Frontier, He, Huang and Sun. JACS, 2006, ASAP. DOI: 10.1021/ja068150i.
Well, I’m back. Not quite up to speed – there’s been loads of totally synthetic action over the last three weeks, but I’m working my way through the journals, and posting as I go. As an aside, I’d like to thank everyone at Oxford for their welcome, kindness and support – moving labs isn’t easy or fun, but they’ve been great (especially the Fleet group :))
On with the synthesis! I’m starting with a great JACS article, posted at the close of last year by Alison Frontier at Rochester. Merrilactone has been a popular target, with syntheses by Danishefsky, Mehta and Inoue. Frontier’s approach was to use the incredibly funky Nazarov Cyclisation to build the central C ring, and then use a radical cyclisation to complete the B ring. The implementation was sweet:
Although by no means convergent, this path allowed them to build up molecular complexity at an astonishing rate. Completion of the target took around nine steps, again in a linear fashion, and using more routine chemistry, but their judicious use of conditions allowed substrate directed additions and reductions, generating some useful distereomeric control.