An explication of Fischer’s proof for the configuration of sugars is the capstone lecture in sophomore organic chemistry. However, like the “irrelevance” of the Diels Alder reaction that is frequently cited, some might say the Fischer Proof lacks value for the training of today’s students. To the contrary: there’s every reason to think old Fischer still has some magic yet in that beard of his. Here I lay out the argument for why it should be taught. The details of the proof itself are nicely presented here and here.
The Fischer Proof is complicated; carbohydrate structure and reactivity can be daunting. Sugar molecules have similar atoms and functional groups and primarily differ in their precise geometric arrangement. It simultaneously appears like everything is the same, and that there are too many details to keep track of. It takes time, effort, and a significant build-up of context for it to make sense. In general terms, that sounds like many of the world’s difficult problems that need to be solved. Rather than shy away from the topic, then, we should embrace it. If an effort is made to truly understand the proof, lessons that transcend organic chemistry can be found. The intellectual tools that derive from those lessons can then be applied elsewhere.
It wasn’t easy for Fischer either; consider the context for when he was working on this question at the end of the 19th century. The notion of tetrahedral carbon had been introduced and its relevance to stereochemistry was apparent, but the details were still murky. Observations on the composition and reactivity of carbohydrate compounds were not yet unified in any way. Consequently, Fischer was going off into the thicket of the unknown. Paraphrasing Lichtenthaler’s tribute  on the centennial of the Fischer Proof, “Textbooks give the false impression that chemistry as a discipline developed in an orderly way where discoveries followed one after the other in a logical progression. They imply that Fischer achieved his insights as a matter of historical course. They don’t detail the serendipity, the intellectual struggles of a dedicated researcher, nor the persistence that enabled him to succeed.” The tribute further pays homage to, “the creative processes underlying a fundamental discovery and the constructive logic that eventually led to it.”
The first lesson of the proof is that Fischer was able to vary his field of view back-and-forth from specific, detailed observations to general concepts that provided the framework to organize all of those observations. He cataloged the identity of his sugars based on their associations, generating a complex web of relationships.  The specific sugar starting materials as well as the reactions that transformed them were the variables in his investigation. Relationships between compounds were established through painstaking associations that arose from different combinations of starting materials and reaction sequences. Results accrued in a non-linear fashion; so, Fischer had to assemble disparate pieces of evidence into one unifying model that explained all the observations as a whole. He made sense out a large body of information by sweating the details while keeping the big picture in mind. The Fischer Proof is a master class in logical reasoning, a technique that is both valuable and generally applicable.
It is easy to take Fischer projections for granted. They consolidate information so efficiently that they fall victim to their inherent intuitiveness. Fischer’s second lesson, then, is the development of creative ways to organize information. The organizational system is clearly connected to the “field of view” lesson above. Fisher projections are proto-infographics; they put a physical manifestation on all the associations between the sugars he’d established. Because tetrahedral carbons could be asymmetric based on the groups attached to them (courtesy of van’t Hoff), Fischer knew there should be 16 isomers of aldohexose sugars. His initial paper on the configuration of sugars used van’t Hoff’s symbolism, where each asymmetric carbon was given a plus (+) or minus (-) sign to designate its configuration. This symbolism was helpful for indicating what the configurational possibilities of the aldohexoses were, but the rationale for implementing them broke down on molecules bigger than four or five carbons. After some thought and presumably a lot of fumbling with physical models, he came up with a 2D representation of those 3D tetrahedra; the Fischer projection was born. By working with the physical models, he was able to establish the relationships that he had observed in all those syntheses in the lab. He bridged a profound gap between physical observables and molecular structure. Model building is a creative activity essential new discoveries. That’s general.
Fischer was the first to admit that his hard work, planning, and reasoning were not everything. He conceded that, “a piece of good luck led me to the target.” The wisdom of Pasteur here fits perfectly. “In the field of observation, chance favors the prepared mind.” Fischer’s third and final lesson was that serendipity will reward attention to detail and tireless persistence.
 The format and ideas of this post were largely inspired by Lichtenthaler’s Angewandte review, Angew. Chem. Int. Ed. Engl. 1992, 31, 1541-1556.
 That’s just the beginning. Just think technical hurdles that Fischer had to overcome in his investigation, which added another layer of complexity to the endeavor.
* Thanks to William Bailey and Jeffrey Moore for reading a early draft of this post.