Stereoselective synthesis

The application of molecular mechanics to enantio- and diastereo-selective synthesis is less straight-forward, and publications in this area have only started to appear recently. In the case of the racemate separations described above, the isomer abundances of equilibrated solutions are taken to be related to the energy of all local minima. In contrast, in order to predict the enantiomeric excesses arising from chiral syntheses, the reaction mechanisms and the structures of relevant intermediates or transition states have to be known since their relative energies need to be calculated in order to predict the enantiomeric excesses. Thus, it is to be expected that quantum-mechanical methods such as DFT, in conjunction with molecular mechanics will provide the best insights into enantioselectivity[2391 (see also Section 2.2). 

Various aspects of molecular mechanics of organometallic compounds are discussed in Chapter 14. 

Molecular mechanics was also used to model enantioselective metal-carbene transformations catalyzed by chiral dirhodium(II) compounds[243]. Here, a considerably more thorough approach was used, and the experimental structures of the catalysts were accurately reproduced. A difficulty encountered in this study was the parameterization of the metal-carbene intermediate. This might be part of the reason why in some cases the predicted enantioselectivities were opposite to those observed1 431. 

Metal-n-allyl complexes are important in a number of stereoselective catalytic reactions and therefore represent an interesting challenge to computational chemists (see also Section 14.2). An empirical force field study, based on the MM2 parameterization scheme, aimed at predicting stereoselective nickel(0)-catalyzed cycloadditions, was recently conducted[244]. As in a similar study[24 where a force field for the structure optimization of palladium allyl systems was developed, dummy atoms were needed to define the structural model. A significant im- 

Metal ion-directed stereoselective syntheses also often involve organometallic complexes. While, in terms of a molecular-mechanics description of the structures, there is no fundamental difference between metal-carbon and metal-heteroatom bonds, modeling 7t-bonded ligands is not trivial. Given a known reaction mechanism 

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Stereoselective synthesis of epoxides andaziridines viaylide routes 99PAC369. 

Stereoselective Synthesis - A Practical Approach Second, Thoroughly Revised and Updated Edition With a Foreword by A. I. Meyers 

The stereoselective synthesis of y-bisabolenes was made possible by the development of a new method for the carbosilylation and double alkylation of an acetylenic function coupled with ring closure, overall addition of three carbon substituents to two acetylenic carbons. 

The stereoselective synthesis ofruin -fi-amino-ct-hydroxy acid derivadves using nucleophilic epoxidadon of Tarydthio-Tnitroalkenes has been reported fEq. 4.411."  

Regio- and stereoselective synthesis of y-alkylidenebutenolides and related compounds 97T6707. 

Strategies for stereoselective synthesis of molecules with remote stereoge-nic centers across a double bond of fixed configuration in particular, for synthesis of heterocycles, especially unsaturated macrocyclic lactones 99JCS(P1)1899. 

R. S. Atkinson, Stereoselective Synthesis, John Wiley Sons, New York, 1995. 

For the purpose of stereoselective synthesis the selective elimination at the stage of the /3-hydroxysilane 5 is not a problem the diastereoselective preparation of the desired /3-hydroxysilane however is generally not possible. This drawback can be circumvented by application of alternative reactions to prepare the /3-hydroxysilane 2 however these methods do not fall into the category of the Peterson reaction. 

HIYAMA - HEATHCOCK Stereoselectiveailylation Stereoselective synthesis o( anti homoaitylic alcohols by Cr promoted atlylation o( aldehydes. 

Despite the progress made in the stereoselective synthesis of (R)-pantothenic acid since the mid-1980s, the commercial chemical synthesis still involves resolution of racemic pantolactone. Recent (ca 1997) synthetic efforts have been directed toward developing a method for enantioselective synthesis of (R)-pantolactone by either chemical or microbial reduction of ketopantolactone. Microbial reduction of ketopantolactone is a promising area for future research. 

Contribution of Prof. D. A. Evans to stereoselective synthesis of heterocycles with C—C bond formation (self-review) 99T8589. 

The concept of transient chirality in stereoselective synthesis of five-membered heterocycles using the retro-Diels-Alder methodology 99CRV1163. Five-member heteryladamantanes 99ZOR183. 

A-Sulfonylimines as useful synthons in stereoselective synthesis of heterocycles 97MI40. 

One of the most efficient methods for the stereoselective synthesis of vinylazir- 

Chiral 4,5-disubstituted oxazolidin-2-ones in stereoselective synthesis of (3-hydroxy-a-amino acids 97G475. 

Darzens reaction can be used to efficiently complete the stereoselective synthesis of a"-substituted epoxy ketones. As an example, Enders and Hett reported a technique for the asymmetric synthesis of a"-silylated a,P-epoxy ketones. Thus, optically active a -silyl a-bromoketone 38 was treated with LDA followed by the addition of benzaldehyde to give a"-silyl epoxyketone 40 in 66% yield with good 

The coupling of alkenylboranes with alkenyl halides is particularly useful for the stereoselective synthesis of conjugated dienes of the four possible double bond isomers[499]. The E and Z forms of vinylboron compounds can be prepared by hydroboration of alkynes and haloalkynes, and their reaction with ( ) or (Z)-vinyl iodides or bromides proceeds without isomerization, and the conjugated dienes of four possible isomeric forms can be prepared in high purity. 

Total syntheses have been reported by E.J. Corey (1978B, 1979). We outline only the stereoselective synthesis of a protected fragment (A) which contains carbon atoms 1—9. This fragment was combined with fragment (B) by a Grignard reaction and cyclized by one of the methods typical for macrolide formation (see p. 146). 

Recently this [2,3]-Wittig rearrangement has received much attention and has been developed into a useful method for the stereoselective synthesis of homoal-lylic alcohols. 

A -0-2-Isocephem-4-carboxylic acid, 1-P-phenoxyacetamido-3-methyl-1 -oxo-synthesis, 1, 430 Isochroman, 1,3-diphenyl-synthesis, 3, 787, 788 Isochroman, 3,4-diphenyI-conformation, 3, 631 Isochroman, 2-methyl-synthesis, 3, 788 Isochroman, 3-phenyl-synthesis, 3, 788 Isochroman, (-)-)-(i )-3-phenyI-stereoselective synthesis, 3, 789 Isochroman-4-carboxylic acid, l-oxo-3-phenyl-synthesis, 3, 860 Isochroman-I,3-diones, 4-acyI-synthesis, 3, 831 Isochromanols dehydration, 3, 767 isochroman synthesis from, 3, 789 Isochroman-1-one, 3-aryl-synthesis, 3, 858, 860 

Conjugated dienes, upon complexation with metal carbonyl complexes, are activated for Friedel-Crafts acylation reaction at the akyhc position. Such reactions are increasingly being used in the stereoselective synthesis of acylated dienes. Friedel-Crafts acetylation of 

The stereochemical outcome of the Michael addition reaction with substituted starting materials depends on the geometry of the a ,/3-unsaturated carbonyl compound as well as the enolate geometry a stereoselective synthesis is possible. " Diastereoselectivity can be achieved if both reactants contain a stereogenic center. The relations are similar to the aldol reaction, and for 

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