Quaternary catalytic efficiency

Smith and co-workers have employed NHC 81 to catalyse the 0- to C-carboxyl transfer of a range of oxazolyl carbonates 80, forming 82 with the generation of a C-C bond at a quaternary centre with good catalytic efficiency [27], This transformation presumably proceeds via the generation of an intermediate carboxyazolium species, and has been utihsed as a component of domino multi-component reactions [28], as well as the rearrangement of indolyl and benzofuranyl carbonates (Scheme 12.15) [29]. 

The direct quaternization of chloromethylated polystyrenes by tertiary amines or phosphines represents the easiest way to obtain polymer-supported quaternary onium salt (12,13). A lipophilic character of quaternary cation and a topology allowing sufficient cation-anion separation also play an important role (35,36). A linear spacer chain (of about 10 carbon atoms) between the catalytic site and the polymer backbone substantially increases the reaction rates. The loading of quaternary onium groups also affects catalytic efficiency, the influence being different for directly bonded and spaced groups, e.g. 10 and 11, respectively (37). 

Immobilization of phase-transfer catalysts on polymeric matrices avoids the problem of separating and recycling the catalysts. In this case the chemical stability of the immobilized catalyst becomes very important quaternary salts often decompose under drastic reaction conditions whereas polydentate ligands are always stable. However, the difficult synthesis of cryptands, despite their high catalytic efficiency, can hardly justify their use. Synthesis of crown-ethers is much easier, but catalytic efficiences are often too low. 

In 2000, Benaglia and coworkers reported preparation of MeO-PEG supported quaternary ammonium salt (10) and examined the catalytic efficiency in a series of phase-transfer reactions (Fig. 5.3) [69]. The reactions occurred at lower temperatures and with shorter reaction times than with comparable insoluble 2% cross-linked polystyrene-supported quaternary ammonium salts, although yields varied with respect to classical solution phase quaternary ammonium salt catalyzed reactions. It was observed that yields dropped with a shorter linker, and that PEG alone was not responsible for the extent of phase-transfer catalysis. While the catalyst was recovered in good yield by precipitation, it contained an undetermined amount of sodium hydroxide, although the presence of this byproduct was found to have no effect on the recyclability of the catalyst... 

Being inspired by Maruoka s results with the C2-symmetric binaphthyl-derived quaternary ammonium salt [21], Lygo and colleagues designed a quaternary ammonium salt 23, comprising conformationally flexible biphenyl units and commercially available chiral secondary amines [22], A library of 40 quaternary ammonium salt was synthesized and evaluated for their catalytic efficiency in the asymmetric alkylation of... 

At very negative potentials neither the tetraalkylammonium ions nor the metallic electrode are inert they combine to form reduced TAA-metals [7]. Tetraalkylammonium (TAA) metals are composed of quaternary ammonium ions, electrons, and a post-transistion metal such as Hg, Pb, Sn, Sb, Bi [5-18] or Pt [19] most of them have the composition R4N" MeJ [13] or R4N" Mc4 [20] and have been described as Zintl ion salts or Zintl phases [21,22]. They have been shown to be useful intermediates in the electrochemical reduction of certain substrates that are reducible with difficulty. On reduction of the quaternary ammonium salt, the initial layer of the metal compound is controlled by a two-dimensional nucleation, whereas the bulk phase is initiated by a three-dimensional nucleation and a growth controlled by the diffusion of R4N from the solution. In some cases (A-methylquinuclidinium (MQ" ) mercury) the catalytic efficiency of the initial layer is greater than that of the bulk phase [18], whereas in other cases (A, A-dimethylpyrrolidinium (DMP" ) lead) the opposite is found [16]. 

Evaluation of phase-transfer catalysts. Herriott and Picker have examined the catalytic effects of 21 quaternary ammonium and phosphonium salts on the Sn2 reaction of sodium thiophenoxide with 1-bromooctane in a two-phase system of aqueous sodium hydroxide and an organic solvent. They report the following conclusions The catalytic efficiency increases with the length of the... 

Subsequently, it was found that the catalytic efficiency of a quaternary salt is directly related to its solubility in the organic phase, other conditions being the same. This and other observations support the mechanism reported in Fig. 2, in which anion transfer does not necessarily require the partitioning of the quaternary cation, the charge parity in both phases being ensured by the quaternary and the metal cation, respectively. ... 

These results are consistent with those obtained under similar conditions with quaternary salts. Second-order rate constants are also very similar in both cases (Table 9). However, the catalytic efficiencies of 3 and quaternary salts differ greatly. 

Very recently, the Siva group successfully reported a chiral multisite phase-transfer catalytic Michael addition by the use of 2,4,6-(triscincho-niummethyl)phenyl-l,3,5-triazines as new polymeric chiral quaternary ammonium PTC catalysts. Catalyst 12c showed a higher catalytic efficiency than the corresponding monomeric catalyst 8q in terms of chemical yield and enantioselectivity due to the trimeric reaction sites of 12c, which can promote efficient ion-pair interactions between the a-carbon of the diethyl-malonate and trimeric catalysts due to steric factors (Scheme 16.22). ... 

Based on the catalyst design limitation arising from their synthesis, other chiral quaternary ammonium salts were developed, such as Ca-symmetrical PTC catalysts XXVIII [53], spermidine- and spermine-based catalysts XXIX [54], bis-biphenyl quaternary ammonium salts XXX [55], and other chiral quaternary ammonium salts of types XXXI and XXXII [56]. V-spiro chiral ammonium salt XXXI and XXXII (the later, readily available from gallic acid) possessing flexible alkyl chains showed high catalytic efficiency in alkylations of glycine-imine esters even in the presence of 0.01-0.05 mol% of XXXI or XXXII (Scheme 8.6) [57]. 

The addition of alcohol, as cosurfactant, to the [Cgmim][TfjN]/AOT/water system leads to stable w/IL microemulsions. DLS and protein solubilization experiments confirm the existence of an aqueous nanoenvironment in the IL phase of [C mirnTf N]/ AOT/l-hexanol/water microemulsions [67]. The kinetics of the enzymatic reactions were performed in this quaternary system. Specifically, lipase-catalyzed hydrolysis of p-nitrophenyl butyrate (p-NPB) was used as a model reaction [68]. In a similar way, the hpase-catalyzed hydrolysis of p-NPB was investigated to evaluate the catalytic efficiency in water/AOT/Triton X-100/[C mim][PFJ [69]. A large single-phase microemulsion region can be obtained from the combination of two surfactants in IL. 

Tertiary amines are also known to effect the phase transfer addition of cyanide ion to primary, allylic, and benzylic halides [9]. The reported effect of amine structure on catalytic efficiency closely parallels that reported by Hennis for ester formation in a two-phase system (see Sect. 1.7). Both the nitrogen of the amine and the carbon bearing halide of the alkyl bromide must be sterically accessible for the reaction to succeed. Thus, -hexylamine is effective in concert with -butyl bromide but the combinations of either 5-butyl bromide and -hexylamine or -butyl bromide and cyclohexylamine are not. Tertiary amines are generally more effective than secondary or primary amines. In addition, the yields of primary nitriles decrease dramatically with the size of the primary alkyl bromide from quantitative with n-butyl to only 6% with -decyl bromide when -hexylamine is used as phase transfer catalyst. On the other hand, tributylamine was equally useful as a catalyst for the quantitative conversion of either 1-bromohexane or 1-bromodecane to the corresponding nitriles [9]. In general, these observations accord with those of Hennis and coworkers indicating that this reaction is an example of in situ formation of and catalysis by quaternary ammonium salts [10]. 

The most satisfactory results so far in this area are to be found in a report of the reaction of benzaldehyde with trimethylsulphonium iodide and aqueous base according to equation (10), where, under optimum conditions and catalysed by (23 R = C2H5), up to 97% enantiomer excess in the oxirane product can be achieved. Possible rationalizations have been discussed for these processes, and the role of the )S-hydroxyethyl substituent at the quaternary centre seems to be significant in both catalytic efficiency and enantioselectivity. Further advances in this field can be expected. 

Nucleophilic Substitutions.—Many of the nucleophilic substitutions covered by equation (1) can be catalysed as effectively in liquid-liquid two-phase systems by crown and cryptand compounds as by quaternary ions. Alkyl substitution on the basic crown skeleton of (28), as in (31), was found to increase the efficiency of catalysis for the conversion of alkyl mesylates to halides, presumably by ensuring partitioning of the crown-salt complex between the phases. A similar observation has been made using alkyl-substituted crown (32) and aza-crown compounds (33) as catalysts in two-phase reactions, for example between iodide, cyanide or thiocyanate aniohs and an alkyl bromide. Alkyl substitution in the macrobicyclic cryptands (34) has the same effect on Sn processes, and in all the above cases systems can be devised with catalytic efficiency comparable to or greater than that achieved by quaternary ion PTC. 

An important observation with respect to these catalytic systems is the fact that the presence of quaternary ammonium salts (R N X ) notably enhances their catalytic efficiencies. As mentioned earlier (see Section 3.2.5), in these ligandless systems, complexes such as [(Ar) (Solvent)PdXJ and [Ar(alkene)PdX2] are detected by extended X-ray absorption fine structure (EXAFS). 

Silica gel-based catalytic systems have been described as efficient promoters for a number of organic reactions.28 Illustrative examples include the oxidative cleavage of double bonds catalyzed by silica-supported KM11O4,29 reaction of epoxides with lithium halides to give /i-halohydrins performed on silica gel,30 selective deprotection of terf-butyldimethylsilyl ethers catalyzed by silica gel-supported phosphomolybdic acid (PMA),31 and synthesis of cyclic carbonates from epoxides and carbon dioxide over silica-supported quaternary ammonium salts.32... 

Pd-catalyzed Heck reactions are among the most effective methods for the formation of quaternary carbon centers. Considering the significance and the strategic difficulties associated with the synthesis of quaternaiy carbons, particularly in the optically enriched or pure form, it is not a surprise that the development of catalytic asymmetric Heck reactions has held center stage for the past few years. One of the leading labs in this area is that of Shibasaki, who in 1993 reported a concise total synthesis of eptazodne 23 (Scheme 4).141 Thus, treatment of silyl ether 18 with 10 mol% Pd(OAc>2 and 25 mol% (S)-19 leads to the formation of 20 in 90 % yield and 90% ee As illustrated in Scheme 4, once the quaternary carbon center is synthesized efficiently and selectively, the target molecule is accessed in a few steps. 

T. Takemoto, M. Sodeoka, H. Sasai, M. Shibasaki Catalytic Asymmetric Synthesis of Benzylic Quaternary Carbon Centers. An Efficient Synthesis of (-)-Eptazocine , J. Am. Chem. Soc 1993,115, 8477-8478. 

Increasing the hydrophobicity of quaternary ammonium salts increases the apparent extraction constants for the ion pair and therefore leads to a higher catalytic activity (Brandstrom, 1977). The same phenomenon has been observed by Cinquini and Tundo (1976) for crown ether catalysis (Table 35). The catalytic activity of 18-crown-6 [3] and alkyl-substituted derivatives [117]—[ 119] in the reaction of n-CgH17Br with aqueous KI follows the order [117], [118] > [119] s> [3]. The alkyl-substituted [2.2]-cryptand derivatives are also much more efficient than the parent compound [86]. Increasing the hydrophobicity of [2.2.2]-cryptand (Cinquini et al., 1975) and even of polypode ligands (Fornasier et al., 1976) leads to higher catalytic activity. The tetradecyl-substituted compounds show the reactivity sequence [2.2.2]-cryptand at 18-crown-6 > [2.2]-cryptand on the reactivity scale that can be distilled from Table 35. 

The Hoffman rearrangement of amides by quaternary ammonium hypochlorites is not particularly efficient under phase-transfer catalytic conditions and only low yields of nitrile, aldehydes, or ketones, which result from oxidation of the amines, are... 

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