Carbonyl catalytic asymmetric epoxidation

Aggarwal et al.108 reported excellent results with the catalytic asymmetric epoxidation of aldehydes. As shown in Scheme 4-52, a series of thioacetals 137 was prepared from hydroxy thiol 136 and the corresponding carbonyl compound. Among them, compound 138, derived from 136 and acetaldehyde, proved to be the best catalyst for asymmetric epoxidation of aldehydes. 

The catalytic asymmetric epoxidation of a,/i-unsaturated carbonyl compounds is one of the synthetically useful reactions in organic synthesis.The resulting chiral epoxides are easily converted to various useful chiral compounds. We developed a new yttrium-(5)-6,6 -[oxybis(ethylene)dioxy]biphenyl-2,2 -diol (1) (Figure 6.10)... 

The explanation for these experimental results, i.e. the lack of label transfer, is that the tetrahedral species (A) resulting from the addition of HSOf to the carbonyl group is capable of epoxidation. Ring closure of (A) is likely to be the rate-determining step in dioxirane formation. This work is important from a synthetic viewpoint, since it is crucial in the development of chiral ketones for the catalytic asymmetric epoxidation and the design of probes of transition state stereoselectivities that the nature of the oxidizing species is understood. 

A general review of the advances in homogeneous and heterogeneous catalytic asymmetric epoxidation covering Sharpless, porphyrin, A, A -bis(saclicylaldehydo)ethylenediamine (salen), and l,T-bi-2-naphthol (BINOL) systems, carbonyl-derived dioxiranes and iminium species, as well as their supported counterparts, has recently been published <2005CRV1603>. 

Catalytic asymmetric epoxidation of a./i-unsaturated carbonyl compounds 02YGK94. 

The temperature required for the formation of diazoalkanes can be significantly decreased by using phase-transfer catalysis. This method has allowed the use of transition metals in the catalytic asymmetric epoxidation of carbonyl compounds (eq 19). The use of phase-transfer catalysis and moderate temperatures promotes the formation of diazoalkanes at a very low rate, achieving low concentrations of diazoalkane during the reaction, which is critical for the outcome of the process. The use of trisylhydrazone has shown better results in some cases compared to its tosyl analog. Presumably, the bulkier sulfonyl group may facilitate the... 

Catalytic asymmetric epoxidation of a -unsaturated carbonyl compounds is an important transformation in organic synthesis [108]. Shibasaki and coworkers... 

From the point of view of synthesis, optically active a -epoxy carbonyl compounds of higher oxidation state, such as esters or amides, are much more useful as chiral building blocks, whereas catalytic asymmetric epoxidation of a -unsaturated esters and amides is difficult owing to lower reactivity than enones [112, 113] The problem was addressed by exploiting the unique reactivity of a -unsaturated N-acylimidazoles and N-acylpyrroles in asymmetric epoxidation with lanthanide... 

A more versatile method to use organic polymers in enantioselective catalysis is to employ these as catalytic supports for chiral ligands. This approach has been primarily applied in reactions as asymmetric hydrogenation of prochiral alkenes, asymmetric reduction of ketone and 1,2-additions to carbonyl groups. Later work has included additional studies dealing with Lewis acid-catalyzed Diels-Alder reactions, asymmetric epoxidation, and asymmetric dihydroxylation reactions. Enantioselective catalysis using polymer-supported catalysts is covered rather recently in a review by Bergbreiter [257],... 

Until 1968, not a single nonenzymic catalytic asymmetric synthesis had been achieved with a yield above 50%. Now, barely 15 years later, no fewer than six types of reactions can be carried out with yields of 75-100% using amino acid catalysts, i.e., catalytic hydrogenation, intramolecular aldol cyclizations, cyanhydrin synthesis, alkylation of carbonyl compounds, hydrosilylation, and epoxidations. 

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... 

In addition to epoxides, three-membered nitrogen heterocycles, aziridines, can be obtained by means of catalytic asymmetric aziridinations (Eq. 30). To this aim, chiral ruthenium(salen) complexes 67 [56] and 68 [57] were useful (Fig. 1). The former phosphine complexes 67 gave the aziridine from two cy-cloalkenes with 19-83% ee [56]. On the other hand, terminal alkenes selectively underwent aziridination in the presence of the latter carbonyl complex 68 with 87-95% ee [57]. In these examples, N-tosyliminophenyliodinane or N-tosyl azide were used as nitrene sources. Quite recently, catalytic intramolecular ami-dation of saturated C-H bonds was achieved by the use of a ruthenium(por-phyrin) complex (Eq. 31) [58]. In the presence of the ruthenium catalyst and 2 equiv iodosobenzene diacetate, sulfamate esters 69 were converted into cyclic sulfamidates 70 in moderate-to-good yields. 

Aggarwal VK, Winn CL. Catalytic, asymmetric sulfur ylide-mediated epoxidation of carbonyl compounds scope, selectivity, and applications in synthesis. Acc. Chem. Res. 2004 37 611-620. Li A-H, Dai L-X, Aggarwal VK. Asymmetric ylide reactions epoxidation, cyclopropanation, aziridination, olefination, and rearrangement. Chem. Rev. 1997 97 2341-2372. 

Scope, selectivity, and applications in the synthesis of catalytic, asymmetric sulfur ylide-mediated epoxidation of carbonyl compounds 04ACR611. 

The Darzens reaction (tandem aldol-intramolecular cyclization sequence reaction) is a powerful complementary approach to epoxidation (see Chapter 5) that can be used for the synthesis of a,P-epoxy carbonyl and a,p-epoxysulfonyl compounds (Scheme 8.32). Currently, all catalytic asymmetric variants of the Darzens reactions are based on chiral phase-transfer catalysis using quaternary ammonium salts as catalysts. 

Despite the number of reports of the asymmetric synthesis of tertiary a-aryl cyclohexanones, there have only been three reports which describe the asymmetric synthesis of tertiary a-aryl cyclopentanones. The first of these was reported by Shi via asymmetric epoxidation of benzylidene cyclobutanes and epoxide rearrangement in a subsequent step [76]. Backvall used a dynamic kinetic resolution of aUyhc alcohols-aUylic substitution-oxidative cleavage sequence to access 2-phenylcyclopentanone [77]. The first direct catalytic asymmetric synthesis of tertiary a-aryl ketones was recently described by Kingsbury using a series of Sc-catalysed diazoalkane-carbonyl homologations with bis/tris oxazohne ligands [78]. 

Discovering highly enantioselective ketone catalysts for asymmetric epoxidation has proven to be a challenging process. As shown in Scheme 3.62, quite a few processes are competing with the catalytic cycle of the ketone mediated epoxidation, including racemization of chiral control elements, excessive hydration of the carbonyl, facile... 

Iminium catalysis has been quite successful for asymmetric epoxidation of a,P-unsaturated carbonyl compounds, particularly, enals. Enones have remained difficult substrates. Recently, List and coworkers reported an enantioselective epoxidation of cyclic enones with either cinchona-based primary amine 38 or a counter-anion catalytic systan 149 combining a chiral vicinal diamine and a chiral phosphoric acid [69], High enantioseleclivities could be achieved in a number of cyclic enones (Scheme 5.40). 

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