Cinchona alkaloid catalysts epoxidation

One of the most significant developmental advances in the Jacobsen-Katsuki epoxidation reaction was the discovery that certain additives can have a profound and often beneficial effect on the reaction. Katsuki first discovered that iV-oxides were particularly beneficial additives. Since then it has become clear that the addition of iV-oxides such as 4-phenylpyridine-iV-oxide (4-PPNO) often increases catalyst turnovers, improves enantioselectivity, diastereoselectivity, and epoxides yields. Other additives that have been found to be especially beneficial under certain conditions are imidazole and cinchona alkaloid derived salts vide infra). 

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. 

Epoxidations and Darzens Condensations The asymmetric catalytic epoxida-tion of a,p-unsaturated ketones using cinchona alkaloid-derived catalysts was introduced in the 19708. However, high levels of enantioselectivity were achieved only 20 years later, when Lygo, Arai, 2-t94 others P ... 

Darzens condensation using crown ethers and cinchona alkaloids-derived catalysts, respectively, obtaining epoxides with moderate enantioselectivity. 

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... 

Asymmetric epoxidation catalyzed by chiral phase-transfer catalysts is another reaction which has been extensively studied following an initial report by Wynberg [2,44]. Shioiri et al. further improved the enantioselective epoxidation of naphthoquinones under cinchona alkaloid-derived chiral phase-transfer catalysis [45],... 

Dehmlow and coworkers [17] compared the efficiency of monodeazadnchona alkaloid derivatives 14a-c in the enantioselective epoxidation of naphthoquinone 50 with that of cinchona alkaloid-derived chiral phase-transfer catalysts 15a-c (Table 7.7) (for comparison of the alkylation reaction, see Table 7.1). Interestingly, the non-natural cinchona alkaloid analogues 14a-c afforded better results than natural cinchona alkaloids 15a-c. The deazacinchonine derivatives 14a,b produced epoxidation product 51 in higher enantioselectivity than the related cinchona alkaloids 15a,b. Of note, catalyst 14c, which possessed a bulky 9-anthracenylmethyl substituent on the quaternary nitrogen, afforded the highest enantioselectivity (84% ee). 

Another important asymmetric epoxidation of a conjugated systems is the reaction of alkenes with polyleucine, DBU and urea H2O2, giving an epoxy-carbonyl compound with good enantioselectivity. The hydroperoxide anion epoxidation of conjugated carbonyl compounds with a polyamino acid, such as poly-L-alanine or poly-L-leucine is known as the Julia—Colonna epoxidation Epoxidation of conjugated ketones to give nonracemic epoxy-ketones was done with aq. NaOCl and a Cinchona alkaloid derivative as catalyst. A triphasic phase-transfer catalysis protocol has also been developed. p-Peptides have been used as catalysts in this reaction. ... 

A variation of the Sharpless asymmetric epoxidation is to employ chiral hydroperoxides. The chiral iminium salt 89 has moderate enantiocontrol for epoxidation. Quatemized cinchona alkaloids can serve as chiral catalyst and phase-transfer agents in epoxidation of enones with NaOCl. Enones are also epoxidized by oxygen in the presence of diethylzinc and A-methylpseudoephedrine, whereas IZj-enones are submitted to enantioselective epoxidation by t-BuOOH-O-PrO),Yb and the BINOL 90. 

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. 

The use of optically resolved PTC catalysts for the synthesis of enantiomerically pure compounds is no doubt an attractive field. Asymmetric PTC has become an important tool for both laboratory syntheses and industrial productions of enantiomerically enriched compounds. Recently, Lygo and coworkers [207-216] reported a new class of Cinchona alkaloid-derived quaternary ammonium PTC catalysts, which have been applied successfully in the enantioselective synthesis of a-amino acids, bis-a-amino acids, and bis-a-amino acid esters via alkylation [207-213] and in the asymmetric epoxidation of a/p-unsaturated ketones [214-216]. 

Reaction with alkaline peroxide (or hypochlorite) and a chiral catalyst allows the asymmetric epoxidation of enones. Excellent asymmetric induction has been achieved using metal-chiral ligand complexes, such as those derived from lanthanides and (/ )- or (5)-BlNOL. Alternatively, phase-transfer catalysis using ammonium salt derivatives of Cinchona alkaloids, or the use of polyanuno acid... 

Another class of reaction for which chiral tertiary amines are privileged catalysts is the Morita-Baylis-Hillman type (477, 478). One of the first applications of Cinchona alkaloids to mediate an asymmetric Morita-Baylis-Hillman reaction in a natural product synthesis was reported by Hatakeyama et al. in 2001 (479). Using a stoichiometric amount of (3-isocupreidine (568), a stereoselective addition of hexafluoroisopropyl acrylate (569) to aldehyde 570 could be carried out in good yield and with excellent selectivity (99% ee) (Scheme 119). The chiral p-hydroxy ester 571 was converted further into the epoxide 572, a known intermediate in the synthesis of epopromycin B (573). Epopromycin B (573) is a plant cell wall... 

Other Quaternary Ammonium Salts In order to understand the role of the quinoline nucleus on the dnchona alkaloid-derived quaternary ammonium salts in asymmetric PTC, Dehmlow and coworkers replaced the quinoline residue with various sterically bulky aromatic groups. It is interesting that, in the asymmetric epoxidation reaction, the monodea2acinchona alkaloid derivative 56 could provide a higher enantioselectivity than the corresponding cinchona-based catalyst (Figure 12.13) [89]. 

In the presence of cinchona derivatives as catalysts, peroxides or hypochlorites as Michael donors react with electron-deficient olefins to give epoxides via conjugate addition-intramolecular cyclization sequence reactions. Two complementary methodologies have been developed for the asymmetric epoxidation of electron-poor olefins, in which either cinchona-based phase-transfer catalysts or 9-amino-9(deoxy)-epi-dnchona alkaloids are used as organocatalysts. Mechanistically, in these two... 

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