[wallysheng]

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

[sjb]

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?

[wallysheng]

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

[sjb]

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

[wallysheng]

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?

[sjb]

Well, the first step I mentioned above has decent precedent, in e.g. http://dx.doi.org/10.1021/jo030005p  (3  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?

[kiwi]

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. 

[sjb]

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.

[wallysheng]

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