Kinetic Resolutions Combined with Inversions

Another possibility to obtain 100% yield of the enantiopure product is to combine the kinetic resolution with an inversion reaction [25, 35, 36]. In this case an enzymatic hydrolysis is followed by a Mitsunobu inversion. It is, however, in fact a three-step reaction with solvent changes between the reactions. Similarly the sulfatase-catalysed enantios elective inversion of a racemic sulfate yields a homo-chiral mixture of alcohol and sulfate. This yields 100% enantiopure product after a second, acid-catalysed hydrolysis step, which is performed in organic solvent/water mixtures [26]. 

The lipase or esterase-catalysed hydrolyses are straightforward and mild reactions. Consequently they can readily be performed on a large scale and they are suitable for first year undergraduate teaching [37]. Indeed, these enzymes are 

X = COOR, CONHR, CN, OCOR, NHCOR Y = COOH, CONH2,OH, NH2 

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Kinetic Resolutions of Esters Combined with Inversions... 

Instead of starting with racemic starting material it is also possible to use symmetric substrates [25]. The hydrolase selectively catalyses the hydrolysis of just one of the two esters, amides or nitriles, generating an enantiopure product in 100% yield (Scheme 6.7). No recycling is necessary, nor need catalysts be combined, as in the dynamic kinetic resolutions, and no follow-up steps are required, as in the kinetic resolutions plus inversion sequences. Consequently this approach is popular in organic synthesis. Moreover, symmetric diols, diamines and (activated) diacids can be converted selectively into chiral mono-esters and mono-amides if the reaction is performed in dry organic solvents. This application of the reversed hydrolysis reaction expands the scope of this approach even further [22, 24, 27]. 

The kinetic resolution of aziridines has also been reported. Alper showed that the car-bonylation of N-ferf-butyl- and N-adamantyl-2-arylaziridines in the presence of catalytic amounts of the combination of [Rh(COD)Cl]j and enantiopure menthol produced the corresponding N-alkyl-3-phenylazetidin-2-ones in up to 99.5% optical yield, although the isolated yields were modest. Consistent with the cobalt-catalyzed carbonylation of epoxides and related substrates, inversion of configuration occurs at the site of carbonyl insertion. 

Other convenient reagents for the imidation of sulfides and selenides are imidoiodanes such as A-(/>-tolylsulfonyl)-imino(phenyl)iodane (PhI=NTs).304 Unfortunately, these reagents are sometimes difficult to prepare due to their thermal sensitivity and some have even been claimed to be explosive.305 Selenimides are tricoordinate tetravalent compounds and can be isolated in optically active forms. They can be prepared from optically active selenoxides, a reaction which was shown to occur with an overall retention of stereochemistry.306 They can also be obtained by optical resolution of a diastereomeric selenimide and stereochemical issues including kinetics of epimerization by pyramidal inversion were studied in detail.307 Also the enantioselective imidation of prochiral selenides of type 179 is possible by using a combination of A-(/>-tolylsulfonyl)imino(phenyl)iodane (PhI=NTs) and a catalytic amount of... 

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. 

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