Paucity of TMS-CN, lack of preparative chiral HPLC and a passion for enantioselective synthesis has led me to consider an alternative route to the alcohol side chain required for the chiral ether compounds (e.g. MMV670652).
Based on PhD work that I did with Aurélien Bigot and Matthew J Gaunt, I'm working on an catalytic enantioselective route to this side chain. Based on (http://pubs.acs.org/doi/abs/10.1021/ja206047h) and the route below:
Synthesis of Iodonium Salt:
Synthesis of (3,4-difluorophenyl)(mesityl)iodonium triflate (AEW 128-1)(http://malaria.ourexperiment.org/uri/54c)
Synthesis of N-acyl-oxazolidinone:
Synthesis of 3-(2-(Benzyloxy)acetyl)oxazolidin-2-one (AEW 129-1)(http://malaria.ourexperiment.org/uri/558)
Lovely chemistry. Freon gas?
yeah...no Freon! Scheme is copied and pasted from the earlier CRO route. We may not introduce CHF2 anymore but focus on other more synthetically accessible ethers instead.