A Retrosynthetic Analogy Anne's Sauteed Summer Squash lwln J. Levy Gordon College. Wenham, MA 01984 Retrosynthetic analysis is a problem-solving methodology that can he used to plan the synthesis of complex organic products (target molecules) using simpler organic reagents as startina materials. This topic is esoeciall~important in the student's intellectual gro&h since'it challenges the student to develop intuiti\.e reasoning. The importance of this technique is e;idenced by the more prominent inclusion of retrosynthetic examples in many of the recently released organic chemistry textbooks.' For many students of organic chemistry, the concept of retrosynthetic analysis represents a major departure from the problem-solving techniques with which they are most familiar. Accordingly, students often experience great difficulty utilizing the method. This is particularly true since the mastery of reactions in the forward direction is still the primary concern of most students a t this stage. The added burden of mentally visualizing the reactions in reverse obscures the development of the problem-solving technique. I have found that the principle of retrosynthesis is best introduced using examples outside the realm of organic chemistry. In particular, I relate to my class the fact that one of my favorite vegetable dishes is Anne's Sauteed Summer Squash. This simple but delightful dish is made with (preferablv freshlv. nicked) summer souash and onions which are . sauteed in hutter with a generous.application of pepper. The class is then presented with the foll~~wing problem: Consider a farmer who has an adequate supply of cooking utensils and common spices. How could the farmer insure that he can enjoy sauteed summer squash? The class enjoys the nontechnical nature of the problem and quickly supply the following analysis: Sauteed summer squash CAN BE OBTAINED FROM Summer squash, Onions, Butter, Common Spices Using thedisconnec~ionsymbol( - j , which is read'kan he obtained from", we can write the first-order solution as: Sauteed summer squash
-
Summer Squash/Onions/B~tter/Spices
Since spices are already available (as are inorganic reagents and common solvents t o the student solving synthesis problems) we need only concern ourselves with the first three items. The students will readily obtain the following conversions: Summer squash Summer squash seeds Onion Onion sets
--
Thus, the problem is reduced to simple starting materials
that are readily available to the farmer.The butter, however, is a somewhat more complicated matter. The farmer knows that: Butter
- Cream
Raw Milk
and, of course, that: Raw Milk =+ Cow In summary, our farmer must obtain a supply of squash seeds, onion sets and maintain a dairy cow in order to he assured the availability of sauteed summer squash. This analvsis is useful in that the student is constantly reminded t i a t each retrosynthetic step is impossible to actiallvrealize: rather. each step charts the course to the eventual forward' pathway. In other words, no chef can convert sauteed summer squash into separate piles of squash, onions, butter, and pepper. The conversion of butter into a cow is equally problematic. Furthermore, the retrosynthetic pathway is not sufficient to allow a novice farmerlchef to prepare the desired dish. Our completed "retrorecipe":
Pepper
-
Raw Milk
-
Cow
must be supplemented by a valid set of instructions for the actual preparation: Caw
ck%
(11 SeparsB
Cow Milk (2, Churn t Butter
( 1 ) Plant
Squash seed (zjcu,ivakt Summer Squash 'Ii%
"A"
*""":,
"B" pepper
After solving this problem, a simple synthetic example completes the analogy. Students readily accept the reverse reaction pathways as convenient maps allowing an eventual synthetic route to be plotted.
' Solomons,T. W. G. Organic Chemistry, 4th ed.; Wiley: New York,
1988;pp 333-338. Vollhard, K. P. C. Organic Chemisw Freeman: New York, 1987; pp 293-295. Wade, L. G.,Jr. Organic Chemistry: Prentice-Hall: Englewood Cliffs, NJ. 1987;pp 231-233.Carey, F. A. Organic Chemistry; McGraw-Hill: New York, 1987; pp 533-536.
McMurry. J. Organic Chemistry, 2nd ed.; .:rooks/Cole: Pacific Grove, CA. 1988;pp 557-559.
Volume 65 Number 10 October 1988
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