Olefins, enantioselective epoxidation

Enantioselective Oxidation of Olefins Enantioselective Epoxidation and Enantioselective Dihydroj lation... 

In 1990, Jacobsen and subsequently Katsuki independently communicated that chiral Mn(III)salen complexes are effective catalysts for the enantioselective epoxidation of unfunctionalized olefins. For the first time, high enantioselectivities were attainable for the epoxidation of unfunctionalized olefins using a readily available and inexpensive chiral catalyst. In addition, the reaction was one of the first transition metal-catalyzed... 

Asymmetric epoxidation of olefins with ruthenium catalysts based either on chiral porphyrins or on pyridine-2,6-bisoxazoline (pybox) ligands has been reported (Scheme 6.21). Berkessel et al. reported that catalysts 27 and 28 were efficient catalysts for the enantioselective epoxidation of aryl-substituted olefins (Table 6.10) [139]. Enantioselectivities of up to 83% were obtained in the epoxidation of 1,2-dihydronaphthalene with catalyst 28 and 2,6-DCPNO. Simple olefins such as oct-l-ene reacted poorly and gave epoxides with low enantioselectivity. The use of pybox ligands in ruthenium-catalyzed asymmetric epoxidations was first reported by Nishiyama et al., who used catalyst 30 in combination with iodosyl benzene, bisacetoxyiodo benzene [PhI(OAc)2], or TBHP for the oxidation of trons-stilbene [140], In their best result, with PhI(OAc)2 as oxidant, they obtained trons-stilbene oxide in 80% yield and with 63% ee. More recently, Beller and coworkers have reexamined this catalytic system, finding that asymmetric epoxidations could be perfonned with ruthenium catalysts 29 and 30 and 30% aqueous hydrogen peroxide (Table 6.11) [141]. Development of the pybox ligand provided ruthenium complex 31, which turned out to be the most efficient catalyst for asymmetric... 

A chiral diphosphine ligand was bound to silica via carbamate links and was used for enantioselective hydrogenation.178 The activity of the neutral catalyst decreased when the loading was increased. It clearly indicates the formation of catalytically inactive chlorine-bridged dimers. At the same time, the cationic diphosphine-Rh catalysts had no tendency to interact with each other (site isolation).179 New cross-linked chiral transition-metal-complexing polymers were used for the chemo- and enantioselective epoxidation of olefins.180... 

Catalytic Enantioselective Epoxidation of Simple Olefins by Salen Complexes... 

Anomeric hydroperoxides are readily prepared by treatment of 2-deoxy sugars with H202 in the presence of acid (Fig. 59). They are used as reagents for enantioselective epoxidation of a,(Tunsaturated olefins (e.g. chalcone) in the presence of sodium hydroxide, the epoxidations showed exceptionally high asymmetric induction.76... 

Optically active epoxides are important building blocks in asymmetric synthesis of natural products and biologically active compounds. Therefore, enantio-selective epoxidation of olefins has been a subject of intensive research in the last years. The Sharpless [56] and Jacobsen [129] epoxidations are, to date, the most efficient metal-catalyzed asymmetric oxidation of olefins with broad synthetic scope. Oxidative enzymes have also been successfully utilized for the synthesis of optically active epoxides. Among the peroxidases, only CPO accepts a broad spectrum of olefinic substrates for enantioselective epoxidation (Eq. 6), as shown in Table 8. 

Alkyl-substituted olefins are also epoxidized by CPO. The oxidation of functionalized terminal olefins by CPO catalysis with fBuOOH as oxygen donor affords the corresponding epoxides in good ee values (entries 20, 22, 24-26). While cz5-substituted olefins were epoxidized by CPO with H2O2 in good to excellent enantiomeric excesses (entries 32-35), the trans compounds were poorly converted. The enantioselective CPO-catalyzed epoxidation has been intensively investigated, although examples of diastereoselective oxidations (entries 43-45) are rare. 

In the presence of a catalytic amount of the optically active Mn(III)-saIen complexes 23 and 24, the enantioselective epoxidation of unfunctionalized olefins with the combined use of molecular oxygen and pivaMdehyde was demonstrated. This report revealed that the tert-butyl group on the C3 position of salicylaldehyde in the chiral ligand was essential to realize a high enantioselection, and that pivalaldehyde was the most effective reductant for both the enantioselectivity and chemical yield. It should be noted that the sence of enantioselectivity to form the epoxide from 1,2-... 

In addition to the enantioselective epoxidation of trans- and trisnbstitnted olefins, efforts have also been made for the asymmetric epoxidation of cis- and terminal olefins. Glncose-derived ketone 55 was reported to be a highly enantioselective catalyst for the epoxidation of varions cw-olefins and certain terminal olefins (Fig. 11, Table 4) [97-100]. The resnlts of epoxidation with ketone 55 indicate that a n... 

The enantioselective epoxidation of olefins has received much attention since the corresponding chiral epoxides have become important building units for the... 

Goncalves et have compared the amine (V) and the iminium salt (W) for the enantioselective epoxidation of some prochiral olefins in acetonitrile/water and found that the yields and ees are nearly the same for the epoxidation of a selection of olefins. The amines of type (X) are less well developed. Armstrong has summarized the developments in this field and suggested mechanisms based on hydrogen bonded species, one of which is shown in Figure 1.49. Typical yield and ee data for the epoxidation of 1-phenylcyclohexene for these catalysts are also shown in Figure 1.49. 

ENANTIOSELECTIVE epoxidation of OLEFINS USING PHASE TRANSFER CONDITIONS AND... 

ENANTIOSELECTIVE EPOXIDATION OF OLEFINS USING PHASE TRANSFER CONDITIONS AND A CHIRAL [AZEPINIUM][TRISPHAT] SALT AS CATALYST... 

The enantioselective epoxidation using [diphenylazepinium] [TRISPHAT] salts as catalysts is an easily reproducible procedure that requires no particular precautions except in the handling of Oxone . Although moderate levels of enantiomeric excess are observed, this reaction can be applied to a wide range of olefins, and both enantiomers of the catalyst are readily available through the use of the S) or (R) enantiomers of 3,3-dimethylbutan-2-amine. The results of a small screen using [6-A-((5)-3,3-dimethylbutan-2-yl)-5/7-dibenz[c,e]azepinium][rac-TRISPHAT] salt as catalyst are reported in Table 6.1... 

Table 6.11 Enantioselective epoxidation of olefins 1 to 5 in the presence of [6-N-((S)-3,3-dimethylbutan-2-yl)-5/f-dibenz[c,e]azepinium][rac-TRISPHAT] as catalyst."...

The catalytic asymmetric epoxidation of electron-deficient olefins, particularly a,P-unsaturated ketones, has been the subject of numerous investigations, and as a result a number of useful methodologies have been elaborated [44], Among these, the method utilizing chiral phase-transfer catalysis occupies a unique position in terms of its practical advantages. Moreover, it also allows the highly enantioselective epoxidation of trans-a,P-unsaturated ketones, particularly chalcone. 

Similar to di-olefins, the epoxidation of styrenes with ketone 16 proceeds mainly through transition state spiro G. One difference for styrenes is that planar transition state I could also be competing (R = H) in addition to spiro H, whereas the corresponding planar I for d.v-olefins would be less competitive because of the steric effect (Figure 10.7). As a result, the enantioselectivities obtained for di-olefins with 16 are usually higher than styrenes.74-75 Reducing the competition from planar I would be important to further improve the enantioselectivity for terminal olefins. 

Ketone 1 is highly general and enantioselective for the epoxidation of fran.v-substituted and trisub-stituted olefins. Its ready availability and predictability potentially make this ketone useful. Its utilization in synthesis has been reported by other researchers.79 100 For example, Corey and coworkers have reported that pentaoxacyclic compound 24 can be obtained in 31% overall yield by enantioselective epoxidation of (f )-2,3-dihydroxy-2,3-dihydrosqualene (22) and subsequent cyclization of pentaepoxide 23 (Scheme 10.7).82 Eli Lilly has also used the epoxidation to introduce the epoxide on the sidechain of Cryptophycin 52 (Scheme 10.8).90 The epoxidation has been carried out at multi-kilogram scale at DSM-Catalytica. Around 100 kg of lactone 29 was prepared by the epoxidation of olefin 27 and subsequent in situ cyclization of epoxide 28 (Scheme 10.9).101... 

The Jacobsen-Katsuki Schiff base Mn complexes (6a and 6b) are the most advanced catalysts for enantioselective epoxidation of double bonds. With the typical reactants, cis disubstituted and trisubstituted aromatic olefins, ee values up to 98% are achieved, even if the total number of turnovers is quite limited. In Jacobsen s complex 6a, particularly the bulky /-butyl substituents at positions 3 and 5 of the aromatic ring are crucial in directing the reactant and obtaining high ee values (86). 

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