Ammonium chiral

Kumar V, Olsen CE, Schaeffer SJC et al (2007) Synthesis and applications of novel bis(ammonium) chiral ionic liquids derived from isomannide. Org Lett 9 3905-3908... 

The alkyl azide 118 is reduced to a primary amine by the Pd on carbon-catalyzed reaction of ammonium formate in MeOH at room temperature. No racemization takes place with chiral azides[l 11,112]. 

Cram and his coworkers have pioneered the use of bis-binaphthyl crowns as chiral com-plexing agents for ammonium salts and amino acid salts. In these systems, the chiral binaphthyl unit provides a steric barrier within the macrocycle which allows discrimina-... 

As in the previous categories in this section, there are numerous compounds which have been prepared based on a sugar subunit. Examples may be found in Refs. 7,35,42-45, 57, 82-85, 117—121,175,176,193 and 208. Much of the work in these references has been reported by Stoddart and his coworkers, who have pioneered this field. As with the compounds prepared by Cram, the goal was to prepare a chiral receptor for ammonium ions which could be utilized in enzyme model studies. 

In supported liquid membranes, a chiral liquid is immobilized in the pores of a membrane by capillary and interfacial tension forces. The immobilized film can keep apart two miscible liquids that do not wet the porous membrane. Vaidya et al. [10] reported the effects of membrane type (structure and wettability) on the stability of solvents in the pores of the membrane. Examples of chiral separation by a supported liquid membrane are extraction of chiral ammonium cations by a supported (micro-porous polypropylene film) membrane [11] and the enantiomeric separation of propranolol (2) and bupranolol (3) by a nitrate membrane with a A/ -hexadecyl-L-hydroxy proline carrier [12]. 

The analytical capability of these matrices has been demonstrated for chiral amines [12, 13]. The procedure is illustrated in Fig. 8-4 for the separation of NapEtNH " CIO . Concentrated methanol/dichloromethane solutions of the racemic mixture were placed on a column containing the chiral macrocycle host. The enantiomers of the ammonium salts were resolved chromatographically with mixtures of methanol and dichloromethane as the mobile phase. The amounts of R and S salts in each fraction were determined by polarimetry. Because the chiral supported macrocycle interacts more strongly with S salts, the R salt passes through the column first and the S salt last, as seen in Fig. 8-4. 

The most common method of resolution uses an acid-base reaction between a racemic mixture of chiral carboxylic acids (RC02H) and an amine base (RNH2) to yield an ammonium salt. 

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. 

More recently, the same group has used a simpler and more easily prepared chiral ammonium phase-transfer catalyst 99 derived from BINOL in asymmetric Darzens reactions with a-halo amides 97 to generate glycidic tertiary amides 98 (Table 1.13). Unfortunately the selectivities were only moderate to low [48]. As mentioned in Section 1.2.3.1, tertiary amides can be converted to ketones. 

While the mechanism of the ammonium salt catalyzed alkylation is unclear, in polar solvents the enantioselectivity of the addition of dialkylzincs to aldehydes generally drops considerably, probably due to uncatalyzed product formation or complexation of the zinc reagent with the polar solvent rather than with the chiral auxiliary. 

An overall efficiency of TRISPHAT 8 and BINPHAT 15 anions as NMR chiral shift agents for chiral cations has been demonstrated over the last few years. Additions of ammonium salts of the A or A enantiomers of 8 and 15 to solutions of racemic or enantioenriched chiral cationic substrates have generally led to efficient NMR enantiodifferentiations [112-121]. Well-separated signals are usually observed on the spectra of the diastereomeric salts generated in situ. 

Sometimes, a direct ion-pairing of the chiral cations and anions 8 or 15 is necessary to maximize the NMR separation of the signals [115,116]. Cationic species as different as quaternary ammonium, phosphonium, [4]heterohelice-nium, thiiranium ions, (rj -arene)manganese, ruthenium tris(diimine) have been analyzed with success (Fig. 23). 

TRISPHAT anion 8 seems to be more particularly efficient with cationic metallo-organic and organometallic substrates. BINPHAT 15 has often-supe-rior chiral shift properties than 8 when associated with organic cations such as ammonium cation 68 (Fig. 24). In all these examples, solvent polarity influences the quality of the separation since ion association is crucial. Solvent or solvent mixtures of low polarity are preferred for these experiments. 

These salts are obtained from 1,2 (or l,3)-diamines. The cyclization step is generally the condensation of the diamines on ethyl orthoformate in the presence of ammonium tetrafluoroborate (Scheme 19). By using enantiop-ure diamines, chiral salts 34 bearing stereogenic centers on the backbone, on the nitrogen substituents, or on both were prepared [1,2,4,5,26]. Several dicyclophane imidazolinium salts have been prepared by one-pot three-step procedure [27]. 

Ever since Pasteur s work with enantiomers of sodium ammonium tartrate, the interaction of polarized light has provided a powerful, physical probe of molecular chirality [18]. What we may consider to be conventional circular dichroism (CD) arises from the different absorption of left- and right-circularly polarized light by target molecules of a specific handedness [19, 20]. However, absorption measurements made with randomly oriented samples provide a dichroism difference signal that is typically rather small. The chirally induced asymmetry or dichroism can be expressed as a Kuhn g-factor [21] defined as ... 

Sulfoxides without amino or carboxyl groups have also been resolved. Compound 3 was separated into enantiomers via salt formation between the phosphonic acid group and quinine . Separation of these diastereomeric salts was achieved by fractional crystallization from acetone. Upon passage through an acidic ion exchange column, each salt was converted to the free acid 3. Finally, the tetra-ammonium salt of each enantiomer of 3 was methylated with methyl iodide to give sulfoxide 4. The levorotatory enantiomer was shown to be completely optically pure by the use of chiral shift reagents and by comparison with a sample prepared by stereospecific synthesis (see Section II.B.l). The dextrorotatory enantiomer was found to be 70% optically pure. 

More recently, catalytic asymmetric allylations of imines and imine derivatives in aqueous media have been studied. An /V-spiro C2-symmetrical chiral quaternary ammonium salt (5,5)-I-Br (,S, .S )-()-Np-NAS-Br] has been evaluated in the allylation of glycine tert-Bu ester benzophenone Schiff base [Ph2C=NCH2COOCMe3] for synthesis of both natural and unnatural a-amino acids (Eq. 11,45).76... 

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