Phase transfer catalyst asymmetric selection

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. 

The enantioselective synthesis of a-amino acids employing easily available and reusable chiral catalysts or reagents presents clear advantages for large-scale applications. Accordingly, recyclable fluorous chiral phase-transfer catalyst 31 has been developed by the authors group, and its high chiral efficiency and reusability demonstrated in the asymmetric alkylation of 2. After the reaction, 31 could be easily recovered by simple extraction with FC-72 (perfluorohexanes) as a fluorous solvent and used for the next run, without any loss of reactivity and selectivity (Scheme 5.17) [23]. 

Arai et al. also reported another BINOL-derived two-center phase-transfer catalyst 31 for an asymmetric Michael reaction (Scheme 6.11) [8b]. Based on the fact that BINOL and its derivatives are versatile chiral catalysts, and that bis-ammonium salts are expected to accelerate the reaction due to the two reaction sites - thus preventing an undesired reaction pathway - catalyst 31 was designed and synthesized from the di-MOM ether of (S)-BINOL in six steps. After optimization of the reaction conditions, the use of 1 mol% of catalyst 31a promoted the asymmetric Michael reaction of glycine Schiff base 8 to various Michael acceptors, with up to 75% ee. When catalyst 31b or 31c was used as a catalyst, a lower chemical yield and selectivity were obtained, indicating the importance of the interaction between tt-electrons of the aromatic rings in the catalyst and substrate. In addition, the amine moiety in catalyst 31 had an important role in enantioselectivity (34d and 34e lower yield and selectivity), while catalyst 31a gave the best results. 

The asymmetric addition of glycine enolates to acrylates was also achieved by use of the tartaric acid-derived phase-transfer catalysts 27 and 28 (Scheme 4.9). Arai, Nishida and Tsuji [13] showed that the C2-symmetric ammonium cations 27a,b afford up to 77% ee when t-butyl acrylate is used as acceptor. The cations 28 are the most effective/selective PTC identified by broad variation of the substituents present on both the acetal moiety and nitrogen atoms [14], In this study by Shibasaki et al. enantiomeric excesses up to 82% were achieved by use of the catalyst 28a (Scheme 4.9) [14], Scheme 4.9 also shows the structure of the guanidine 29 prepared by Ma and Cheng in the absence of additional base this also catalyzes the Michael addition of the glycine derivative 22 to ethyl acrylate, albeit with modest ee of 30% [15],... 

Denmark SE, Gould ND, Wolf LM (2011) A Systematic Investigation of Quaternary Ammonium Ions as Asymmetric Phase-Transfer Catalysts. Application of Quantitative Structure Activity/Selectivity Relationships. J Org Chem 76 4337... 

The spiro-type phase-transfer catalyst (188, Ar = H) possessing a C2-symmetry axis provides a single type of asymmetric environment in contrast, a newly designed spiro-type phase-transfer catalyst (188, Ar H) has two different asymmetric environments. The substituents of the binaphthyl subunits affect enantioselectiv-ity, and the 3,5-bis[3,5-bis(trifluoromethyl)phenyl]phenyl group is the best substituent of those evaluated in the anti-selective aldol reactions of glycine SchifF base 186 with aldehydes (35) (Scheme 28.21) [94]. Similarly, simpMed chiral phase-transfer catalyst 189 bearing the 3,5-bis[3,5bis(trifluoromethyl)phenyl] phenyl substituent, which is prepared in a combinatorial approach from the readily available (S)-l,l -binaphthyl-2,2 -dicarboxylic acid, effectively catalyzes syn-selective aldol reactions [95]. 

Unsaturated Sulphoxides.—Variations of known methods for the synthesis of vinyl sulphoxides are described in reports of asymmetric selectivity in the elimination of HCl from jS-halogenoethyl aryl sulphoxides using an optically active base, leading to partially resolved vinyl sulphoxides, and in reports of the condensation of carbonyl compounds with (Et0)2P(0)CHaS(0)R in the presence of a phase-transfer catalyst. Vinyl sulphoxides are formed when sulphenic acids are trapped after generation in the presence of an acetylenic ester, and a full account is available of the trapping of the sulphenic acid of... 

Takabe et al. [90] described a Cj-symmetric quaternary ammonium salt 57 and applied it to the asymmetric benzylation of N-(diphenyhnethylene) glycine tert-butyl ester. A much lower enantioselectivity was obtained by using the mono- or di-OH group-containing phase-transfer catalyst instead of (R,R,R)-57, which clearly illustrated the importance of a second coordination site to achieve reasonable selectivities. Starting from readily accessible a-amino acids, Ooi and coworkers recently designed and prepared a series of chiral 1,2,3-triazolium 58, and their potential as phase-transfer catalysts was demonstrated through application to the asymmetric alkylation of 3-substituted oxindoles [91]. 

The asymmetric epoxidation of enones with polyleucine as catalyst is called the Julia-Colonna epoxidation [27]. Although the reaction was originally performed in a triphasic solvent system [27], phase-transfer catalysis [28] or nonaqueous conditions [29] were found to increase the reaction rates considerably. The reaction can be applied to dienones, thus affording vinylepoxides with high regio- and enantio-selectivity (Scheme 9.7a) [29]. 

There are only a few reports on chiral phase transfer mediated alkylations". This approach, which seems to offer excellent opportunities for simple asymmetric procedures, has been demonstrated in the catalytic, enantioselective alkylation of racemic 6,7-dichloro-5-methoxy-2-phenyl-l-indanone (1) to form ( + )-indacrinone (4)100. /V-[4-(tnfluoromethyl)phenylmethyl]cinchoninium bromide (2) is one of the most effective catalysts for this reaction. The choice of reaction variables is very important and reaction conditions have been selected which afford very high asymmetric induction (92% cc). A transition state model 3 based on ion pairing between the indanone anion and the benzylcinchoninium cation has been proposed 10°. 

This asymmetric phase-transfer method has been applied to enantio-selective Robinson annelation as shown in Scheme 14 (41). First, alkylation of a 1-indanone derivative with the Wichtetie reagent as a methyl vinyl ketone equivalent in the presence of p-CF3BCNB gives the S-alkylation product in 92% ee and 99% yield. With 1 -(p-trifluoro-methylbenzyl)cinchonidinium bromide, a pseudo-enantiomeric diaste-reomer of p-CF3BCNB, as catalyst, the -alkylation product is obtained in 78% ee and 99% yield. These products are readily convertible to the... 

In the Park-Jew group s systematic investigation, two types of catalyst - the 1,3-phenyl- and 2,7-naphthyl-based dimeric ammonium salts - were selected as an efficient skeleton of chiral PTCs for the catalytic asymmetric phase-transfer alkylation... 

The broad substrate range, in particular with regard to the alkyl halide component, led to numerous interesting applications of this asymmetric phase-transfer-catalyzed alkylation using alkaloids as catalyst [6-18], Selected examples are described below. 

Asymmetric nucleophilic addition to C=C double bonds (see also Chapter 4) can also proceed highly stereoselectively. Several examples of enantio- and diastereo-selective Michael additions with 99% ee for the resulting products have been described by the Corey group [19]. A cinchonidine-derived phase-transfer organo-catalyst (10 mol%) was used. 

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