Absolute configuration kinetic studies

From the examples cited above, it is evident that a great deal of research remains to be done on the chiral-amine-catalyzed Michael reaction. All mechanistic proposals have been based solely on knowledge of the absolute configuration of the products, while kinetic data as well as steric factors have not been carefully delineated. Since the research thus far has been restricted entirely to products in which just one chiral center is formed, it is clear that there is no lack of problems to be studied. 

Menthyl p-iodobenzenesulfinate 62 exists in two diastereomeric forms having [a]u + 46 and -146 (79,103). Herbrandson and Cusano (103) determined their absolute configurations on the basis of kinetic studies of the hydrogen chloride-catalyzed equilibration (+>62 (-)-62 and ethanolysis of both diastereomeric esters. They found that the equilibration reaction carried out in nitrobenzene at room temperature results in the formation of a mixture containing 59 3% of the dextrorotatory diastereomer. On the other hand, the rate of ethanolysis of the thermodynamically more stable (+)-62 isomer was found to be twice as large as that of the (->isomer. 

Olefin polymerization using heterogeneous catalysts is a very important reaction and stereochemical aspects have been studied extensively. For a review on this topic see Pino et al. [9], Briefly, the origin of stereoregularity in polyolefins (47) is explained by the chiral nature of the acdve site during polymerization. If the absolute configuration of the first intermediate can be controlled by chiral premodification then we should obtain a non-racemic mixture of R - and "S"-chains. This has indeed been observed e.g. with catalyst M4 for the polymerization (partial kinetic resolution) of racemic 3,7-dimethyl-l-octene (ee 37%) and also for the racemic monomer 46 using Cd-tartate M5. 

We have simulated the steric course of the alkaline hydrolysis of chiral five- (12) and six- (13) membered cyclic phosphonium salts, whose reaction kinetics and product stereochemistries had been studied previously by Marsi and coworkers (14,15). For this purpose, we determined the absolute configuration of the phospholan-ium iodide (12), and the x-ray structures of the related phos-thorinanium salts, 4 and (13). 

Enzymic kinetic resolution of racemic l-arylpropan-2-ols preceded their ZnCl2-catalysed cyclisation to optically pure 3-methylisochromans by treatment with chloromethyl methyl ether (Scheme 20). Conversion to dihydroisocoumarins has been achieved through C-l oxidation. A detailed CD study of these O-hctcrocycles has allowed the determination of their absolute configurations <07EJO296>. 

Tertiary phosphines, in the absence of special effects 2 ), have relatively high barriers 8) ca. 30-35 kcal/mol) to pyramidal inversion, and may therefore be prepared in otically stable form. Methods for synthesis of optically active phosphines include cathodic reduction or base-catalyzed hydrolysis 3° 31) of optically active phosphonium salts, reduction of optically active phosphine oxides with silane hydrides 32), and kinetic 3 0 or direct 33) resolution. The ready availability of optically pure phosphine oxides of known absolute configuration by the Grignard method (see Sect. 2.1) led to a study 3 ) of a convenient, general, and stereospecific method for their reduction, thus providing a combined methodology for preparation of phosphines of known chirality and of high enantiomeric purity. 

The absolute configurations of chelidonine, chelidonine acetate, and norchelidonine have been independently studied by application of a kinetic method of partial resolution during esterification with a-phenylbutyric anhydride, by CD analysis (662), and by H NMR analysis (785). The mass spectra and the NMR spectra of chelirubine, chelilutine, sanguinarine, and sanguilutine have been reported (770, 786). 

The stereochemical similarity between the additive and the crystal structure of one of the enantiomorphic substrates was found to be of paramount importance [8], while parameters like temperature, concentration or nature of the medium had only a quantitative effect on the induction in this system. Further kinetic and mechanistic studies resulted in the formulation of a mechanism according to which the additive is enantioselectively adsorbed in small amounts at the surface of the growing crystal of the same absolute configuration. The adsorption of the chiral additive causes a drastic decrease in the rate of growth of this same crystal, thus shifting the crystallization equilibrium towards the unaffected enantiomorphous phase. This is illustrated in Scheme 2, where the achiral monomer is represented as a fast racemizing... 

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