3-Cyano-3-desoxy-10-ketomorphinans

[pHarmacist]

Microwave-Promoted Pd-Catalyzed Cyanation of Aryl Triflates: A Fast and Versatile Access to 3-Cyano-3-desoxy-10-ketomorphinans



Ao Zhang and John L. Neumeyer

Org. Lett.; (Communication); 2003; 5(2); 201-203.  DOI:

10.1021/ol027256p

Abstract: A methodology for the microwave-promoted conversion of triflates to the corresponding nitriles by using 8% equiv of Pd(Ph3P)4 as the catalyst and 2.0 equiv of Zn(CN)2 as the cyanide source has been developed. This method is highly efficient for the preparation of 3-cyano-3-desoxy-10-ketomorphinans. The reaction was generally completed in 15 min at 200 C and produced products in greater than 86% yields.
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Full-text:

http://pharmacist8.tripod.com/cyanoketomorph.pdf

[Rhodium]

Nice article, pH!

For people who don't know how to find the Supplemental material to the article above, here's the

Experimental Section.

(http://pubs.acs.org/subscribe/journals/orlef7/suppinfo/ol027256p/ol027256psi20021205_020936.pdf)

Have you checked the references to the pharmacological evaluation of the opioid agonists mentioned in the articles, or were you just interested in the article because of the possibilities which opens with this novel Phenol Aryl Triflate Aryl Cyanide (Benzonitrile) transformation?

Myself, I would be highly interested in hearing about someone using this procedure to make 2C-CN or similar, it is likely that the procedure can be applied to iodides and bromides too.

[Kinetic]

I stumbled across this similar reaction at OrgSyn. Again it involves Pd-catalysed nucleophilic aromatic substitution on an aryl triflate, this time by an alkylthiol. The substitution even works when there is an electron donating group para to the -OTf leaving group (and it's microwave free ).

The full article is at

http://www.orgsyn.org/orgsyn/prep.asp?prep=v79p0043

 
It'd be great if it could be applied to more heavily substituted aromatics; and if it worked on halides, it'd be an excellent one-step from 2C-X to 2C-T-anything you can think of. It could also be a nice way to 3,1-benzoxathiole-6-yl carboxaldehyde - the 4-thio analogue of piperonal, via the triflate ester of vanillin, followed by dealkylation and methylenation.