B.R.S.M. To strive, to seek, to find and not to give a yield


Top 5 Syntheses of August 2011

Okay, you know how this works by now - here, in no particular order, are my five favourite synthesis from August(ish). If I do this every month and this blog keeps going for a bit then this should be a useful resource for preparing problem sessions or just reminiscing. Also, I'd love to hear about good things I've missed!


Concise Total Synthesis and Stereochemical Revision of (+)-Naseseazines A and B: Regioselective Arylative Dimerization of Diketopiperazine Alkaloids

M. Movassaghi et al.J. Am. Chem. Soc, 2011, ASAP; [PDF][SI][GROUP]

DOI: 10.1021/ja206743v

Movassaghi seems to publish indole alkaloid syntheses at such a fantastic rate that it's easy to see them in the JACS ASAP and dismiss them as 'another Movassaghi paper'. We shouldn't, though, as I've never failed to learn something from reading one, and the amount of new reactions being generated is amazing. A recent cool example is the diazene based heterodimerisation of cyclotryptamines the group published last month, a new methodology designed to compliment their previously reported Co-mediated homodimerisation of similar compounds (seen, for example, in their excellent 2009 Science paper on the synthesis of (+)-11,11'-dideoxyverticillin A). Anyway, the new reaction in this paper, which allows rapid access to the two targets above, is a Friedel-Crafts-type arylation of various π-nucleophiles using C-3 halogenated hexahydropyrroloindoles as the electrophiles (activated with AgSbF6). Although this transformation was developed with the naseseazines in mind, an interesting discovery was made along the way. The group found that where poor C-6/C-7 selectivity was obtained in the arylation of indoles that the site of attack could be directed by the inclusion of a trifluoroborate substituent in the indole being arylated. This effect turned out to be quite general, and could be used to overturn the expected reactivity of a number of systems including anisole and thiophene. Overall, access to either naseseazine took only 9 steps, with excellent diastereoselectivity in the key C-C bond forming step.

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Top 5 Syntheses of July 2011

I'm going to try and make this a regular thing. Top 5 for May/June can be found here. Please stop by in the comments and point out any good ones I've missed (or rubbish the ones I've picked). As before, these aren't in any particular order, because that would be silly.

Total Synthesis of (-)-Histrionicotoxin

Fukuyama et al., Org. Lett., 2011, ASAP; [PDF] [SI] [GROUP]

DOI: 10.1021/ol2018032

Like the erythromycins from the previous post, the histrionicotoxin alkaloids have a rich and storied synthetic history (which you can get a flavour of in Rob Stockman's review in Nat. Prod. Rep., 2007, 24, 298-326). I'm often left a little unenthused by Fukuyama syntheses (a friend of mine described his tactics as 'the world war one approach to synthesis') but there's some interesting chemistry in this paper. The way in which chiral information is moved about the molecule is quite cool: asymmetry is first introduced by preparation of a chiral propargylic alcohol using the Noyori reduction, then transferred to a chiral silyl allene. This is then finally alkylated to generate an all carbon quaternary centre that allows a long sequence of reactions to be carried out under substrate control. There's also a retro-Brook rearrangement, an asymmetric propargylation and some dienyne metathesis to keep things interesting.

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Top Five Syntheses of May/June 2011

Here's an idea for a feature I've not seen anywhere else that I thought I'd try. It wasn't easy to choose, and my tastes in chemistry may be different to yours. These are not in any kind of order, because that would be silly. Please point out any nice work I've missed in the comments!

KCN's first dithiodiketopiperazine

Total Synthesis of Epicoccin G [PDF][SI][GROUP]

DOI: 10.1021/ja2032635

K. C. Nicolaou et al.J. Am. Chem. Soc., 2011, 133, 8150–8153

I was contemplating doing a full write up of this when I started blogging at the start of this month, but I'm not sure I'll get round to it now, unless it's a quiet few weeks or people really want to see one (let me know!). KC chooses a fantastically non-obvious disconnection for this molecule; the two g-hydroxycyclohexanones are actually derived from two molecules of tyrosine using a neat oxidative dearomatisation procedure developed by Wipf, followed by dimerisation. These spend most of the route masked as the 1,3-cyclohexadienes only to be revealed in the penultimate step by a [4 + 2] with singlet oxygen, followed by a Kornblum - DeLaMare rearrangement. How often do you see those?

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