Best practices in designing a synthetic route.

Question

Begin by asking two questions: Has the carbon count increases, decreased, or remained the same AND how has the functionality changed? Once you have answers to these two questions, look at the target compound (the product) and think about the ‘best’ way to generate that functionality. With responses to these three questions, you are most likely one step away from you solution!

Answer 1

The steps that you have outlined are a great way to begin to tackle a synthesis problem! I'm going to add some more details and a step-by-step approach to have a failsafe approach, however. This answer is a long read but gives a comprehensive guide and approach!

1. Look at the starting material(s) given and take note of the chemical formula (specifically the number of carbons) and any functional groups present. Examples of some common functional groups are alcohols, carbonyl groups, alkenes, alkynes, and alkyl halides among others.
2. For your functional groups, parse through a bit more. For example, if you have an alcohol, is it primary, secondary or tertiary? Is your carbonyl group an aldehyde, ketone, ester, etc? Take note of regiochemistry and stereochemistry where applicable. Be as descriptive here as possible as this prep work will limit the number of reactions you are selecting from when it comes time to put together your synthesis.
3. Follow step 1 again, but this time for your product.
4. Reread the question prompt to see what reagents and additional carbon sources you are allowed to use. Instructors handle synthesis problems differently, so you might not have much information to go off of here or you may have restrictions such as "using only carbon sources with 5 carbons or less" etc. Make sure you are clear on what you are and are not allowed to use in your synthesis.
5. Now you're ready to begin the retrosynthesis process. Retrosynthesis is the special term organic chemists use for designing a synthesis in the "reverse direction". You start from the product and find a precursor to the product (that is, a compound that it could have been made from).
6. Make sure that you have an organic reaction that would successfully make the product from your precursor before you get too far into your retrosynthesis! Use your prep-work from steps 1 and 2 to help you here. This is the trickiest part, but with enough practice you'll notice that you'll be able to correctly pick out the proper reaction for each step of your synthesis based on the functional group, carbon count, regiochemistry, and stereochemistry.
7. Repeat step 4 as many times a needed until your last "precursor" is in fact your starting material!
8. Make sure you use the special retrosynthesis arrow and that you're reading the synthesis backwards! It can be helpful to write the name of the reaction you're using in a specific step under the retrosynthesis arrow to keep all of your work organized.
9. As you work through your retrosynthesis, the precursors should begin to resemble the starting material more and more.
10. By step 6, you're almost done! Now you need to "translate" your retrosynthesis into the regular (or "forward") synthesis. Make sure you don't skip any of your steps here and that you are including full reaction conditions as needed! That means including relevant solvents, catalysts, and temperatures where needed. Don't forget to designate two-step one-flask or sequential reactions appropriately (a common example of hydroboration-oxidation)!
11. You're finally ready to check your work! Read through your synthesis from start to finish making sure that all of your structures are drawn correctly and that you have included all of your reagents and reaction conditions. Do one more quick check that you're not breaking any of the rules given in the question prompt.
12. I recommend trying to read the synthesis as if you weren't the one who wrote it (maybe pretend you're the professor grading it!) because we all make errors not accurately transcribing what's in our heads every once and a while!

Now remember to keep on practicing and that struggling through synthesis problems will help you master them! Good luck and have fun!