van Maarseveen, Hiemstra, Wanner, Boots, Eradus and de Gelder. Org. Lett., 2009, ASAP. DOI: 10.1021/ol900888e.
Okay, jsut a little Org. Lett. to get my hand back into this blogging thing after being on holiday for a week. The writing conditions have changed a little in Tot Syn towers, too – I’m now typing this on a new keyboard – a lovely aluminium Apple thing. So I bid my old Microsoft ‘Natural’ keyboard goodbye, after six years of faithful service, and also six years of crud (putting it as delicately as possible) under the keys. And a thesis too. So this is the first real test for the new ‘board, so lets see how it does.
This paper from Holland is definitely a methodology paper with a bit of total-synthesis to prove the point… and looking back into the past, the methodology was proved last year. The key is an organocatalytic asymmetric Pictet?Spengler reaction – a useful approach, and one that has been developed by other groups (see reference two). Using an elaborated BINOL-phosphoric acid catalyst, in rather low loading, they were able to develop a rather useful yield and enantiomeric excess. By reducing the planiarity of the naphthalene moieties, the e.e. could be further enhanced, with the price being a more exotic catalyst. I’m not entirely sure which one they ran with, but I’m fairly sure it was catalyst B, as they were able to run the reaction on a 5 mmol scale.
With the vast majority of the compound complete, they group were left with only one more C-C bond forming reaction to complete. This vinyl iodide-enolate coupling was lifted from some work by Sole and Bonjoch back in 2004 (it’s in Adv. Synth. Catal. – not a journal I read enough… never enough time!), and works reasonably well in this case. This is a situation where, whilst the yield was moderate, the result meant that they had their synthesis complete in only five steps (from known precursors).1 With only a deprotection remaining, this is a good job well done – proving the utility of their method nicely. I look forward to seeing it used by other groups in the near future!
 Why am I bothered about this? Well, one of the tendancies I see more often these days (probably cause I’m looking for it) is for PIs to only publish in JACS or ACIEE (or better), meaning that only the best chemistry gets published. This means that the (mearly) very good chemistry (you know what I mean – 80ish% yields, or 4:1 d.r., et c.) gets left on the bench, and no-one wins. Grrr. Any contrary views? (Sure, I know it’s nice for PIs to have that lovely list of publications, where it’s only those top-rung journals. But surely there’s space for other journals in there…)