Threo enantiomers

Methylphenidate Metabolism. The metabolism and pharmacokinetics of methylphenidate have been studied extensively. Methylphenidate (8)is administered as the racemic threo isomer, but the (-)-threo enantiomer is more rapidly metabolized. 

Dexmethylphenidate (FocaUn) is the rf-threo enantiomer of racemic methylphenidate. It is FDA approved for the treatment of ADHD and is listed as a schedule II controlled substance in the United States. 

In contrast, syn addition of H2 to a trans-alkem forms only the threo enantiomers. Thus the addition of hydrogen is a stereospecific reaction—the product obtained from addition to the cis isomer is different from the product obtained from addition to the trans isomer. It is also a stereoselective reaction because all possible isomers are not formed for example, only the threo enantiomers are formed in the following reaction. 

If two asymmetric carbons are created as the result of an addition reaction that forms a bromonium ion intermediate, only one pair of enantiomers will be formed. In other words, the addition of Bt2 is a stereoselective reaction. The addition of B12 to the cis alkene forms only the threo enantiomers. 

Because the addition of Br2 to the cis alkene forms the threo enantiomers, we know that addition of Br2 is an example of anti addition because if syn addition had occurred to the cis alkene, the erythro enantiomers would have been formed. The addition of Bt2 is anti because the reaction intermediate is a cyclic bromonium ion (Section 4.7). Once the bromonium ion is formed, the bridged bromine atom blocks that side of the ion. As a result, the negatively charged bromide ion must approach from the opposite side (following either the green arrows or the red arrows). Thus, the two bromine atoms add to opposite sides of the double bond. Because only anti addition of Br2 can occur, only two of the four possible stereoisomers are obtained. 

Addition of H2 Addition of borane syn cis > erythro enantiomers trans > threo enantiomers... 

Addition of Br2 anti cis > threo enantiomers trans > erythro enantiomers ... 

Two asymmetric carbons have been created in the product. Because the reactant is cis and addition of Br2 is anti, the threo enantiomers are formed. 

When Br2 adds to an alkene with different substituents on each of the two sp carbons, such as cA-2-heptene, identical amounts of the two threo enantiomers are obtained even though Br is more likely to attack the less sterically hindered carbon atom of the bromo-nium ion. Explain why identical amounts of the stereoisomers are obtained. 

Build two models of trows-2-pentene. To each model, add Br2 to opposite sides of the double bond, adding Br" to the top of the double bond in one model and adding it to the bottom of the double bond in the other model, thereby forming the enantiomers shown on page 283. Rotate the models so they represent Fischer projections. Are they erythro or threo enantiomers Compare your answer with that given on page 283. 

When Fischer projections are drawn for stereoisomers with two adjacent asymmetric centers (such as those for 3-chloro-2-butanol), the enantiomers with the hydrogens on the same side of the carbon chain are called the erythro enantiomers (see Problem 48), whereas those with the hydrogens on opposite sides are called the threo enantiomers. Therefore, 1 and 2 are the erythro enantiomers of 3-chloro-2-butanol (the hydrogens are on the same side), whereas 3 and 4 are the threo enantiomers. 

Because the addition of Br2 to the cis alkene forms the threo enantiomers, we know that anti addition must have occurred, since we have just seen that syn addition would have formed the erythro enantiomers. The addition of Br2 is anti because the two bromine atoms add to opposite sides of the double bond (Figure 6.9). 

Formation of a bromonium ion at the other face of pahnitoleic acid gives a result such that the threo enantiomers are the only products formed (obtained as a racemic modification). 

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