Stereoselective syntheses

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). 

metal ion directed stereoselective syntheses 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 rc-bonded ligands is not trivial. Given a known reaction mechanism (which is not possible for many catalytic reactions) the main problem is the parameterization of the potential energy functions for the intermediates and transition states. The problem is that force field parameters are generally carefully 

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- 

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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). 

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. 

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... 

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. 

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... 

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

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

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. 

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... 

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. 

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

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

Stereoselective synthesis of epoxides andaziridines viaylide routes 99PAC369. 

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

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

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

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... 

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. 

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. 

Jackson and coworkers have used a new approach to the synthesis of fi-hydtoxy-ct-amino acids using farylthio nitrooxiranes. c-Jsopropylideneglyceraldehyde is converted into the corresponding 1-arylthio-l-nitroalkene, which is a key material for stereoselective synthesis of fi,Y-dihydroxyamino acids fScheme 4.6. The key step is stereoselective nucleophilic epoxlda-donof the Tarylthio-Tnltroalkene. Sy)i and ruin epoxides are selecdvely obtained by appropriate choice of epoxidadon reagent." ... 

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

An expedient and stereoselective synthesis of bicyclic ketone 30 exemplifies the utility and elegance of Corey s new catalytic system (see Scheme 8). Reaction of the (R)-tryptophan-derived oxazaboro-lidine 42 (5 mol %), 5-(benzyloxymethyl)-l,3-cyclopentadiene 26, and 2-bromoacrolein (43) at -78 °C in methylene chloride gives, after eight hours, diastereomeric adducts 44 in a yield of 83 % (95 5 exo.endo diastereoselectivity 96 4 enantioselectivity for the exo isomer). After reaction, the /V-tosyltryptophan can be recovered for reuse. The basic premise is that oxazaborolidine 42 induces the Diels-Alder reaction between intermediates 26 and 43 to proceed through a transition state geometry that maximizes attractive donor-acceptor interactions. Coordination of the dienophile at the face of boron that is cis to the 3-indolylmethyl substituent is thus favored.19d f Treatment of the 95 5 mixture of exo/endo diastereo-mers with 5 mol % aqueous AgNC>3 selectively converts the minor, but more reactive, endo aldehyde diastereomer into water-soluble... 

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

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

As described in Section 2.3.2, vinylaziridines are versatile intermediates for the stereoselective synthesis of (E)-alkene dipeptide isosteres. One of the simplest methods for the synthesis of alkene isosteres such as 242 and 243 via aziridine derivatives of type 240 and 241 (Scheme 2.59) involves the use of chiral anti- and syn-amino alcohols 238 and 239, synthesizable in turn from various chiral amino aldehydes 237. However, when a chiral N-protected amino aldehyde derived from a natural ot-amino acid is treated with an organometallic reagent such as vinylmag-nesium bromide, a mixture of anti- and syn-amino alcohols 238 and 239 is always obtained. Highly stereoselective syntheses of either anti- or syn-amino alcohols 238 or 239, and hence 2,3-trans- or 2,3-as-3-alkyl-2-vinylaziridines 240 or 241, from readily available amino aldehydes 237 had thus hitherto been difficult. Ibuka and coworkers overcame this difficulty by developing an extremely useful epimerization of vinylaziridines. Palladium(0)-catalyzed reactions of 2,3-trons-2-vinylaziri-dines 240 afforded the thermodynamically more stable 2,3-cis isomers 241 predominantly over 240 (241 240 >94 6) through 7i-allylpalladium intermediates, in accordance with ab initio calculations [29]. This epimerization allowed a highly stereoselective synthesis of (E) -alkene dipeptide isosteres 243 with the desired L,L-... 

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