Chiral quaternary ammonium salts

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... 

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). 

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... 

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. 

M. Horikawa, J. Bush-Petersen, E. J. Corey, Enantioselective Synthesis of P-Hydroxy-a-amino Acid Esters by Adol Coupling Using a Chiral Quaternary Ammonium Salt as Catalyst , Tetrahedron Lett. 1999, 40, 3843-3846. 

E. J. Corey, E-Y. Zhang, re and si-Face-Selective Nitroal-dol Reactions Catalyzed by a Rigid Chiral Quaternary Ammonium Salt A Highly Stereoselective Synthesis of the HIV Protease Inhibitor Amprenavir (Vertex 478) , Angew. Chern. Int. Ed 1999, 38,1931-1934. 

K. Soai, M. Watanabe, Chiral Quaternary Ammonium Salts as Solid State Catalysts for the Enantioselective Addition of Diethylzinc to Aldehydes , J. Chem Soc, Chern. Commun 1990, 43-44. 

S. Chang, J. M. Galvin, E. N. Jacobsen, Effect of Chiral Quaternary Ammonium Salts on (salen)Mn-Catalyzed Epoxidation of ds-Olefms. A Highly Enantioselective,... 

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). 

General procedures for the preparation of typical chiral quaternary ammonium salts... 

Miscellaneous PTC Reactions The field of PTC is constantly expanding toward the discovery of new enantioselective transformations. Indeed, more recent applications have demonstrated the capacity of chiral quaternary ammonium salts to catalyze a number of transformations, including the Neber rearrangement (Scheme 11.19a), ° the trifluoromethylation of carbonyl compounds (Scheme 11.19b), ° the Mannich reaction (Scheme 11.19c), and the nucleophilic aromatic substitution (SnAt)... 

Hori et have recently reported aza crown ether chiral quaternary ammonium salts for the epoxidation of ( )-chalcone with alkaline hydrogen peroxide as the terminal oxidant. The oxidation proceeded in high yield and good enantio-selectivity the success of the reaction depended on the length of the carbon chain on the nitrogen atom. These PTC catalysts are shown in Figure 1.50. 

Hori, K., Tamura, M., Tani, K., Nishiwaki, N., Ariga, M. and Tohda, Y. Asymmetric Epoxidation Catalyzed by Novel Azacrown Ether-type Chiral Quaternary Ammonium Salts under Phase-transfer Catalytic Conditions. Tetrahedron Lett. 2006, 47, 3115-3118. 

ASYMMETRIC EPOXIDATION CATALYZED BY NOVEL AZACROWN ETHER-TYPE CHIRAL QUATERNARY AMMONIUM SALTS UNDER PHASE-TRANSFER CATALYTIC CONDITIONS... 

The azacrown ether-type chiral quaternary ammonium salts as chiral PTCs are easily prepared from BINOL in four steps. Remarkably, Table 6.10 shows that the good efficiency of asymmetric epoxidation of various chalcones can be achieved by adjustment of the length of the carbon chains on the nitrogen atom in the quaternary ammonium salts. 

Chiral solvomercuration was accomplished by carrying out the reaction of alkenes with Hg(OAc)2 in the presence of chiral quaternary ammonium salts synthesized from natural ephedrine.642 Chiral secondary alcohols may be isolated with ee values up to 96%. Chiral nitrogen-containing diselenides are transformed by perox-odisulfate to selenium electrophiles, which may add to alkenes to form oxyseleny-lation products. These are, however, not isolated but oxidized to induce oxidative p-hydride elimination to afford chiral allyl methyl ethers with ee values up to 75%.643... 

Some organic reactions can be accomplished by using two-layer systems in which phase-transfer catalysts play an important role (34). The phase-transfer reaction proceeds via ion pairs, and asymmetric induction is expected to emerge when chiral quaternary ammonium salts are used. The ion-pair interaction, however, is usually not strong enough to control the absolute stereochemistry of the reaction (35). Numerous trials have resulted in low or only moderate stereoselectivity, probably because of the loose orientation of the ion-paired intermediates or transition states. These reactions include, but are not limited to, carbene addition to alkenes, reaction of sulfur ylides and aldehydes, nucleophilic substitution of secondary alkyl halides, Darzens reaction, chlorination... 

See Phase-transfer catalysts (this volume) for another example of a chiral quaternary ammonium salt. 

Crown ethers have given impressive enantioselectivites in Michael additions (Chart 10.2). Purely synthetic chiral crowns are of limited use on large scale based on cost although, in general, the crowns are less susceptible to catalyst degradation and, therefore, have higher catalyst turnover numbers than the chiral quaternary ammonium salts. Of interest are crowns with symmetry, aza-crowns, and those with sugars or other chiral-pool units as sources of chirality (Charts 2 and 4). 

Cyclopropanation, Horner-Wadsworth Emmons Reaction, and Darzens Condensation Although induction in the cyclopropanation of alkenes was reported early, this work was disputed [49]. Other reports of cyclopropanations have yielded, at best, low asymmetric inductions [llh,50]. The first example of a catalytic asymmetric Horner-Wadsworth Emmons reaction, which is promoted by a chiral quaternary ammonium salt, was reported recently by the Shioiri group (Scheme 10.10) [51]. The reaction of the prochiral ketone 74 gives optically active a,P-unsaturated ester 76 with 57% ee. 

Jacobsen and co-workers have found that catalytic amounts of chiral quaternary ammonium salts, such as 6i, promote a dramatic reversal in the diastereoselectivity of (salen)Mn-catalyzed epoxidation of cis-alkenes, resulting in a highly enantioselective catalytic route to trans-epoxides (Scheme 10.14) [72]. 

In 1989, O Donnell and coworkers successfully utilized cinchona alkaloid-derived chiral quaternary ammonium salts for the asymmetric synthesis of a-amino acids using tert-butyl glycinate benzophenone Schiff base 1 as a key substrate [5]. The asymmetric alkylation of 1 proceeded smoothly under mild phase-transfer... 

Recently, Castle and coworkers introduced C3-alkyny]-substituted chiral quaternary ammonium salt of type 41, and evaluated its ability as a chiral phase-transfer catalyst in the aldol reaction between 1 and hydrocinnamaldehyde using BTTP as a base, in which a high level of enantioselectivity (91% ee) was observed for syn-22 (Scheme 2.19) [41],... 

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... 

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]. 

Maruoka and coworkers recently developed an efficient, highly diastereo- and enantioselective direct aldol reaction of glycine Schiff base 2 with a wide range of aliphatic aldehydes under mild phase-transfer conditions employing N-spiro chiral quaternary ammonium salt li as a key catalyst, as shown in Table 5.12 [41a]. 

The development of various types of chiral phase-transfer catalyst relies largely on the molecular design of both natural product-derived and purely synthetic chiral quaternary ammonium salts. This approach often delivers not only higher reactivity... 

The chiral quaternary ammonium salt 47a with a single tartrate moiety and free hydroxyl groups gave disappointing results for the Michael addition of Schiff s base 20 with tert-butyl acrylate in the presence of CsOH base. However, the benzyl-protected catalyst 47b promoted Michael addition, and the adduct (S)-49 was obtained in 57% yield, although the enantioselectivity remained low (Table 7.6, entry 2). The use of catalyst 48a,b with two tartrate moieties afforded the best results at —60 ° C, and Michael adduct (S)-49 was obtained in good enantioselectivity up to 77% ee (entries 4 and 5). 

A biphenyl and ct-methylnaphthylamine-derived chiral quaternary ammonium salt 23d, which was shown by Lygo to be effective for the asymmetric alkylation of Schiffs base 20, was also effective in the Michael reaction (Scheme 7.12) [43]. Notably, the enantioselectivity was highly dependent on the reaction conditions and substrates used. The Michael reaction of imine esters such as benzhydryl and benzyl esters with a,p-unsaturated ketones under solid-liquid phase-transfer catalysis conditions afforded the Michael adduct in up to 94% ee and 91% ee, respectively, while the tert-butyl ester showed moderate enantioselectivity (Scheme 7.12). Interestingly, in contrast to earlier reports, acrylate [42] and acrylamides failed to undergo the Michael reaction under these optimized conditions. 

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