Epoxidation chiral PTCs

Chiral PTC has been used effectively for making intermediates for drugs. Dolling and coworkers have used 8-R, 9-5, N-(p-trifluoromethylbenzyl) cinchonium bromide to carry out an important asymmetric alkylation, giving 95% ee (Starks, 1987). Nucleophilic epoxidations of enones, Darzens reaction, Michael additions, etc. are some examples of reactions rendered asymmetric through chiral PTCs (Nelson, 1999). 

SCHEME 49. Weitz-Scheffer epoxidation of isoflavones 101 by various hydroperoxides and the chiral PTCs 103h-k... 

Asymmetric epoxidation with hydrogen peroxide as the oxidizer promoted by chiral phase-transfer catalysts (chiral PTCs, Figure 6.7) can be performed under mild... 

ASYMMETRIC EPOXIDATION OF (E)-CHALCONE CATALYZED BY THE AZACROWN ETHER-TYPE QUATERNARY AMMONIUM SALT AS CHIRAL PTC... 

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. 

Table 6.10 Asymmetric epoxidation of chalcones catalyzed by the azacrown ether-type quaternary ammonium salts as Chiral PTCs (see Figure 6.8).

Synthetic Applications of the Asymmetric Epoxidation of Enones Using Chiral PTCs... 

Adam et al. also successfully applied Wynberg s condition to the asymmetric epoxidation of isoflavones [22], Using the chiral PTC 18 and cumyl hydroperoxide (CHP) as an oxidant, the isoflavone epoxide was obtained almost quantitatively and with excellent enantio selectivity (up to 98% ee) even at a low catalyst loading (1 mol%) (Scheme 5.16). 

Besides of these main types of the chiral TAA salts, numerous other chiral TAA salts and crown ethers acting as moderately enantioselective PT catalysts were reported. Chiral PTC was mostly used for enantioselective formation of chiral carbon centers via alkylation of carbanions (enolates), Michael addition, the Darzens reaction and other reactions of carbanions. There are also numerous examples of enantioselective PTC epoxidation of electron deficient alkenes (for review, see Ref 105). 

Alkylations of phenols with epichlorohydrin under PTC conditions and microwave irradiation were described twice in 1998. Subsequently, ring-opening reactions of the epoxide group were also performed using microwaves (Eqs. 20 and 21) [31, 32]. In the first catalytic synthesis of chiral glycerol sulfide ethers was described [31] in the second biologically active amino ethers were prepared [32],... 

One of the early examples for organocatalysis is the asymmetric Weitz-Scheffer epoxidation of electron-deficient olefins, which can be effected either by organic chiral phase transfer catalysts (PTC) under biphasic conditions or by polyamino acids. This reaction has gained considerable attention and is of great synthetic use. 

The epoxidation of enones using chiral phase transfer catalysis (PTC) is an emerging technology that does not use transition metal catalysts. Lygo and To described the use of anthracenylmethyl derivatives of a cinchona alkaloid that are capable of catalyzing the epoxidation of enones with remarkable levels of asymmetric control and a one pot method for oxidation of the aUyl alcohol directly into... 

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. 

A number of attempts have been made to use optically active sulfur ylides to transfer the chirality of sulfur to carbon in the formation of epoxides and cyclopropanes. The results were somewhat disappointing. Thus, virtually no asymmetric induction was observed with the ylide (1) [475]. With the stabilized ylides (2), e.e. values in the range 7-43% were reported [476]. Better results were obtained with sulfonium ylides derived from Eliel oxathiane [477]. Optically active diaryl epoxides could be prepared under PTC in high yields and good e.e. values. 

In this system, the chiral phase transfer catalyst (PTC) is able to recognize one aldolate selectively. There is an equilibrium between syn- and anti-aldolates via retro-aldol addition, and the formation of a stable, chelated lithium salt blocks the non-catalyzed subsequent reaction from yielding the epoxide product ... 

Very recently, using structurally varied PTCs based on quinine, quinidine, dihydroquinine, and dihydroquinidine, Berkessel and coworkers conducted the asymmetric epoxidation of 2-methylnaphthoquinone (precursor of vitamin K3) with an aqueous solution of NaOCl at —10 °C in chlorobenzene [18], Among these new catalysts, the phase-transfer catalyst 13 bearing an extra chiral moiety at the quinudidine nitrogen atom provided an enantioseledivity of 79% ee with good yield (86%). However, it was found that the best results were achieved with the readily... 

Excellent conversions and selectivities were observed both with respect to the alkene and the primary oxidant [62]. In nitro-Michael reaction it was noted that the Murphy s PTC does not work as a good chiral catalyst for the Michael reaction of chalcone, but the same PTC effectively catalyses the epoxidation of chalcones with sodium hypochlorite (NaOCl) [24c]. Trials for the epoxidation of chalcone in the combination of hydroperoxides and modified guanidines 19 [27b] resulted in less effective asymmetric induction compared to the Murphy s PTC [53] (Scheme 4.21). 

Enantioselective phase-transfer catalysis (PTC) has been extensively applied for the alkylation, epoxidation, conjugate addition and related process, with the use of chiral ammonium salts being the typical transfer agent [293]. However, the related aldol... 

The introduction of a new catalyst system by Maruoka and coworkers using C2-symmetric binaphthyl-based chiral spiro ammonium salts 6 in 1999, paved the way for a new era in asymmetric phase-transfer catalysis. This PTC system was found to be highly effective for a variety of asymmetric transformations (e.g., Michael additions, a-amino acid syntheses, epoxidations. 

Besides stereoselective a-alkylation and Michael addition reactions, the epoxida-tion of a,p-unsaturated carlxMiyl acceptors using either hydrogen peroxide or hypochlorite as the oxygen source has emerged as a powerful methodology imder chiral phase-transfer cmiditimis. As an example for the potential of this methodology, the PTC-mediated stereoselective synthesis of loxistatin (88) was reported by Lygo et al. in 2006 [55], Herein, the diastereoselective epoxidation of enmie 89 has been employed as a key step in this sequence (Scheme 17). 

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