Still thinking of the In The Pipeline list and the Nazarov reaction (or cyclization) just stuck out at me since Derek and our Bayer team spent time in the indane world…….just think of the times you need a five-membered ring (D — you sure you haven’t done this reaction?). I will have to leave space for Pauson Khand I suppose.

Housekeeping for all of us who forgot:

Screen Shot 2013-11-21 at 6.51.04 AM

Classic Nazarov cyclization

There are so many variations to list from the classic approach to silicon-directed and tapping variations. These modern approaches have expanded the field from a great approach to cyclopete(a)nones to include stereoselective ideas from initial concept. But like everyone else, microwave has to get its pound of flesh. I have included a few schemes and references utilizing the method under microwave control in their research — to plant the seed.

Tetrahedron Letters 2006

Screen Shot 2013-11-21 at 6.58.52 AM

Conventional: TFA sealed tube 120C 4 h
Microwave: same temp: 20 min

Chemical Communications 2005 dienones heated in microwave — ILs really heat quickly — believe it!

Screen Shot 2013-11-21 at 7.05.55 AM

mw: DMA: 5 min ramp 180C, 30 min at temp
mw: IL: 1 min ramp to 250C, 2 min at temp

JOC 2006

Screen Shot 2013-11-21 at 7.18.56 AM

Friedel-Nazarov combination

BMCL 2009 (There are many examples in the literature combining a directed acylation to a keto ester for positioning an alkene for the Nazarov step)

Screen Shot 2013-11-21 at 7.21.54 AM

fused pyrroles

OK — I bet you can have a look through the literature as well. Look for some non-arene fused systems and some of the elegance of the Nazarov — lots of cool approaches out there.

Advertisements