Stereochemical control

Figure 3-21. Some reactions that proceed under stereochemical control.

The question of stereochemical control has been a theme running throughout the programme and as you progress to more comphcated molecules it becomes more important. This is very clear from many of the syntheses described in Fleming. 

In some reactions intramolecular chalcogen nitrogen interactions may lead to stereochemical control. For example, selenenyl bromides react with C=C double bonds, providing a convenient method of introducing various functional groups. The reaction proceeds readily, but affords a racemic mixture. The modified reagent 15.22 contains a chiral amine in close interaction with the selenium atom. It reacts with olefins affording up to 97% ee of isomer A (Scheme 15.2). ... 

In the synthesis of polymers it is very important to control the configuration of the multiple stereogenic centers but free radical methods generally fail to give significant stereochemical control (96T(52)4181). To compare the effects of several chiral and achiral auxiliary groups, acrylamides of type 110 were studied. 

Stork and Kahne 108) have demonstrated remarkable stereochemical control in the hydrogenation of a series of cyclohexenols containing allylic... 

This was ihe first investigation of stereoselective formation of geometric isomers of tertiary amines. The authors suggested most enamine systems should be subject to considerable stereochemical control. 

Scheme 11. General strategy for the achievement of stereochemical control in the synthesis of the hexoses 1-8.

A subclass of lyases, involved in amino acid metabolism, utilizes pyridoxal 5-phosphate (PLP, 3-hydroxy-2-methyl-5-[(phosphonooxy)methyl]-4-pyridinecarbaldehyde) as a cofactor for imine/ enamine-type activation. These enzymes are not only an alternative to standard fermentation technology, but also offer a potential entry to nonnatural amino acids. Serine hydroxymethyl-tansferase (SHMT EC 2.1.2.1.) combines glycine as the donor with (tetrahydrofolate activated) formaldehyde to L-serine in an economic yield40, but will also accept a range of other aldehydes to provide /i-hydroxy-a-amino acids with a high degree of both absolute and relative stereochemical control in favor of the L-erythro isomers41. 

Further discussion on the effects of the reaction media and Lewis acids on lacticily appears in Section 7.2. Attempts to control laciicily by template polymerization and by enzyme mediated polymerization are described in Section 7.3. Devising effective means for achieving stereochemical control over propagation in radical polymerization remains an important challenge in the field. 

Stereochemical control at sulfur is detectable only in methyl ds-sulfoxide, of course, but it is noteworthy that the methyl cfs-sulfoxide from 153a is exclusively the less-stable isomer 154-r, t. 

Isobe and coworkers407 found an interesting diastereoselective heteroconjugate addition of methyllithium to 314. The stereochemical control was considered to be determined at the stage of the intermediate 315. Since methyllithium is considered to be coordinated strongly with the methoxyethoxymethoxyl (OMEM) group, the methyl anion would attack the -carbon of the olefin only from one side, as shown below. 

Double asymmetric synthesis and a new strategy for stereochemical control in organic synthesis [95]... 

Therefore, organic solvents have been widely used for biocatalytic reductions. An interesting example for stereochemical control by using organic solvents for... 

Dynamic kinetic resolution of a-alkyl-P-keto ester was conducted successfully using biocatalysts. For example, baker s yeast gave selectively syn(2R, 3S)-product [29a] and the selectivity was enhanced by using selective inhibitor [29b] or heat treatment of the yeast [29c]. Organic solvent was used for stereochemical control of G. candidum [29d]. Plant cell cultures were used for reduction of 2-methyl-3-oxobu-tanoate and afforded antialcohol with Marchantia [29e,f] and syn-isomer with Glycine max [29f]. 

This stereospecific reaction is, therefore, a rare example of stereochemical control by nucleophilic solvent assistance of an ionization process. 

Among the peculiar features of 2-bromoamides there are the following i) possibility of substitution at the tertiary C-Br (RCO2H, RR NH, or a saccharide, as the nucleophiles) ii) chiral stability and stereochemical control at the secondary C-Br atom (RR NH, ROH or a saccharide as the nucleophiles) iii) the presence of bromine allows cyclic voltammetry and electroreduction at controlled potential both of starting compounds and relevant intermediates iv) the Ca polarity can be reversed upon electroreduction, and the resulting Ca enolate forms a C-C bond (CO2 as the electrophile). 

In spite of the fact that biotechnology rather than chemical processing will probably provide the future greatly needed chirally pure compounds (ref. 1), we believe that simple chemical reactions starting from chiral natural compounds and proceeding under stereochemical control will eventually retain full importance. On the above grounds, we report on simple reactions which start from a-aminoacids, as an example of utilization of natural compounds, and move to related bromine containing compounds (Fig. 1). 

A set of works has been recently published, which show the possibility of stereochemical control in the processes of radical additions and telomerization. Photochemical telomerization of bromotrichloromethane with chiral 2,5-dimethyl-pirrolidine acrylamide has been described (ref. 16) ... 

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