Determining R/S Nomenclature at a Glance in Three Easy

Steps
Note: With this method you never have to switch groups to see what the
stereochemistry is. Using the "drive-the-car" analogy, what we are doing
here is defining the steering wheel in relation to the steering column
(which is normally behind the steering wheel):
1. Determine the priorities of the four attached groups from highest (1) to lowest (4).
This is the same as in all methods.
2. Draw the steering
wheel. Draw a curved
arrow around from 1 to 2
to 3 and back to 1 and
note which direction this
arrow goes, clockwise
(cw) or counterclockwise
(ccw).
The distinct feature of
this method is that you
make a full circle, from
1 to 2 to 3 to 1,
completely ignoring the
lowest priority group.
3a. If the lowest priority group is behind the steering wheel, then this is the standard orientation:
clockwise is R and counter-clockwise is S. (Turning the steering wheel clockwise turns the car to
the right--R.)
Note that Fischer projections are best depicted as bow ties with horizontal groups coming out
and vertical groups going back from the central carbon atom.
3b. If the lowest priority group is in front of this curved arrow, then the assignment is reversed:
clockwise is S and counterclockwise is R. (Basically, you are looking at the steering wheel from
the perspective of the engine compartment!)




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

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,
youre 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
youre 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 were looking in mirrors. If Im 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. Its the same thing with molecules.

This trick seems obvious, but Ive met enough people who dont 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 brains
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. ]

The Single Swap Rule
I dont think there are that many tricks to doing well in organic chemistry, but there are a few.
I was kind of surprised last month when I talked to a number of students who hadnt ever come
across todays trick, which is probably the most useful of them all. I used to call it the R/S
toggle but a much better name for it comes from Steven, who calls it the Single Swap Rule.
Heres how it works. Take a molecule with a stereocenter, like (S)-2-butanol (drawn below). If
you swap ANY TWO substituents, you will invert the configuration of the stereocenter.
That is, switching any two substituents will give you (R)-2-butanol.
There are six possible ways you could do this, and theyre all depicted below.
By the way, dont take my word for it if you cant see this, demonstrate to yourself that each of
these six molecules is (R)-2-butanol .

The Single Swap Rule comes in handy for two situations in particular.
1. Determining whether a stereocenter is (R) or (S)
2. When you need to draw the enantiomer of a stereocenter like when you are drawing the
product of an SN2 reaction for instance.
The first order of business in determining whether a stereocenter is (R) or (S) is to number the
priority of the substituents according to their priorities. Im not going to talk about how to do this
today, although there are plenty of great resources on how to do so if youd like to practice this
essential skill. According to the rules, once youve ordered the substituents, you need to put the
4th ranked substituent in the back and then determine whether the 1st, 2nd, and 3rd ranked
substituents trace a clockwise or counterclockwise path. In practice, few people follow this to

the letter. Thats because you still get the same result if the 4th ranked substituent is connected to
a dashed bond.

The upshot of this is that determining (R)/(S) is fairly straightforward as long as the 4th ranked
substituent is dashed. But what if your examiner unhelpfully draws the 4th ranked substituent as
a wedge, or even off to one side?
Thats where the Single Swap rule comes in handy.
Lets say were given this molecule. Note that priority #4 is pointing out in front. Instead of
redrawing the whole molecule to depict it such that #4 is in the back, we can now bust out this
trick. Switch the #4 substituent with whatever is in the back. Since were doing a single swap,
were going to *invert* the stereochemistry from (R) to (S) or vice versa. Now since the #4 is in
the back, we can easily determine (R)/(S) and here, its (R). Since we did a single swap, that
means that our original stereocenter must have been (S).
What if #4 is pointing off to the side? Same thing. Swap it with whatevers in the back. This will
invert the stereochemistry. So again, when we determine (R)/(S), we remember that our
original stereocenter will be the opposite.

Drawing the enantiomeric configuration at a stereocenter.
The Single Swap Rule also comes in handy when you need to show that a stereocenter has gone
through inversion of configuration. If youve studied the SN2 reaction, you know that due to the
backside attack, this reaction proceeds with inversion. But Ive seen lots of students get confused
when it comes time to actually draw the products. The single-swap rule makes it easier. Heres
an example of what not to do and also a way to systematically apply the Single Swap rule in
order to be able to reliably draw inversion of configuration.

Do this; 1) draw your starting material. 2) do a single swap. this will invert the stereocenter. 3)
replace your leaving group with your nucleophile. Thats it. Youve now shown an SN2 with
inversion of configuration.
The Single Swap also works for Fischer projections, Newmans, you name it this is why, I
hasten to note, you arent allowed to flip any two atoms on a Fischer you end up getting the
opposite configuration.

With practice youll end up doing this in your head just figure out the priorities, trace the path
of 1,2, and 3, and if #4 is in the front or on the side, remember that its the opposite of whatever
you get (because #4 is in the front). Its probably the most useful trick there is in Org 1, and I
still use it almost every single day.