In the Classroom
A Simple Method of Drawing Stereoisomers from Complicated Symmetrical Structures A. Haudrechy Laboratoire de Synthèse des Substances Naturelles, Université Paris Sud, 91405 Orsay cedex, France;
[email protected] When considering molecular structures presenting a high degree of symmetry, it is sometimes nontrivial to draw all possible stereoisomers and to identify their relationships (enantiomers, diastereoisomers, or identical structures). In this article, a systematic, rapid mnemonic procedure is presented to aid in visualization of complex cases. Let’s start with two simple cases, such as allenes 1a and 1b (1) and atropoisomers 2a and 2b (2). A “Newman-like” projection significantly helps the students to visualize the molecules and to show those that are chiral. Looking at one edge of the above molecules gives the projections of 1a, 1b, 2a, and 2b. The front line (bold line) corresponds to the first plane and the back line to the second one:
H
C
C
C
Cl
Cl
H 1a Cl
Cl
H C
Cl
H H
1a
Cl
Cl
Cl
Cl
C
C
H
S
OH
HO HO H
* R
* HO 3
*
H 3a
Looking at one edge of the above molecule gives a Newman-like projection of 3a. The front line (bold) corresponds to the first cyclopentane; the back line, to the second one. This representation can be further simplified by using a hybrid Newman/Cahn–Ingold–Prelog picture (3), in which the stereogenic centers are symbolized by stars and finally replaced by the usual notation R or S (Cahn–Ingold–Prelog):
Cl
Cl H
1b
a systematic approach beginning with the study of one of the possible stereoisomers, for example 3a (note that there are three stereogenic centers, designated by asterisks, so there should be a maximum of eight possible stereoisomers):
HO
*
Cl 1b
HO2C CO2H
CO2H CO2H
O2N NO2 O2N
NO2
3a
Let us now consider the eight possible stereochemical representations 3a to 3h. By convention, we propose to place the stereogenic center on the front-line, at the top of the drawing: S R
HO2C NO2
CO2H HO2C
CO2H O2N
The mirror image of 1a is clearly 1b:
1a
3c
3d
R
R
R
R
R
Cl
HO2C
2a
3a
NO2
(Mirror)
3h
2b
Let’s follow now with more complicated examples. Careful analysis of structure 3 can lead to a correct determination of the number of stereoisomers; however, we propose
R
R Horizontal Flip
Rotation 90°
S 3f
Following the same spatial manipulations, we can see that 3c = 3h: S
S
NO2
NO2
3g
S R
CO2H
CO2H
S
3f
S
1b (Mirror)
CO2H O2N
R
S
By a horizontal flip of 3a, followed by a rotation of 90°, we obtain 3f (please note that a rotation or a flip does not change any configuration):
and the mirror image of 2a is clearly 2b:
864
3b
3e
Cl Cl
S S
3a
2b
Cl
S R
S
NO2 NO2
2b
R
3a
S
2a
2a
S
OH * H
*
H
H
R
R R
3c
Horizontal Flip
S Rotation 90°
3h
The relationships between the six remaining stereoisomers can be found by considering the mirror images (note
Journal of Chemical Education • Vol. 77 No. 7 July 2000 • JChemEd.chem.wisc.edu
In the Classroom
that the mirror image of the configuration R is S): S
S
R R
R
S
3a = 3f
S 3h = 3c
3g
R
S R
3e
Clearly, the enantiomers of 3a, 3b, and 3d are respectively 3h (= 3c), 3g, and 3e. To conclude, structure 3 has three possible pairs of enantiomers. All other relationships are diastereoisomeric. Let’s demonstrate another case with a more complex molecule. This powerful method gives an easy solution to the same kind of stereochemical problem when applied to structure 4, having possibly 5 stereogenic centers (designated by asterisks). One of the possible stereoisomers, for example 4a (4), is drawn as follows: R
*
+ N *
Me Me
*
4
S
S Horizontal Flip
4c
+ N
Me
S
S R
4g
R
R R
4a
R S
R R
4e
S S
R S
4i
R S
4m
R S
R
4n
S
4d
R R
S R
4g
4b
R R
4o = 4c
S R
R
4l
R
4o
R
S S
S S
4f
R S
S S
4k
S
4k
Clearly, the enantiomers of 4a, 4b, and 4f are respectively 4m (= 4d), 4o (= 4c), and 4k. The mirror image of 4g is 4j (= 4g…), meaning that this stereoisomer is the only achiral one, possessing S4 symmetry:
4h
S
S S
S S
(Mirror) S
R
4c
R R
4j
4m = 4d
S
S
S S
4j
R R
S
S
S
(Mirror)
S R
R
R S
R R
S R
4f
S R
S
S
4i
R
R
R R
R
S
S
S R
4b
R R
R
S
R S
Rotation 90°
(Mirror)
S R
R
4a
R
R
S
R
R
R
We will now consider the 16 possible stereochemical representations 4a to 4p:
S
S
R
R
S
Rotation 90°
S
S
R
4e
Thus, we can deduce that structure 4 possesses seven stereoisomers (4a, 4b, 4c, 4d, 4f, 4g, and 4k). Relationships among the seven remaining stereoisomers can be found by considering drawings of the mirror images:
4a
S
R
S Horizontal Flip
S S
R
R
H
4a
R
S S
R
S
Me
S
and that 4g = 4j:
S H
H H
R
Rotation 90°
S S
(Mirror)
*
4b
R
S
S
*
R Horizontal Flip
R
Following the same spatial manipulations, we can see that 4c = 4i:
R
3d
R R
(Mirror) S
R
R
3b
(Mirror)
S
S
4p
By a 180° rotation in plane, we can show that 4a = 4p, 4b = 4n, 4c = 4o, 4d = 4m, 4e = 4h, and 4i = 4l. By a horizontal flip of 4b followed by a rotation of 90°, we found that 4b is identical to 4e:
S S
R
R
R S
4g
4j
(Mirror)
To conclude, structure 4 possesses three pairs of enantiomers and one achiral stereoisomer. All other relationships are diastereoisomeric. In summary, we believe that this educational method will be helpful for a number of other complicated structures, allowing a savings of time when teaching stereochemistry. Testing this method for six years (approximately 30 students every year) has saved us at least 30 minutes in a 2-hour class and greatly facilitates the comprehension of stereochemistry.
JChemEd.chem.wisc.edu • Vol. 77 No. 7 July 2000 • Journal of Chemical Education
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In the Classroom
Acknowledgment Deep thanks to Marc Gingras for helpful discussions. Literature Cited 1. Runge, W. In The Chemistry of Allenes; Landor, S. R., Ed.; Academic: New York; 1982; Vol. 3, pp 579–678. Runge, W. In The Chemistry of Ketenes, Allenes and Related Compounds; Patai, S., Ed.; Wiley: New York; 1980; Part 1, pp 99–154.
866
Rossi, R.; Diversi, P. Synthesis 1973, 25–36. 2. Oki, M. Top. Stereochem. 1983, 14, 1–81. 3. Cahn, R. S.; Ingold, C.; Prelog, V. Angew. Chem., Int. Ed. Engl. 1966, 5, 385–415. Cahn, R. S. J. Chem. Educ. 1964, 41, 116. Fernelius, W. C.; Loening, K.; Adams, R. M. J. Chem. Educ. 1974, 51, 735. Prelog, V.; Helmchen, G. Angew. Chem., Int. Ed. Engl. 1982, 21, 567–583. 4. McCasland, G. E.; Proskow, S. J. Am. Chem. Soc. 1955, 77, 4688.
Journal of Chemical Education • Vol. 77 No. 7 July 2000 • JChemEd.chem.wisc.edu
