Chlorination enantioselective

This ligand has also been used by the same authors to promote the addition of ZnMe2 to a functionalised a,(3-unsaturated ketone in the asymmetric key step of the first enantioselective synthesis of (-)-frontalin. This synthesis started with the naphthalene-catalysed lithiation of a chlorinated ketal (Scheme 4.15) that, after several transmetalation processes, was trapped by reaction... 

Polymerization of triphenylmethyl methacrylate in the presence of a chiral anion catalyst results in a polymer with a helical structure that can be coated onto macroporous silica [742,804). Enantioselectivity in this case results from insertion and fitting of the analyte into the helical cavity. Aromatic compounds and molecules with a rigid nonplanar structure are often well resolved on this phase. The triphenylmethyl methacrylate polymers are normally used with eluents containing methanol or mixtures of hexane and 2-propanol. The polymers are soluble in aromatic hydrocarbons, chlorinated hydrocarbons and tetrahydrofuran which, therefore, are not suitable eluents. 

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... 

This landmark discovery paved the way for the development of transition metal-catalyzed hydroboration. The conversion of an alkene into an organoborane intermediate has made this a valuable synthetic technique, particularly since the development of enantioselective variants.9,10 They serve as synthons for numerous functional groups11 and are often subjected to a consecutive carbon-oxygen, carbon-carbon, boron-carbon, boron-chlorine, or carbon-nitrogen24 bond-forming reaction (Scheme 3). 

Domino processes can also be performed on open-chain compounds. MacMillan and co-workers demonstrated this with their own imidazolidinone catalysts. Conjugate addition of a nucleophilic heterocycle 231 to the a,(i-unsaturated enal 230 followed by a-chlorination of the resulting enamine led to the syn products 234 in very high enantioselectivities and good sytv.anti diastereoselectivities (Scheme 38) [347]. Similar domino sequences, but with different nucleophile-electrophile partners, were also reported independently by Jprgensen [348]. 

The enzyme recLBADH is the first catalyst that has been found to allow the highly regio- and enantioselective synthesis of 5-hydroxy-P-keto esters by reduction of the respective diketo esters. This enzymatic reaction is of enormous preparative value. The substrates are readily available by acylation of P-keto ester bisenolates and the reaction only requires a simple batch technique which is easy to scale up. Reduction of the chlorinated compound la has been performed routinely on a 75 g scale in our laboratory (8 L fed batch), yielding (S)-2a in an isolated yield of 84% [10]. 

Enantioselective halogenation is a powerful transformation, directly installing an efficient leaving group. Thomas Leckta of Johns Hopkins University has shown (7. Am. Chem. Soc. 2004,126, 4245) that benzoylquinine 11 catalyzes the a-chlorination of ketenes derived from acid chlorides such as 10, to give 12 in high . 

In Communications submitted two weeks apart, David W.C. MacMillan of Caltech (7. Am. Chem. Soc. 2004,126,4108) and Karl Anker Jorgensen of Aarhus University, Denmark (7. Am. Chem. Soc. 2004, /26,4790) reported the enantioselective a-chlorination of aldehydes, using organocatalysts 14 and 15 respectively. The chloro aldehydes are promising precursors to, inter aliay enantiomerically-pure epoxides. 

Hence, in this work, we report the heterogeneization of this new chiral macrocycle onto micelle-templated silicate (MTS) surface by substitution of chlorine atom of previously grafted 3-chloropropyl chain. After A-alkylation of the tetraazamacrocycle with propylene oxide and metalation with Mn(lI)Cl2, the catalytic performance of the corresponding hybrid materials was evaluated in the heterogeneous enantioselective olefin epoxidation. 

Jacobsen and co-workers have reported that chiral diimine 33a serves as an effective chiral auxiliary for the copper-catalyzed aziridination of aryl-substituted Z-olefins (Scheme 6B.35) [80], For example, the aziridination of 6-cyanochromene proceeds with high enantioselectivity (>98% ee). Comparison of ligands 33a-33c has revealed that the o-substituents in the ligands sterically and electronically influence the enantioselectivity of the reaction, that is, the introduction of chlorines at o-positions not only prolongs catalyst lifetime but also enhances enantioselectivity. The reactions of other Z-substrates and cinnamate esters catalyzed by 33a show moderate-to-high enantioselectivity, whereas that of -stilbene gave low enantioselectivity (Table 6B.3). 

As in the case of other CSPs, the chiral resolution on these CSPs is also affected by a change in the structures of the racemic compounds. The different selectiv-ities of amino acids on these CSPs may be considerd as the best example. The effect of structures of the racemates on the chiral resolution may be understood from the work carried out by Shieh et al. [71]. The authors studied the chiral resolution of amino acids as their Schiff s bases. These racemates differ slightly in their structure and the substituent, such as alkyl groups, hence showed different values of enantioselectivities. The values of retention and separation factors decreased by introducing bulky groups in the racemates. Aboul-Enein and Ali [70] observed the lower values of retention factors of miconazole in comparison to econazole and sulconazole. The authors explained this sort of behavior on the basis of the steric effect exerted by the extra chlorine atom in miconazole molecule. 

THF, ethyl acetate, and methanol. In contrast, use of other chlorinated solvents, e.g. CCI4, and cyclohexane resulted in higher enantioselectivity, comparable with that for chloroform. The range of dienophile substrates was also studied. Replacing N-methylmaleimide by N-phenylmaleimide, in the presence of quinidine as a catalyst, also led to a good yield, although enantioselectivity was lower (20% ee compared with 61% ee). Much slower reaction rates were observed when methyl acrylate and methyl fumarate were used and enantioselectivity was low (0% ee for methyl acrylate and 30% ee for methyl fumarate). With methyl maleate as a dienophile no reaction was observed. Mechanistic studies were also conducted by Kagan et al. results were in accordance with a concerted [4+2]-cycloaddition process. 

In the field of asymmetric organocatalytic alkylation (see also Section 3.1) impressive examples with enantioselectivity > 99% ee have been reported by the Corey group, the Park and Jew group, and the Maruoka group [15-17]. Different types of catalyst have been used, with amounts of catalyst in the range 0.2 to 10 mol%. High enantioselectivity (99%) has also been achieved for asymmetric halogenation reactions (see also Section 3.4). This has been demonstrated for chlorination and bromination reactions by Lectka and co-workers [18]. 

Diphenylpyrrolidine (77) catalyses the enantioselective cy-chlorination of aldehydes.299 Mechanistic and computational studies suggest that - in contrast to pre- viously proposed mechanisms involving direct formation of the carbon-electrophile bond - iV-chlorination occurs first, followed by a 1,3-sigmatropic shift of chlorine to the enamine carbon. The product iminium ion is then hydrolysed in the ratedetermining step. 

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