How To Determine R and S Configurations On A Fischer Projection

Determining R and S Configurations On Fischer Projections

From time to time you may be asked to determine R/S on a Fischer projection.

So how do you do that?

The Fischer projection is an early solution to the problem of drawing 3-dimensional molecules on a 2-dimensional page. Think of a light source illuminating a 3-dimensional object that casts a shadow on a flat surface. If these objects are always arranged in a consistent way, we can infer the 3-D structure of the object from the shadow. In the days before dashes, wedges, and the CIP rules, that’s what Fischer was going for.

[Note: This post was co-authored with Matthew Pierce of Organic Chemistry Solutions.  Ask Matt about scheduling an online tutoring session here. ]

Table of Contents

1. Interpreting A Fischer Projection
2. Step 1: Identify The Chiral Centers
3. Assign Cahn-Ingold-Prelog (CIP) Priorities On The Fischer Projection
4. Trace A Path From The 1, 2, and 3 Priority Groups. Clockwise or Counterclockwise?
5. How Do We Assign R/S When The Priority #4 Group Is In The Front? 
6. With Fischer Projections, “Reverse Rules” Will Apply 99% Of The Time
7. Converting A Fischer Projection To A Line Diagram
8. Summary: Determining R/S On A Fischer Projection
9. Notes

1. Interpreting A Fischer Projection

Recall how the Fischer projection works. The longest carbon chain is arranged vertically and the substituents are drawn out to the side. Although the “projection” is drawn flat, it’s important to remember that the carbons are still tetrahedral. The convention is that the horizontal groups on the side are “wedges” – that is, as my teacher Professor Kazlauskas used to say, “the arms come out to hug you”. Or strangle you, as one of my students once suggested.

How do you determine R/S on a Fischer? Let’s use the first molecule (a) as an example.

2. Identify The Chiral Centers On The Fischer Projection

• The first thing to do, as always, is to identify the chiral centers. Look for carbons attached to four different groups.
• Next, it will likely help to draw out the side groups as wedges.

Don’t worry about putting in dashes for the groups that point up and down. Their stereochemistry is implied by drawing out the side groups as wedges.

3. Assign Cahn-Ingold-Prelog (CIP) Priorities

The next step is to assign priorities.  [see post: Introduction to Assigning R and S – The Cahn Ingold Prelog Rules]

It’s very straightforward when the four groups are different atoms. However, for cases when the atoms directly attached to the chiral center are identical, we’ve seen that it can be helpful to apply the “method of dots” to break ties.  [see post: Assigning Cahn-Ingold-Prelog (CIP) Priorities – The Method of Dots” 

Here, in Round 2, (Br, H, H ) beats (O, O, O) since Br has a higher atomic number than O. (Where’d we get that “third oxygen” ? The C-O pi bond makes O a “phantom atom” for nomenclature purposes.)

4. Now Trace A Path From Priorities 1-2-3 To Determine R or S.

Recall that the Cahn-Ingold-Prelog (CIP) rules for determining R and S configurations outline a set of rules for assigning priorities (1, 2, 3, and 4) to each of the groups assigned to a chiral center.

With the #4 ranked substituent pointing “in the back”, we trace the path from the groups ranked #1, #2, and #3. If that path is clockwise, the chiral center is R. If the path is counter-clockwise, the chiral center is S. 

However, many Fischer projections are not drawn so helpfully with the #4 group in the back.

5. What do you do when #4 is in the front?

When #4 is in the front, one option is to rotate the molecule so as to put #4 in the back. This is a bad option IMO, because it’s too easy to make a mistake.

A better option, as we’ve discussed in the Single Swap Rule, is to remember that determining R/S when #4 is in the front is equivalent to determining R/S on the mirror image of the chiral center. 

[When you look at your left hand in the mirror, it looks like your right hand. You use a “reverse rule” to remind yourself that your left hand is flipped in the mirror and is actually your right hand. Here, we do the same thing!]

• Therefore if 1,2 and 3 go “clockwise” (CW) when #4 is in the front,  then the true configuration is actually S, not R! 
• And if 1, 2 and 3 go “counterclockwise” (CCW) when #4 is in the front, then the true configuration is actually R, not S!

So when #4 is in the front, determine the direction in which priorities #1, #2, and #3 go, and then “flip” the result.

6. With Fischer Projections, “Reverse Rules” Apply Most Of The Time

Let’s go through the next two examples, a little more quickly. Assigning priorities to each of the two chiral centers in questions 2 and 3, we get 2S, 3R for question #2 and 2S, 3S for question #3.

How did we get these priorities? See Note 1 for a walkthrough of Question #2.

There is a useful shortcut here that comes up particularly with sugars.

For a sugar drawn in a Fischer projection with the most oxidized group at the top (i.e. a carboxylic acid or aldehyde), a chiral center with OH on the right will be R, and a chiral center with OH on the left will be S.

This makes assigning R and S to sugars in the Fischer projection a very quick process.

Be more careful with non-sugar molecules, however – one bromine atom on the bottom of the molecule is enough to throw it off.

7. Converting A Fischer Projection To A Line Diagram

Matt sends us this helpful hint on converting Fischer projections to line diagrams which works best for Fischer projections with 2, 3, or 4 carbons.

First, draw in the real shape with wedges and dashes:

Next, we’re going to pretend to “rotate” this Fischer projection either to the left or to the right.

Imagine looking down from the ceiling on someone sleeping on their back with the arms out to hug you.  If they roll over to their “right side”, we’d get the following:

The groups on the right side on the Fischer end up as wedges, and the groups on the left side of the Fischer end up as dashes.

That looks a lot more like a typical line diagram!

Now imagine the same person rolling over onto their “left side”. We’d get this:

Here, the groups on the right side of the Fischer end up as dashes, and the groups on the left side of the Fischer end up as wedges.

Note that in both cases, groups A and B end up being in the plane of the page.

There are limits to this method; once you get past 4 stereocenters it gets unwieldy. But it’s very useful for small Fischer projections. {Thanks to Matt Pierce for his work on this post. [Ask Matt about scheduling an online tutoring session here. ]

8. Summary: Converting A Fischer Projection To A Line Diagram

Determining R/S on a Fischer projection isn’t too hard once you remember that “the arms come out to hug you”, and that the #4 priority group is almost always “in the front”. Just remember to apply the “reverse rules”.

Notes

Note 1. Here’s a walkthrough of how priorities were determined for question #2.