Mechanisms chiral phase-transfer

Efficient Asymmetric Alkylations via Chiral Phase-Transfer Catalysis Applications and Mechanism... 

Stoichiometric sulfur ylide epoxidation was first reported by A.W. Johnson [23] in 1958, and subsequently the method of Corey and Chaykovsky has found widespread use [24-26]. The first enantioselective epoxidations using stoichiometric amounts of ylide were reported in 1968 [27, 28]. In another early example, Hiyama et al. used a chiral phase-transfer catalyst (20 mol%) and stoichiometric amounts of Corey s ylide to effect asymmetric epoxidation of benzaldehyde in moderate to good enantiomeric excess (ee) of 67 to 89% [29]. Here, we will focus on epoxidations using catalytic amounts of ylide [30-32]. A general mechanism for sulfur ylide epoxidation is shown in Scheme 10.2, whereby an attack by the ylide on a carbonyl group yields a betaine intermediate which collapses to yield... 

Dolling, U. H., D. L. Hughes, A. Bhattacharya, K. M. Ryan, S. Karady, L. M. Weinstock, V. J. Grenda, and E. J. J. Grabowski, Efficient Asymmetric Alkylations via Chiral Phase-Transfer Catalysis Applications and Mechanism, Phase-Transfer Cctalysis New Chemistry, Catalysts, and AppUcatwns, C. M. Starks, ed., ACS... 

A conceptually different approach to interligand asymmetric induction uses chiral phase transfer catalysts. Scheme 3.26 illustrates two examples of such a process using an A -benzylcinchonium halide catalyst. The first is an indanone methylation [150] and the second is a glycine alkylation [151]. Hughes et al. reported a detailed kinetic study of the indanone methylation which revealed a mechanism significantly more complicated than a simple phase-transfer process the reaction is 0.55 order in catalyst and 0.7 order in methyl chloride, deprotonation of the indanone occurs at the interface, and methylation of the enolate (not deprotonation) is rate-determining [150]. Nevertheless, the rationale for the... 

FIGURE 2.45. Interphase mechanism for phase-transfer catalysis by a chiral quaternary ammonium salt. 

Alkylation Alkylation of the phenylindanone 31 with catalyst 3a by the Merck group demonstrates the reward that can accompany a careful and systematic study of a particular phase-transfer reaction (Scheme 10.3) [5d,5f,9,36], The numerous reaction variables were optimized and the kinetics and mechanism of the reaction were studied in detail. It has been proposed that the chiral induction step involves an ion-pair in which the enolate anion fits on top of the catalyst and is positioned by electrostatic and hydrogen-bonding effects as well as 71—71 stacking interactions between the aromatic rings in the catalyst and the enolate. The electrophile then preferentially approaches the ion-pair from the top (front) face, because the catalyst effectively shields the bottom-face approach. A crystal structure of the catalyst as well as calculations of the catalyst-enolate complex support this interpretation [9a,91]. Alkylations of related active methine compounds, such as 33 to 34 (Scheme 10.3), have also appeared [10,11]. 

Since asymmetric phase-transfer catalysts normally contain highly lipophilic chiral organic frameworks, and are reluctant to enter the aqueous phase, the Makosza interfacial mechanism seems plausible. 

Non-proteinogenic, chiral a.a-dialkyl-a-amino acids possessing stereochemically stable quaternary carbon centers have been significant synthetic targets, not only because they are often effective enzyme inhibitors but also because they are indispensable for the elucidation of enzymatic mechanisms. Accordingly, numerous studies have been conducted to develop truly efficient methods for their preparation [26], and in this respect phase-transfer catalysis has made unique contributions. 

While the vast majority of studies on chiral induction were mainly concerned with the induction of the chiral (twisted) nematic or cholesteric phase, more recently induction of the smectic C phase in the smectic C has come to the fore, with a special emphasis on the way chirality is transferred between molecules [ 115]. It should also be noted that comparison of the chiral induction phenomena in the two types of LC phase and in other media can provide useful information concerning mechanisms of transfer and amplification of stereochemical information [116]. 

In 2000, Zhang and Corey extended the utility of Lygo s eatalyst 8n to the asymmetrie Miehael addition of acetophenone to 4-metho3grchalcone under mild phase-transfer conditions and proposed a mechanism predicting the configuration of the chiral-adduct." Two different views of the three-dimensional arrangements of 4-methoxychalcone, the enolate of acetophenone, and catalyst 8n are shown in Scheme 16.17. 

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