Determining the Configuration of a Stereocenter

Now that we can find stereocenters, we must now learn how to determine whether a stereocenter is R or S. There are two steps involved in making the determination. First, we give each of the four groups a number (from 1 to 4). Then we use the orientation of these numbers to determine the configuration. So, how do we assign numbers to each of the groups  

We start by making a list of the four atoms attached to the stereocenter. Let s look at the following example  

The four atoms attached to the stereocenter are C, C, O, and H. We rank them from 1 to 4 based on atomic number. To do this, we must either consult a periodic table every time or commit to memory a small part of the periodic table—just those atoms that are most commonly used in organic chemistry  

This is how we rank the two carbon atoms for each carbon atom, we write a list of three atoms it is connected to (other than the stereocenter). Let s do the example above to see how this works. The carbon atom on the left side of the stereocenter has four bonds one to the stereocenter, one to another carbon atom, and then two hydrogen atoms. So, other than the stereocenter, it has three bonds (C, H, and H). Now let s look at the carbon atom on the right side of the stereocenter. It has four bonds one to the stereocenter and then three hydrogen atoms. So, other than the stereocenter, it has three bonds (H, H, and H). We compare the two lists and look for the hrst point of difference  

We see the first point of difference immediately carbon beats hydrogen. So the left side of the stereocenter gets priority over the right side, and the numbering turns out like this  

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Now we need to leam how to use this numbering system to determine the configuration of a stereocenter. The idea is simple, but it is difficult to do if you have a hard time closing your eyes and rotating 3D objects in your mind. For those who cannot do this, don t worry. There is a trick. Let s first see how to do it without the trick. 

You might be wondering how you would determine the configuration of a stereocenter when you are given a Fischer projection. If each stereocenter is drawn as two wedges and two dashes, how do you figure out how to look at the stereocenter The answer is simple. Just choose one dash and one wedge, and draw them... 

Notice that Ri is now pointing straight down, and the OH is now on a dash. The configuration has not changed. If you need to convince yourself of this, determine the configuration of that stereocenter in each of two drawings. You will see that it has not changed. 

PROBLEMS For each compound below, determine the configuration of every stereocenter. Then draw the enantiomer of each compound below (the COOH group is a carboxylic acid group). 

SnI and Sn2 reactions produce almost the same products. In both reactions, a leaving group is replaced by a nucleophile. The difference in products between SnI and Sn2 reactions arises when the leaving group is attached to a stereocenter. In this situation, the Sn2 mechanism will invert the stereocenter, while the SnI mechanism will produce a racemic mixture. That s the main difference—the configuration of one stereocenter. It seems like a lot of work to go through to determine the configuration of one stereocenter (which matters only some of the time). 

Asymmetric reactions and processes give rise to two kinds of stereoisomeric products diastereomers and enantiomers. The physical separation of these isomers with simultaneous analysis of isomer distribution (peak integration) is an excellent way to determine the selectivity of a reaction. For the analysis of diastereomers, standard chromatographic techniques suffice, although the chromatographic method should be accompanied by another technique that determines the configuration of the new centers. Diastereomer analysis also ensues in cases of double asymmetric induction, and the configuration of known centers in the reactants may be used as a point of reference for determination of the new stereocenter(s) by NMR or X-ray. 

The following example demonstrates how the absolute configuration of a stereocenter is determined from its Fischer projection. 

Similarly the stereobonds" can be defined and added to the bond list in the fourth column of the CT. A single bond acquires the value of 0 if it is not a "stereobond, 1 for np (a wedged bond). 4 for either up or down, and 6 for down (a basbed bond), The cisjtrans or E[Z configuration of a double bond is determined by the x,y.2 coordinates of the atom block if the value is 0, Tf it is 3, the double bond is either cis or tmns. In the bond block of our example (Figure 2-76), the stereocenter is set to 1 (up) at atom 6 (row 6, column 4 in the bond block), whereas the configurations of the double bonds are determined by the x,y coordinates of the atom block. 

The 1,4-addition of the anion of a racemic /1-oxo sulfoxide to racemic 2-cyclopentenone was reported to give a single diastereomeric adduct resulting from addition opposite to the y-ace-toxy group20, t he relative configuration of the exocyclic stereocenter was not determined. 

More recently, the addition of cyanide ion, generated from TMS cyanide and cesium fluoride, to a-aziridino N-siflfinyl imines, being chiral either at the a position or at sulfur, has been examined [87] (Scheme 28). The configuration of the newly formed stereocenter was determined only by the chiral (S)-sulfinyl group. In fact, the R configuration (diastereomeric excess, de, 98%) was obtained from either the Q -(ii)-imine 186 or the a-(S)-imine 188, giving 187 and 189, respectively. Acyclic 2,3-diaminonitriles can be obtained... 

When we learned how to name compounds, we said that we would skip over the naming of stereocenters until we learned how to determine configuration. Now that we know how to determine whether a stereocenter is R or S, we can now see how to include this in the name of a compound. It is actually quite simple. If there is only one stereocenter, then you simply place either (R) or (S) at the beginning of the name. For example, 2-butanol has one stereocenter, and can either be (I )-2-bu-tanol or (S)-2-butanol, depending on the configuration of the stereocenter. If more than one stereocenter is present, then you must also use numbers to identify the location of each stereocenter. Consider the following example ... 

Owing to the concerted mechanism, chirality at C(3) [or C(4)] leads to enantiospecific formation of new stereogenic centers formed at C(l) [or C(6)].203 These relationships are illustrated in the example below. Both the configuration of the new stereocenter and the new double bond are those expected on the basis of a chairlike TS. Since there are two stereogenic centers, the double bond and the asymmetric carbon, there are four possible stereoisomers of the product. Only two are formed. The Zs-double bond isomer has the 5-con figuration at C(4) and the Z-isomer has the -configuration. These are the products expected for a chair TS. The stereochemistry of the new double bond is determined by the relative stability of the two chair TSs. TS B is less favorable than A because of the axial placement of the larger phenyl substituent. 

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