When we learn the fundamentals of organic chemistry, we tend to receive trivialized material where many details are omitted for clarity. I think this is not only essential, but is also critical to the establishment of a solid chemistry foundation. The trouble is that we leave our students in the dark when it comes to gaps. I suppose graduate school is expected to take care of those gaps… Let’s look at Sn2 chemistry at sp2 centers. This should not work, yet Professor Narasaka has spent a good portion of his career perfecting these kinds of reactions. Below is a reference to a review he has written and an example of a well-known Sn2 substitution at a hydroxylamine nitrogen center. The fact that the syn-form does not lead to any product formation supports the feasibility of backside attack (and so do many other detailed mechanistic studies). Another example I include comes from Merck and shows an awesome and scalable way to make pyrrolidines. This high-yielding process employs an alkyl halide, which is a “no-no” when we teach undergraduate chemistry. This is due to overalkylation nightmares (“since this cannot work, let me tell you about the Gabriel synthesis…”). By the way, if you take a look at the reference, you will note that this chemistry works on a multi-kilogram scale and delivers fantastic yields. You can also use similar reactions to make piperidines and morpholines, the cornerstones of drug discovery.

http://onlinelibrary.wiley.com/doi/10.1002/ejoc.200500389/abstract

http://pubs.acs.org/doi/abs/10.1021/jo981170l