Handling nitrogen

Here is a great sequence to (-)-lepistine that has been developed by Professor Fukuyama and his students at the University of Tokyo. For many years, Fukuyama has been popularizing the use of the nosyl group. This chemistry has turned into one of the most useful ways to handle nitrogen in complex molecule synthesis. I forgot who told this to me, but common wisdom of synthesis tells us that adding one nitrogen atom to a molecule adds approximately one extra year to a student’s PhD. Just for clarity: I refer to a comparison between two molecules, one of which is one N atom “richer”. I have to admit that there is probably some truth to this statement (students from my lab: please ignore this sentence – otherwise we might be in trouble). Anyways… Back to Professor Fukuyama: the nosyl group is a fabulous way of handling nitrogen in synthesis. In the (-)-lepistine constuction, you see a great demonstration of clipping nosyl groups off, which generates an iminium ion in the same pot. After that, a lovely transannular collapse takes place, leading to the formation of the core of the natural product. Also noteworthy is the bridgehead double bond in the intermediate. All those things that are not supposed to happen in the second year organic chemistry I just taught two months or so ago!

rr

http://pubs.acs.org/doi/pdfplus/10.1021/ol5010033

2 thoughts on “Handling nitrogen

  1. sorry for nitpicking, I think the used nosyl protecting (or leaving) group is actually the ortho isomer – please see the supporting info. If I remember correctly there is a considerable difference in the ease of removal of ortho vs para nitrosulfonyl.

Leave a Reply

Fill in your details below or click an icon to log in:

WordPress.com Logo

You are commenting using your WordPress.com account. Log Out / Change )

Twitter picture

You are commenting using your Twitter account. Log Out / Change )

Facebook photo

You are commenting using your Facebook account. Log Out / Change )

Google+ photo

You are commenting using your Google+ account. Log Out / Change )

Connecting to %s