Epoxides asymmetric phase-transfer

Epoxidation is another important area which has been actively investigated on asymmetric phase transfer catalysis. Especially, the epoxidation of various (i.)-a,p-unsaturated ketones 68 has been investigated in detail utilizing the ammonium salts derived from cinchonine and cinchonidine, and highly enantioselective and diastereoselective epoxidation has now been attained. When 30 % aqueons H202 was utilized in the epoxidation of various a, 3-unsaturated ketones 68, use of the 4-iodobenzyl cin-choninium bromide 7 (R=I, X=Br) together with LiOH in Bu20 afforded the a,p-epoxy ketones 88 up to 92% ee,1641 as shown in Table 5. The O-substituted... 

Excellent enantioselectivities have not been attained in the asymmetric phase transfer catalyzed epoxidation of (Z)-enones in contrast to that of (E)-enones. However, a few promising results168,691 have been reported on the epoxidation of 2-substituted... 

B. Lygo, P. G. Wainwright, Asymmetric Phase-Transfer Mediated Epoxidation of a,p-Unsaturated Ketones using Catalysts Derived from Cinchona Alkaloids , Tetrahedron Lett. 1998,39,1599-1602. 

Figure 16. Transition states for asymmetric phase-transfer-catalyzed epoxidation of cyclqhexenones (77).

Lygo, B. and To, D.C.M., Asymmetric Epoxidation via Phase-transfer Catalysis Direct Conversion of Allylic Alcohols into a, -Epoxyketones. Chem. Commun. 2002, 2360-2361. 

Lygo and Wainwright recently reported a detailed study of the asymmetric phase-transfer mediated epoxidation of a variety of acyclic a,P-unsaturated ketones of the chalcone type. The third-generation cinchona-derived quats (8c and 7c), related to those discussed earlier in the alkylation section and Scheme 10.4, gave the best inductions (89% ee, 88 to 89, Scheme 10.13 and 86% ee for the pseudoenantiomeric catalyst 7c to give, as product, the enantiomer of 89). 

The use of chiral crown ethers as asymmetric phase-transfer catalysts is largely due to the studies of Bako and Toke [6], as discussed below. Interestingly, chiral crown ethers have not been widely used for the synthesis of amino acid derivatives, but have been shown to be effective catalysts for asymmetric Michael additions of nitro-alkane enolates, for Darzens condensations, and for asymmetric epoxidations of a,P-unsaturated carbonyl compounds. 

Very recently, Belokon and North have extended the use of square planar metal-salen complexes as asymmetric phase-transfer catalysts to the Darzens condensation. These authors first studied the uncatalyzed addition of amides 43a-c to aldehydes under heterogeneous (solid base in organic solvent) reaction conditions, as shown in Scheme 8.19 [47]. It was found that the relative configuration of the epoxyamides 44a,b could be controlled by choice of the appropriate leaving group within substrate 43a-c, base and solvent. Thus, the use of chloro-amide 43a with sodium hydroxide in DCM gave predominantly or exclusively the trans-epoxide 44a this was consistent with the reaction proceeding via a thermodynamically controlled aldol condensation... 

Michael-aldol reaction as an alternative to the Morita-Baylis-Hillman reaction 14 recent results in conjugate addition of nitroalkanes to electron-poor alkenes 15 asymmetric cyclopropanation of chiral (l-phosphoryl)vinyl sulfoxides 16 synthetic methodology using tertiary phosphines as nucleophilic catalysts in combination with allenoates or 2-alkynoates 17 recent advances in the transition metal-catalysed asymmetric hydrosilylation of ketones, imines, and electrophilic C=C bonds 18 Michael additions catalysed by transition metals and lanthanide species 19 recent progress in asymmetric organocatalysis, including the aldol reaction, Mannich reaction, Michael addition, cycloadditions, allylation, epoxidation, and phase-transfer catalysis 20 and nucleophilic phosphine organocatalysis.21... 

Asymmetric Phase Transfer Catalysis Asymmetric Epoxidation Reactions... 

The asymmetric epoxidation of electron-deficient olefins, particularly a,/3-enones, including the use of chiral metal hydroperoxides, asymmetric phase-transfer methods, polyamino acid catalysts, and the chiral dioxiranes, has been reviewed <2000CC1215>. 

The asymmetric phase-transfer epoxidation of ( )-a, 3-unsaturated sulfones has recently been achieved by Dorow and coworker using N-anthracenylmethyl cinchona alkaloid derivatives as catalysts and KOC1 as an oxidant at low temperature [23]. The screening of several etheral functional groups at the C9( O) position of the catalyst moiety indicated that the steric size and the electronic factor of the ether substituent has a significant effect on both the reaction conversion and the enantioselectivity. 

Optically active epoxides. Wynberg et al have achieved asymmetric induction in epoxidations under phase-transfer conditions using the quaternary ammonium salt (1) derived from quinine. The oxidation was carried out with 307o aqueous H2O2 (t-butyl hydroperoxide was used in one instance) with... 

Some other very important events in the historic development of asymmetric organocatalysis appeared between 1980 and the late 1990s, such as the development of the enantioselective alkylation of enolates using cinchona-alkaloid-based quaternary ammonium salts under phase-transfer conditions or the use of chiral Bronsted acids by Inoue or Jacobsen for the asymmetric hydro-cyanation of aldehydes and imines respectively. These initial reports acted as the launching point for a very rich chemistry that was extensively developed in the following years, such as the enantioselective catalysis by H-bonding activation or the asymmetric phase-transfer catalysis. The same would apply to the development of enantioselective versions of the Morita-Baylis-Hillman reaction,to the use of polyamino acids for the epoxidation of enones, also known as the Julia epoxidation or to the chemistry by Denmark in the phosphor-amide-catalyzed aldol reaction. ... 

Asymmetric phase-transfer catalyzed cascades initiated by the conjugate addition of heteronucleophiles has been employed for the enantioselective preparation of epoxides and aziridines using a suitable oxygen- or nitrogen-based nucleophile incorporating an appropriate leaving group ready to... 

Scheme 16.37 Asymmetric phase-transfer catalytic epoxidation of chalcones.

ShibasaM M, Ohshima T, Gnanadesikan V, Shibuguchi T, Fukuta Y, Nemoto T (2003) Enantioselective Syntheses of Aeruginosin 298-A and its Analogues Using a Catalytie Asymmetric Phase-Transfer Reaction and Epoxidation. J Am Chem Soc 125 11206... 

Enantioselective oxidation is one of the most important and yet useful transformations in organic synthesis, and the asymmetric phase-transfer catalysis has made notable contributions to this field. The stereoselective epoxidation of electron-deficient olefins with peroxides is a representative example, and Taylor demonstrated the synthetic utility of this system by accomplishing the total syntheses of three natural products of manumycin family, (-l-)-MT 35214 131, (-l-)-manumycin A 132, " and (—)-alisamycin 133 (Scheme 4.31). The syntheses were undertaken by the... 

A and its analogues using a catalytic asymmetric phase-transfer reaction and epoxidation. J. Am. Chem. Soc. 2003 125(37) 11206-11207. 

Lygo and co-workers used an asymmetric phase-transfer-catalyzed epoxidation in the stereoselective... 

Taylor and co-workers employed an asymmetric phase-transfer-catalyzed epoxidation as the key step in the synthesis of (+)-manumycin and revised the structural assignment for the natural antibiotic (—)-manumycin (Scheme 35.31). Using A-benzylcinchonidinium chloride 111 as the phase-transfer catalyst, asymmetric epoxidation of cw-enone 112 provided epoxide 113 in 32% yield (82% based on recovered 112) and 89% ee (>99% ee after recrystallizations). Epoxide 113 was finally transformed into... 

SCHEME 3531. An asymmetric phase-transfer atalyzed epoxidation as the key step in the s)mthesis of (+)-manumycin. 

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. 

Ohshima, T., Gnanadesikan, V., Shibuguchi, T, Fukuta, Y., Nemoto, T., and Shibasaki, M. (2003) Enantioselective syntheses of aeruginosin 298-A and its analogues using a catalytic asymmetric phase-transfer reaction and epoxidation./. Am. Chem. Soc., 125,11206-11207. 

Murphy and coworkers prepared similar guanidinium salts 54 from commercially available ethyl (J )-3-hydroxybutyrate and (S)-(—)-mahc acid [86]. The application of the catalysts 54 in the phase-transfer-catalyzed epoxidation of the chalcones delivered high enantioselectivities. Recently, Tan and coworkers developed a series of chiral pentanidium salts 55, which could be successfully applied to the asymmetric phase-transfer-catalyzed conjugate addition [87] as well as a-hydroxylation reactions [88]. 

In addition, NaOMe, and NaNH2, have also been employed. Applieation of phase-transfer conditions with tetra-n-butylammonium iodide showed marked improvement for the epoxide formation. Furthermore, many complex substituted sulfur ylides have been synthesized and utilized. For instance, stabilized ylide 20 was prepared and treated with a-D-a/lo-pyranoside 19 to furnish a-D-cyclopropanyl-pyranoside 21. Other examples of substituted sulfur ylides include 22-25, among which aminosulfoxonium ylide 25, sometimes known as Johnson s ylide, belongs to another category. The aminosulfoxonium ylides possess the configurational stability and thermal stability not enjoyed by the sulfonium and sulfoxonium ylides, thereby are more suitable for asymmetric synthesis. 

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]. 

---