A simple trick: The (R)-(S) Toggle

by James

in Organic Chem Study Tips, Organic Chemistry 1, Stereochemistry

1-RS

The difficulty of assigning (R)/(S) to a stereocenter can be highly dependent on the way the molecule is drawn. For example, assigning the stereochemistry of A should be a cakewalk if you are the least bit familiar with the rules, while B  and C are a little more difficult. The thing is, you’re not always going to be given a structure with the 4th ranked substituent in the back. One thing I see students do a lot in this situation is try to redraw the structure to make it easier to assign (R)/(S) While this can be effective, it can easily lead to mistakes. Furthermore, when you’re dealing with cyclic systems like morphine [C], trying to draw the mirror image in a reasonable time frame might induce brain trauma.   [By the way, for B, you remember why the CH2CH2Br group is ranked 3rd, right? [Note 1]]

Instead of redrawing the whole molecule, just leave the hydrogen (or other 4th ranked substituent) in front and figure out whether the substituents ranked 1,2, and 3 go clockwise or counterclockwise. Then toggle (i.e. reverse direction CW to CCW or vice versa) to account for the fact that the 4th ranked substituent is in the front, and assign (R) or (S) based on that.  You end up with the same answer without having to redraw anything.

We also make these types of adjustments when we’re looking in mirrors. If I’m looking in a mirror at you holding out your right hand, I account for the mirror by “flipping” your image to know that you are really holding out your left. It’s the same thing with molecules.

2-RS
This trick seems obvious, but I’ve met enough people who don’t do it to make it worth mentioning. Determining (R)/(S) eventually becomes second nature, as does the ability to flip, rotate and invert chemical structures in your head. Much like London cab drivers, one of the interesting side effects of becoming an organic chemist is that it hyper-develops your brain’s spatial abilities.

[note 1 – Priority is determined at the point of first difference. Hence, of the two carbons attached to the stereocenters, CH2 and C=O, the C=O is given priority [O > H], regardlesss of whether a higher ranked element is further down the second chain. ]

Related Posts:

{ 9 comments… read them below or add one }

mevans

James,

Call me crazy, but the stereocenter in C should be R, right? So much for second nature… :-P

Reply

James

You are not crazy, I’m an idiot. Fixed – Thanks for the correction!

Reply

Michal St

Is there a trick for rotations when the hydrogen (or other fourth ranked substituent ) is in the plane of the page?

Reply

James

Yep – use the single swap rule (a later, improved version of this post). http://masterorganicchemistry.com/2011/01/24/the-single-swap-rule/

Reply

Pavel S.

Hello James,

Thanks for the wonderfully organized website. I had a question about the swap trick –

We were told to visualize molecules in class and the trick is never taught even though the instructor is highly rated and knows it. Could this be because it does not work in all cases?
H
|
C-Cl
Wedge OCH3 Hash CH3
The above is just supposed to be a tetrahedral structure with H pointing up and Cl pointing right (both are in the plane of the page). On the bottom left is an OCH3 with a wedge (coming out of page) and a CH3 on the bottom right with a hash (going into page). The priority is Cl>OCH3>CH3. This gives S.
According to the swap rule, if the hydrogen is not pointing down we switch it to R, but that would be wrong because if you use a molecular model kit and orient the structure, you have S.
Am I doing something wrong or is the Rule not a hard set rule and just correct >90% of the time?

Reply

James

The example I gave has H in the front. I didn’t cover an example where it is in the plane of the page.

This is a VERY old post. An even better trick I found was to do this: if H is in the plane of the page, do a single swap of H with whatever group is a dash. Then determine R/S. Whatever value you get will be the opposite of the true R/S. In your example, if you swap H with (dashed) CH3, and then determine R/S, it “looks like” R. But since we’ve done a single swap it’s the opposite of that – S – in accordance with what you say.

Relevant post:
http://www.masterorganicchemistry.com/2011/01/24/the-single-swap-rule/

Reply

Pavel S.

Great. Thank you!

I should have read the “single swap rule” more carefully. You’ve confirmed for me that the “R/S toggle” method above doesn’t work in all cases. The single swap rule makes sense and is more universal. Thanks again!

Reply

Leisa

Does the R/S Chart you made up there work all the time? I get the swap rule and whole idea behind it, but this chart makes life so much easier….

Reply

James

Leave a Comment