Ammonium salts chiral

In addition, Snyder demonstrated that the use of a lipophilic quaternary proUne-derived ammonium salt chiral selector to transfer the nucleophile (a hydroxide ion) from the aqueous layer to the organic layer containing an electron-deficient arene allows the spectroscopic characterization... 

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-... 

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. 

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. 

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... 

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>. 

The Z)3-symmetric TRISPHAT anion 88, tris(tetrachlorobenzenediolato)phosphate, is chiral and configurationally stable. It can be resolved by association with chiral ammonium salts such as cinchonidine <1997AGE608, 2004JOC8521>. TRISPHAT 88 displays high selectivity for cinchonidine and does not associate with the related diasteromer cinchonine <1998TL4825>. The selective ion pairing behavior of TRISPHAT has been exploited in... 

A chiral [4]pseudocatenane 16 was synthesized from chiral triptycene-based /m( crown ether) and three equivalents of hw[p-(but-3-enyloxy)benzyl]ammonium salt in CH2CI2 in the presence of Grubbs II catalyst, followed by reduction <06CEJ5603>. Several novel calix[4]arenocrowns were prepared by a simple one-pot reaction of calix[4]monohydroquinone diacetate with bw-tosylates, e.g. l,4-bw[2-(2-(2-(2-tosyloxy-ethoxy)ethoxy)ethoxy)ethoxy)benzene, in dry MeCN in the presence of NaOH the self-assembly into calix[4]areno[2]catenanes with a dicationic salt and />-bfr(bromomethyl)-benzene was also demonstrated <06TL6012>. 

A system exhibiting chiral recognition. The chiral macrotricyclic tet-raamide (250) (Lehn, Simon Moradpour, 1978) has been used for the complexation, extraction and transport of primary ammonium salts. The tetraamide was used rather than the corresponding tetraamine because of the lower basicity of the nitrogens in the former ligand. This avoids the possibility of proton transfer occurring from the primary ammonium substrates R-NH3+ used as guests. In a typical experiment, a solution of a primary ammonium salt, such as naphthylethyl ammonium or phenylalanine methylester hydrochloride in hydrochloric acid was... 

A young Louis Pasteur observed that many salts of tartaric acid formed chiral crystals (which he knew was related to their ability to rotate the plane of polarization of plane-polarized light). He succeeded in solving the mystery of racemic acid when he found that the sodium ammonium salt of racemic acid could be crystallized to produce a crystal conglomerate. After physical separation of the macroscopic enantiomers with a dissecting needle, Pasteur... 

Amines with three different substituents are potentially chiral because of the pseudotetrahedral arrangement of the three groups and the lone-pair electrons. Under normal conditions, however, these enantiomers are not separable because of the rapid inversion at the nitrogen center. As soon as the lone-pair electrons are fixed by the formation of quaternary ammonium salts, tertiary amide N-oxide, or any other fixed bonding, the inversion is prohibited, and consequently the enantiomers of chiral nitrogen compounds can be separated. 

Chiral quaternary ammonium salts in solid state have also been used as catalysts for the enantioselective addition of diethylzinc to aldehydes (Scheme 2-45).112 In most cases, homogeneous chiral catalysts afford higher enantio-selectivities than heterogeneous ones. Scheme 2-45 presents an unusual asymmetric reaction in which chiral catalysts in the solid state afford much higher enantioselectivities than its homogeneous counterpart.112... 

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... 

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 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 quaternary ammonium salt 48 derived from (+)-ephedrine was utilized for the enantioselective addition of diethyl zinc to aldehydes.1421 The chiral ammonium fluorides 7 (R=4-CF3 or 2,4-(CF3)2, X=F) were also useful for the enantioselective trifluoro-methylation of aldehydes and ketones with moderate enantioselectivity,1431 shown in Scheme 17... 

Some chiral quaternary ammonium salts are also effective in Michael addition reactions. The Merck catalysts 7 (R=4-CF3, X=Br) and 9 (R=4-CF3, X=Br, 10,11-dihydro) were used tor the Michael additions of 59,61, and 64 to vinyl ketones to give the adducts 60,62, and 65 (isolated as 66), respectively,148,491 with excellent enantioselectivity, as shown in Scheme 19. The Michael addition of the O Donnell imine 23 to the a,(3-unsaturated carbonyl compounds also efficiently proceeded by use of the N-anthracenyl-methyl catalyst 12 (R=allyl, X=Br), giving the Michael adducts 67 (Scheme 20).1251... 

The asymmetric Darzens condensation, which involves both carbon-carbon and carbon-oxygen bond constructions, was realized by use of the chiral azacrown ether 75als2,s ,ss and the quaternary ammonium salts derived from cinchona alka-loids159"621 under phase transfer catalyzed conditions. The a,p-epoxy ketone 80 (R=Ph) was obtained with reasonable enantioselectivity by the reaction of... 

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