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Chemistry Forums for Students => Organic Chemistry Forum => Topic started by: wallysheng on July 13, 2009, 12:05:03 AM

Title: synthesis 6,6-Difluoro-bicyclo[3.1.0]hexane-3-carbaldehyde 494210-62-7
Post by: wallysheng on July 13, 2009, 12:05:03 AM

Hi All,

Recently we started a new project with a need of 6,6-Difluoro-bicyclo[3.1.0]hexane-3-carbaldehyde (CAS494210-62-7). Has anybody done this compound before? Any opinion on this case? We appreciate if someone can provide relative info or paper. Thanks!    :)

Wally

Title: Re: synthesis 6,6-Difluoro-bicyclo[3.1.0]hexane-3-carbaldehyde 494210-62-7
Post by: sjb on July 13, 2009, 03:32:11 PM

Cis or trans?

Assuming I've converted name to structure correctly, how about RCM on diallyl malonate, then Krapcho monodecarboxylation, addition of difluorocarbene to the double bond, then reduction of the acid to the aldehyde?

Title: Re: synthesis 6,6-Difluoro-bicyclo[3.1.0]hexane-3-carbaldehyde 494210-62-7
Post by: wallysheng on July 14, 2009, 12:08:49 AM

It seems ok but if so we need to start this case from scratch. We appreciate your opinion. Thank you very much!

Title: Re: synthesis 6,6-Difluoro-bicyclo[3.1.0]hexane-3-carbaldehyde 494210-62-7
Post by: sjb on July 14, 2009, 03:32:09 PM

I'm not saying that's the *only* way to make it - what are your thoughts?

Title: Re: synthesis 6,6-Difluoro-bicyclo[3.1.0]hexane-3-carbaldehyde 494210-62-7
Post by: wallysheng on July 15, 2009, 12:44:26 AM

Thanks!
But we'd like to know a relative mature route for this synthesis. Using the starting material you mentioned above we don't know how to monitor the reaction. It hard to monitor the progress of the reaction. Have you done familar case before?

Title: Re: synthesis 6,6-Difluoro-bicyclo[3.1.0]hexane-3-carbaldehyde 494210-62-7
Post by: sjb on July 15, 2009, 02:13:14 AM

Well, the first step I mentioned above has decent precedent, in e.g. http://dx.doi.org/10.1021/jo030005p  (3  :rarrow: 4), and is used as a model reaction for the activity of RCM in general, from what I can see. For the decarboxylation, perhaps http://dx.doi.org/10.1016/S0040-4039(00)90519-7 is the original report. Reduction has too many references to list. Carbene addition - perhaps http://dx.doi.org/10.1039/b212232d ?

As to monitoring, I appreciate that the reactants don't really have chromophores, but depending on your set-up, I guess staining TLCs, or NMR or ... ?

What were you planning on using as a starting material and your route?

Title: Re: synthesis 6,6-Difluoro-bicyclo[3.1.0]hexane-3-carbaldehyde 494210-62-7
Post by: kiwi on July 15, 2009, 02:31:40 AM

If cost is an issue, both sodium trifluoroacetate and sodium chlorodifluoroacetate are cheaper sources of :CF2, as they both fragment on heating:

X-CF2-CO2Na -> :CF2 + NaX + CO2

I imagine you're going to need to use modern chemistry techniques (TLC or HPLC, NMR etc) to monitor the reaction no matter which route you choose. 

Title: Re: synthesis 6,6-Difluoro-bicyclo[3.1.0]hexane-3-carbaldehyde 494210-62-7
Post by: sjb on July 15, 2009, 01:59:10 PM

Quote from: kiwi on July 15, 2009, 02:31:40 AM

If cost is an issue, both sodium trifluoroacetate and sodium chlorodifluoroacetate are cheaper sources of :CF2, as they both fragment on heating:

X-CF2-CO2Na -> :CF2 + NaX + CO2

True, I'm sure there are easier / cheaper methods out there, I was just going on a quick use of a FWSE, as I'm very limited in what literature I can easily access.

Title: Re: synthesis 6,6-Difluoro-bicyclo[3.1.0]hexane-3-carbaldehyde 494210-62-7
Post by: wallysheng on July 17, 2009, 04:11:51 AM

We have not fixed the route yet? We are discussing and considering your methods. Thanks!!!