Adjacent stereocenters

During the course of the conversion of intermediate 18 into intermediate 16, the imposing ferf-butyl substituent at C-8 guides the formation of the adjacent stereocenter at C-9 and it is now called upon to guide, or at least influence in a favorable way, the stereo-... 

Epoxidation of conjugated dienes can be regioselective when one double bond is more electron-rich than the other otherwise mixtures of mono- and diepoxides will be obtained. When the alkene contains an adjacent stereocenter, the epoxidation can be diastereoselective [2]. Hydroxy groups can function as directing groups, causing the epoxidation to take place syn to the alcohol [2, 3]. 

Homoallylamines of type 4 contain two adjacent stereocenters therefore, two diastereomers, s.V)i-5 and anti-6, can be produced. 

Erythro/threo Terms derived from carbohydrate nomenclature used to describe the relative configuration at adjacent stereocenters. Erythro refers to a configuration with identical or similar substituents on the same side of the vertical chain in Fischer projection. Conversely, a threo isomer has these substituents on opposite sides. These terms came from the nomenclature of two carbohydrate compounds, threose and erythrose (see Fig. 1-35). 

The acyclic precursor is an oc, 3-unsaturated amido aldehyde that was condensed with iV-methylhydroxylamine to generate the nitrone ( )-48, which then underwent a spontaneous cycloaddition with the alkene to afford the 5,5-ring system of the isoxazolidinyl lactam 47. The observed product arises via the ( )-nitrone transition state A [or the (Z)-nitrone equivalent] in which the position of the benzyl group ot to the nitrone effectively controls the two adjacent stereocenters while a third stereocenter is predicted from the alkene geometry. Both transition states maintain the benzyl auxiliary in an equatorial position and thus avoid the unfavorable 1,3-diaxial interaction with the nitrone methyl or oxygen found in transition state B. Semiempirical PM3 calculations confirm the extra stability, predicting exclusive formation of the observed product 47. Related cycloadducts from the intramolecular reaction of nitrones containing ester- rather than amide-tethered alkene functionality are also known (83-85). 

The highest diastereomeric ratios were exhibited by 4-methyl-3-heptanol, after construction of two adjacent stereocenters. Both enantiomers of each boronic ester and all four diastereomers of 4-methyl-3-heptanol were made. One or the other or possibly both diastereomeric ratios in this sequence must exceed 99.9 0.1. However, for (3S,4R)-4-methyl-3-heptanol, the achieved diastereomeric ratio was only >99.4 0.6. An unidentified error in procedure was postulated as the cause. 

Allylzincation of alkenylmetals provides a useful entry to the diastereoselective synthesis of sp3 yem-dirnclallic species that can react with two different electrophiles in a one-pot protocol, leading to elaborated acyclic structures with control of the configuration of up to three adjacent stereocenters, as well as to cyclopropanes bearing various substitution patterns126,163. 

The synthesis of a -amino allylic alcohols is particularly difficult, yet this functionality is important in natural products (such as sphingosine) or as a synthon for further elaboration to amino sugars. In synthetic studies of this moiety204, the corresponding enones, with adjacent stereocenters, have been efficiently reduced to the allylic alcohol in quantitative yields and in both a regiocontrolled (1,2) and a stereocontrolled fashion (equation 53). The syn anti ratio of the product depends upon the hydride reductant and solvent being utilized. A 4 1 ratio was obtained with L-selectride and a 1 6 ratio obtained by the use of DIBAL in toluene. 

A highly stereoselective kinetic resolution process for Rh-catalyzed enyne cycloisomerization has also been developed by Zhang et al. [41]. This transformation has enabled the highly enantioselective synthesis of polyfunctionalized tetrahydrofurans and lactones with two or three adjacent stereocenters and it is regarded as a major breakthrough in enynes cycloisomerization and in kinetic resolution (Scheme 7). 

In this chapter, we will review the use of ylides as enantioselective organocata-lysts. Three main types of asymmetric reaction have been achieved using ylides as catalysts, namely epoxidation, aziridination, and cyclopropanation. Each of these will be dealt with in turn. The use of an ylide to achieve these transformations involves the construction of a C-C bond, a three-membered ring, and two new adjacent stereocenters with control of absolute and relative stereochemistry in one step. These are potentially very efficient transformations in the synthetic chemist s arsenal, but they are also challenging ones to control, as we shall see. Sulfur ylides dominate in these types of transformations because they show the best combination of ylide stability [1] with leaving group ability [2] of the onium ion in the intermediate betaine. In addition, the use of nitrogen, selenium and tellurium ylides as catalysts will also be described. 

Finally, it should be pointed out that the configuration of a newly formed stereocenter at the /1-position of the accepting C —C double bond may be controlled by temporarily tethering the incoming 0-nucleophile to an adjacent stereocenter. For example, acid-catalyzed addition of aldehydes or ketones to the hydroxy enone rac-16 resulted in exclusive cw-fusion of the newly formed 1,3-dioxolane ring53. This method could potentially be applied to more complex problems. In any case, exploring its scope should prove worthwhile. 

Radical deoxygenation of an isolated tertiary hydroxy, desirable if involvement of adjacent stereocenters (in alkene formation or rearrangements) has to be avoided, presented problems in derivatization. Scheme 6 shows an inventive solution in which the alcohol (80) was converted to imidate (81). Choice of this electron-rich aromatic system secured smooth thiolysis to (82), which was efficiently deoxyge-... 

The inter- and intramolecular coupling of two carbonyl groups of aldehydes or ketones in the presence of a low-valent titanium species produces a C-C bond with two adjacent stereocenters, a 1,2-diol (a pinacol). These may be further elaborated into ketones by the pinacol rearrangement or be deoxygenated to alkenes (McMurry reaction). 

Meldrum s acid the acyl group originating from the a-amino acid residue is conveniently removed (via 1,2-reduction, dehydration, and 1,4-reduction) by NaBH -HOAc without affecting the adjacent stereocenter. The products are readily converted to y-amino acids. 

The Mukaiyama aldol reaction of ethyl ketones can lead to the controlled introduction of two adjacent stereocenters. While enolate geometry may not be trans-fened faithfully to the relative stereochemistry of the aldol product syn versus anti), stereoconvergent reactions are possible. In the example shown in Scheme 9-5, it should be noted that 7i-facial control from the chiral aldehyde is strong as both products 7 and 8 arise from Felkin selectivity [5]. 

Aldol reactions using chiral auxiliaries are popular as the stereochemical outcome is usually highly predictable and, as such, they provide a reliable method for the incorporation of adjacent stereocenters. The oxazolidinone-based imides 36 and (ent)-36 are the most commonly employed, and these lead to syn aldol products with high levels of stereocontrol [20]. The reaction can be extended to include a variety of a-heteroatom functionality as in 37 (Scheme 9-13) [21]. Numerous examples of the use of these auxiliaries in the synthesis of polypropionate natural products have been reported. Many related auxiliaries are also available and the camphor-based sultam 38 is notable [22]. 

Three possible stereoisomers of lactide (LA) exist d-, l- and me o-lactide (Figure 1). A racemic mixture of d- and L-lactide is referred to as rac-lactide (rac-LA)."° The stereochemistry of these monomers, when incorporated into a polymer chain, creates material with a certain stereocomplexity or tacticity. " The tacticity of a given PLA sample may be defined by two parameters P [probability of forming adjacent stereocenters with the same chirality or a meso (m) linkage] and P [probability of... 

When a quaternary carbon atom is produced in the acylation process, racemization is not possible and the stereochemical outcome can be affected by the presence of an adjacent stereocenter. Treatment of the chiral lactone (168) with LDA and acetyl cyanide gave the diastereomeric products (169) and (170) in the ratio 60 1 (equation 44). ... 

Ester- and amide-substituted radicals bearing an adjacent stereocenter abstract hydrogen with high diastereoselectivity1. The radicals are generated via intra- or intermolecular radical addition to alkenes, halogen abstraction from alkyl halides or reductive cleavage of alkylmercury compounds. Some examples are shown in Table 1. 

Cram s rule (cyclic model) A model for predicting the major stereoisomer resulting from nucleophilic addition to an aldehyde or a ketone having an adjacent stereocenter that is capable of chelation (especially 5-membered ring chelation). After chelate formation, the nucleophile adds from the side opposite the larger of the remaining substituents on the a-stereocenter [48]. See Section 4.2. 

The relative configuration of adjacent substituents in a Fischer projection formula are designated erythro if they are on the same side and threo if they are on the opposite side. The stereochemistry of adjacent stereocenters can also be usefully represented... 

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