from lack of yS-hydrogens. However, they are not as easily prepared as Cinchona ammonium catalysts and are expected to be quite expensive since they are not derived from the chiral pool. On... 

---