Chiral organic salts

Figure 4. General scheme for the synthesis of chiral organic salts.

The use of salt formation to expand the number of crystals which contain a single molecular type was first applied by Meredith (26), and more recently by Marder et. al. (22). In the latter work, ionic interactions are used to offset dipolar interactions among achiral molecules, which enhances the probability that the resulting crystal will be noncentrosymmetric. In our case, of course, noncentrosymmetry is ensured by the chirality of the molecules involved. It is important to note that, within the picture we have presented, neither the assurance of noncentrosymmetry, nor the enhanced hyperpolarizability of the chiral molecule guarantees that the nonlinearity of any particular chiral organic salt crystal will be large. These properties simply ensure that each crystal so formed has an equal opportunity to express the molecular hyperpolarizability in an optimized way. 

From this information, we have estimated(25) that between 0.5 and 1% of the chiral organic salts formed from amino acids and alpha-hydroxy acids have lower threshold powers than KDP for doubling or tripling 1.05 pm light. The probability P of finding such a crystal in a random sample of N crystals from the population of chiral organic salts is given by... 

The work described in this paper represents the contributions of several people. Laura Davis is responsible for the linear optical property measurements and the development of the microreffactometer. Most of the nonlinear optical measurements on small single crystals have been made by Mark Webb, who is also responsible for several improvements in the apparatus and technique. Francis Wang synthesized the chiral organic salts and did the powder SHG measurements. David Eimerl was the source of much encouragement, advice, and support during the course of this work. 

Experimental details solid-state photolysis 957 A crushed crystalline ketone (279a or 279b) ( 5 mg), suspended in hexane (3 ml), was placed between Pyrex microscope slides, sealed in a polyethylene bag under nitrogen and irradiated with a medium-pressure mercury lamp (450 W) at a distance of 10 cm from a water-cooled Pyrex immersion well (Figure 3.9) at either 20 or — 20 °C (cryostat ethanol bath). The product, a chiral organic salt, was derivatized to the corresponding methyl ester by treatment with excess diazomethane and purified by column chromatography. 

Even optically active PVKs can be prepared by using chiral organic salts [442]. 

Cheung, E., Kang, T., Netherton, M. R., Scheffer, J. R., and Trotter, J., Conformational enantiom-erism in chiral organic salts containing crystallographically independent anion-cation pairs, /. Am. Chem. Soc., 122,11753, 2000. 

Compound 72 was shown to display enantioselectivity in the extraction of chiral potassium salts from water into the organic phase.105 The supramolec-ular polymer possesses a homochiral helical architecture onto which one of the anionic enantiomers preferentially binds. Intriguingly, for some of the anions the octamer and polymer showed opposite selectivity, illustrating the difference in supramolecular chirality of the two systems. Furthermore, the polymer was capable of inducing a Cotton effect in the achiral compound potassium A-(2,4-dinitrophenyl)glycinate. Since the apolar side chains would... 

In the context of our work in the area of chiral nucleophilic carbenes and their utility in organic synthesis, we have developed a conceptually distinct approach to catalyzed acylation using a-haloaldehydes as acylation precursors. The use of a chiral triazolium salt in the presence of base allows an enantioselective desymme-trization of meio-hydrobenzoin to proceed in 83% ee and good yield ... 

Crown ethers bind well to organic ammonium cations and oxonium ions by charge-assisted hydrogen bonding interactions, as well as metal cations. In some cases they can be used to resolve chiral ammonium salts. 

The classic, chiral auxiliaries used in the optical resolution process were natural acidic or basic compounds, able to form crystalline organic salts preferentially... 

The above drawbacks of crystalline photoreactions are circumvented in an approach called the ionic auxiliary approach which is outlined below [185-207]. Scheffer and coworkers make a salt of a substrate having a carboxylic acid with a chiral organic amine or vice versa. The chirality of the amine would necessitate that the salt crystallize in a chiral space group. The crystal formed in this fashion would also be able to withstand higher conversions due to stronger lattice forces in these crystals. An example of this type of approach is shown in Scheme 8. Treatment of the dibenzobarralene derivative 18, with the tert-butyl ester of (S)-proline 19, afforded salt 20 irradiation of the crystals of this salt gave diester 21. In this reaction, only one regioisomer 21 is formed, and this product is formed in over 95% ee. More examples are to be found in Chap. 12. 

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. 

Upon treating certain (but not all) aromatic aldehydes or glyoxals (a-keto aldehydes) with cyanide ion (CN ), benzoins (a-hydroxy-ketones or acyloins) are produced in a reaction called the benzoin condensation. The reverse process is called the retro-benzoin condensation, and it is frequently used for the preparation of ketones. The condensation involves the addition of one molecule of aldehyde to the C=0 group of another. One of the aldehydes serves as the donor and the other serves as the acceptor. Some aldehydes can only be donors (e.g. p-dimethylaminobenzaldehyde) or acceptors, so they are not able to self-condense, while other aldehydes (benzaldehyde) can perform both functions and are capable of self-condensation. Certain thiazolium salts can also catalyze the reaction in the presence of a mild base. This version of the benzoin condensation is more synthetically useful than the original procedure because it works with enolizable and non-enolizable aldehydes and asymmetric catalysts may be used. Aliphatic aldehydes can also be used and mixtures of aliphatic and aromatic aldehydes give mixed benzoins. Recently, it was also shown that thiazolium-ion based organic ionic liquids (Oils) promote the benzoin condensation in the presence of small amounts of triethylamine. The stereoselective synthesis of benzoins has been achieved using chiral thiazolium salts as catalysts. 

Recently, Ni and group [66] introduced a new type of chiral ionic liquid based on pyridinium cation having a chiral moiety tethered to a urea unit. The synthesis of salt involves a reaction of 2-aminomethyl pyridine with chiral 2-isocyanate-3-methylbutyrate and then heating in the presence of alkyl halide to form salt (Scheme 17.18). In total, nine chiral pyridinium salts were synthesized with varying amino acids. Currently, the authors are using these salts for asymmetric induction in organic transformation. 

---