Amino acid-derived counterions

One stoichiometric method that avoids the use of an expensive chiral auxiliary and allows for the use of nonpyrophoric bases is based on diketopiperazine chemistry. The use of this system as a chiral auxiliary is associated with a method that was developed for the preparation of the sweetener aspartame. At the same time, we were looking at the alkylation reactions of amino acid derivatives and dipeptides. These studies showed that high degrees of asymmetric induction were not simple, were limited to expensive moieties as the chiral units, and required the use of large amounts of lithium [25,26]. The cyclic system of the diketopiperazine has been used successfully by other investigators [27,28], and we also chose to exploit the face selectivity of this unit. L-Aspartic acid was chosen as the auxiliary unit because it is readily available and cheap. All of the studies were performed with sodium as the counterion because it is a more cost-effective metal at scale. Finally, we concentrated in the use of aldehydes rather than alkyl halides to allow for a general approach and so as not to limit the reaction to reactive alkyl halides. 

To overcome reactivity problems in the imine formation with enones, the counterion was changed from a secondary to a primary amine. Additionally, having a chiral amine in the catalytic species proved to be advantageous hence, amino acid derivatives were screened, among which valine tert-butyl ester showed the best outcome. Six- and seven-membered rings turned out to be the best substrates (yields >90%), whereas cyclopentanones showed only moderate yields (68-78%). The final conditions are depicted in Scheme 32.6. ... 

Another important group of ligands for metal-catalysed reactions are based on oxazolines derived from amino acids. Evans30 has used the bis-oxazoline or box ligands in Cu(II)-catalysed Diels-Alder reactions. Ligand 133 is derived from the unnatural amino-acid /< r/-leucine and, complexed with Cu(OTf)2, catalyses Diels-Alder reactions of the same dienophile 125 with various dienes. The best counterions are triflate (OTf) and SbF6. 

Carboxylates (like amino groups) can also bind to Lewis acidic metal complexes, such as Zn-porphyrinates. In receptor 30. derived from an A -methyl porphyrin, the methyl group blocks an approach from the lower face. A carboxylate counterion must, therefore, coordinate to the top face, in the chiral environment created by the strap. When 30 (X = OAc) was dissolved in CHCI3 ani shaken with aqueous IV-acyl amino acids, many of the carbox-ylates were extracted with >80% e.e. ... 

IC-MS has also been applied for the characterization of ionic liquids (IL) and for the investigation of their long-term stability under process-like conditions. The term ionic liquid commonly refers to a class of molten salts that are by definition liquid below 100 °C. They usually consist of bulky organic cations such as alkylated imidazole, pyrrole, or pyridine derivatives, or quatemized alkyl amines and alkyl phosphines. Common counterions are halides, alkyl sulfates, fluorinated hydrocarbons, carboxylic acids, or amino acids [268]. The physical and chemical properties of ILs are customizable by different cation-anion combinations and by the length of the alkyl chain of the cation. Depending on the... 

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