Chiral catalysts alkenes

Dipolar cydoadditions are one of the most useful synthetic methods to make stereochemically defined five-membered heterocydes. Although a variety of dia-stereoselective 1,3-dipolar cydoadditions have been well developed, enantioselec-tive versions are still limited [29]. Nitrones are important 1,3-dipoles that have been the target of catalyzed enantioselective reactions [66]. Three different approaches to catalyzed enantioselective reactions have been taken (1) activation of electron-defident alkenes by a chiral Lewis acid [23-26, 32-34, 67], (2) activation of nitrones in the reaction with ketene acetals [30, 31], and (3) coordination of both nitrones and allylic alcohols on a chiral catalyst [20]. Among these approaches, the dipole/HOMO-controlled reactions of electron-deficient alkenes are especially promising because a variety of combinations between chiral Lewis acids and electron-deficient alkenes have been well investigated in the study of catalyzed enantioselective Diels-Alder reactions. Enantioselectivities in catalyzed nitrone cydoadditions sometimes exceed 90% ee, but the efficiency of catalytic loading remains insufficient. 

With this reaction, two new asymmetric centers can be generated in one step from an achiral precursor in moderate to good enantiomeric purity by using a chiral catalyst for oxidation. The Sharpless dihydroxylation has been developed from the earlier y -dihydroxylation of alkenes with osmium tetroxide, which usually led to a racemic mixture. 

Since their first introduction by Brunner and McKervey as chiral catalysts for the asymmetric cyclopropanation of alkenes with diazo compounds, chiral dirhodium tetra(A-arylsulfonylprolinates) complexes have been widely used by Davies,in particular, in the context of these reactions. Therefore, the use of... 

These authors were also able to perform this domino process in an enantioselec-tive fashion using the Rh-proline derivative 6/2-57 (Rh2(S-DOSP)4) as chiral catalyst for the cyclopropanation [202]. Reaction of 2-diazobutenoate 6/2-56 and alkenes 6/2-55 in the presence of the catalyst 6/2-57 led primarily to the cyclopropane derivative... 

Further efficient ligands for the epoxidation of alkenes have been reported by Pozzi, but using PhIO as the oxidant and pyridine V-oxide as an additive in FBS.[7, 51-53] Chiral (salen)Mn complexes have been synthesised, which are soluble in fluorous solvents and active in the epoxidation of a variety of alkenes. The catalysts were of the form shown in Figure 6.14. 

The studies summarized above clearly bear testimony to the significance of Zr-based chiral catalysts in the important field of catalytic asymmetric synthesis. Chiral zircono-cenes promote unique reactions such as enantioselective alkene alkylations, processes that are not effectively catalyzed by any other chiral catalyst class. More recently, since about 1996, an impressive body of work has appeared that involves non-metallocene Zr catalysts. These chiral complexes are readily prepared (often in situ), easily modified, and effect a wide range of enantioselective C—C bond-forming reactions in an efficient manner (e. g. imine alkylations, Mannich reactions, aldol additions). 

Among many other methods for epoxidation of disubstituted E-alkenes, chiral dioxiranes generated in situ from potassium peroxomonosulfate and chiral ketones have appeared to be one of the most efficient. Recently, Wang et /. 2J reported a highly enantioselective epoxidation for disubstituted E-alkenes and trisubstituted alkenes using a d- or L-fructose derived ketone as catalyst and oxone as oxidant (Figure 6.3). 

The alkene (5 mmol) in PhMe (8 ml) is stirred with the W-acyl arylhydroxylamine (0.52 mmol) and the chiral catalyst (0.05 mmol) in aqueous NaOH (33%, l ml) at room temperature for 2.5 h. A further amount (0.05 mmol) of catalyst is added and the mixture stirred for an additional 2 h. The solvent and excess alkene are removed under vacuum and the residue is taken up in Et20 (15 ml). The extract is washed with H20 (3 x 20 ml), dried (Na2S04), and evaporated to yield the aziridine. ( Higher ee is achieved using 9% aqueous NaOH.)... 

Method C ( Bu02H in PhMe (80%, 10 ml) is added with stirring at room temperature to the alkene (15 mmol) and W-benzylquininium chloride (0.5 g, 1.1 mmol) in PhMe (10 ml). The mixture is stirred for 5 h, Et20 (25 ml) is added, and the mixture is extracted with H20 (4 x 50 ml). The dried (MgS04) organic phase is evaporated to yield the oxirane. Method D Aqueous NaOCl (115 g, 1.2 ml) is added to the alkene (1 mmol) and chiral catalyst (0.1 mmol) in PhMe (10 ml) at 250 C. The mixture is stirred for 24-48h and H20 (5 ml) is then added. The aqueous phase is separated, extracted with EtOAc (10 ml), and the combined organic solutions are dried (Na2S04) and evaporated to yield the chiral oxirane. 

Oxidative amination of carbamates, sulfamates, and sulfonamides has broad utility for the preparation of value-added heterocyclic structures. Both dimeric rhodium complexes and ruthenium porphyrins are effective catalysts for saturated C-H bond functionalization, affording products in high yields and with excellent chemo-, regio-, and diastereocontrol. Initial efforts to develop these methods into practical asymmetric processes give promise that such achievements will someday be realized. Alkene aziridina-tion using sulfamates and sulfonamides has witnessed dramatic improvement with the advent of protocols that obviate use of capricious iminoiodinanes. Complexes of rhodium, ruthenium, and copper all enjoy application in this context and will continue to evolve as both achiral and chiral catalysts for aziridine synthesis. The invention of new methods for the selective and efficient intermolecular amination of saturated C-H bonds still stands, however, as one of the great challenges. 

As with the Diels-Alder reaction, it is possible to achieve enantioselective cycloaddition in the presence of chiral catalysts.89 The Ti(IV) catalyst C with chiral diol ligands leads to moderate to high enantioselectivity in nitrone-alkene cycloadditions.90... 

Chiral dioxiranes, generated in situ from chiral ketones and Oxone , are promising reagents for the asymmetric epoxidation of unfunctionalized alkenes. Chiral ketone catalysts that are easily accessible in both enantiomers are targets for development. 

Preparation of nonracemic epoxides has been extensively studied in recent years since these compounds represent useful building blocks in stereoselective synthesis, and the epoxide functionality constitutes the essential framework of various namrally occurring and biologically active compounds. The enantiomericaUy enriched a-fluorotropinone was anchored onto amorphous KG-60 silica (Figure 6.6) this supported chiral catalyst (KG-60-FT ) promoted the stereoselective epoxidation of several trans- and trisubstituted alkenes with ees up to 80% and was perfectly reusable with the same performance for at least three catalytic cycles. 

In order to place later chapters in proper context, the first chapter offers a comprehensive overview of industrially important catalysts for oxidation and reduction reactions. Chapters 2 and 3 describe the preparation of chiral materials by way of the asymmetric reduction of alkenes and ketones respectively. These two areas have enjoyed a significant amount of attention in recent years. Optically active amines can be prepared by imine reduction using chiral catalysts, as featured in Chapter 4, which also discloses a novel reductive amination protocol. 

F. Stereoselective Cyclopropanation of Alkenes using Chiral Catalysts. 279... 

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