Realino’s CHE 232 Archived Resources

Tips

It may seem that each synthesis problem is unrelated to any other, but there are in fact common motifs and techniques that elicit transformations in manifold ways. If these are identified early, they can provide invaluable clues to an elegant (and efficient) synthetic route.

Below is some general advice on approaching synthesis problems.

  1. Find some obvious forward steps that may get you closer to the product. Usually this is most effective for simpler problems (3 steps or less), but you are required to provide the forwards and backwards route nonetheless so this is a solid first step.
  2. Make a list of transformations. The most immediate is the lengthening or shortening of the carbon backbone. In the case of lengthening, we know that substitution with an acetylide anion is useful for extending the carbon framework. Recently, we learned some reactions that can shorten a backbone (e.g. ozonolysis).
  3. Notice the movements of particular functional groups. For instance, if an alkene has shifted over by one carbon, you could try adding a leaving group and subsequently eliminating, which may produce an alkene in a new location. Alternatively you could try other addition or radical reactions to the newly formed alkene. Also, DO NOT forget about carbocation shifts! Anytime you form a secondary carbocation, look for possible methyl or hydride shifts.
  4. If a synthesis seems impossible, i.e. the target wildly differs from the starting material, be creative! (You would never encounter an “impossible” problem, anyway). Some things to consider are:
  • ring expansion or contraction (often by methyl shifts).
  • carbocation shifts.
  • thermodynamic vs. kinetic products (e.g. 1,2- vs. 1,4-additions to dienes).
  • cyclization/annulation (Williamson ether synthesis is common. Others include Diels-Alder and Robinson annulation).

 

Just in case the material in class isn’t exciting enough, here are some nice pictures of reactions from the friendly chemist at labphoto.tumblr.com

This reduction using borane (as in hydroboration-oxidation) is interesting in that it generated borane in situ, i.e. in the reaction flask.
This reduction using borane (as in hydroboration-oxidation) is interesting in that it generated borane in situ, i.e. in the reaction flask.

 

Here’s a chemical we know and love! N-bromosuccinimide places a bromine atom at the allylic carbon. The lovely color here is possibly due to termination to elemental bromine.

Here's a chemical we know and love! N-bromosuccinimide places a bromine atom at the allylic carbon. The lovely color here is possibly due to termination to elemental bromine.
This was a reduction using hydrogen and palladium on carbon. The black color here is due to the Pd-C complex.
This was a reduction using hydrogen and palladium on carbon. The black color here is due to the Pd-C complex.
This was a reduction using hydrogen and palladium on carbon. The black color here is due to the Pd-C complex.