Piperonal + MEK -> Isosafrole?

[Rhodium]

What do you guys think of the Aldol-Grob reaction, where a benzaldehyde is condensed with a ketone under Lewis catalysis to yield phenyl-2-alkenes? Wouldn't this work nicely to make propenylbenzene from benzaldehyde and methyl ethyl ketone or even more interesting - isosafrole from piperonal?

It should be possible, as in In DOI:

10.1016/S0040-4020(01)89414-X

they use the reaction to synthesize a derivative of isosafrole, and in the articles below they prepare other phenylpropenes (Entry 13, Table 5, Ref 5), so I see no immediate obstacle to it. And who's the originator of this synthesis? Our old ally George W. Kabalka...


References:

[1]

Eur. J. Org. Chem. 1631-1634(2003)

(https://www.thevespiary.org/rhodium/Rhodium/pdf/phenyl-2-alkenes.aldol-grob-1.pdf)
[2]

Tetrahedron 54, 15525-15532 (1998)

(https://www.thevespiary.org/rhodium/Rhodium/pdf/phenyl-2-alkenes.aldol-grob-2.pdf)
[3]

J. Org. Chem. 63, 6438-6439 (1998)

(https://www.thevespiary.org/rhodium/Rhodium/pdf/phenyl-2-alkenes.aldol-grob-3.pdf)
[4]

Phytochemistry 39, 731 (1995)

(https://www.thevespiary.org/rhodium/Rhodium/pdf/phenyl-2-alkenes.aldol-grob-4.pdf)
[5]

J. Org. Chem. 64, 3157-3161 (1999)

(https://www.thevespiary.org/rhodium/Rhodium/pdf/phenyl-2-alkenes.aldol-grob-5.pdf)

[GC_MS]

Is this something similar?

A new direct synthesis of cinnamic acids from aromatic
aldehydes and aliphatic carboxylic acids in the presence of
sodium borohydride

Tetrahedron Letters 44 (2003) 3579-3580

(https://www.thevespiary.org/rhodium/Rhodium/pdf/benzaldehyde2cinnamate.nabh4-cat.pdf)

Abstract — Cinnamic acids have been prepared in 59–86% yields by a new direct synthesis from aromatic aldehydes and aliphatic carboxylic acids in the presence of sodium borohydride and N-methyl-2-pyrrolidinone (NMP) as solvent, at reflux (185–190°C), for 9–12 hours. Without sodium borohydride, this reaction is not possible.

DOI:

10.1016/S0040-4039(03)00529-X

I noticed the articles a handful of days ago and was interested in performing the reaction, just for the fun of synthesizing some cinnamic acids. Is the reaction mechanism identical?

[Rhodium]

Nope, the reaction you have linked to is a modification of the Perkin Reaction, but where the acetic anhydride usually required has been substituted with NaB(OAc)₄, formed in situ from NaBH₄ and excess acetic acid. Nonetheless, it is very interesting, as many bees have easier access to NaBH₄ than Ac₂O.

[Protium]

If I could just reflux piperonal and MEK with BF3 in hexane for 2.5 hours and walk out with 89% isosafrole.  That sure would handle some pesky aquisitions problems.  Hell, that would also be quicker than my isomerization workup, and save me all that time cleaning flasks.

Tee-hee

[El_Zorro]

Has the thought crossed anyone's mind that styrene is about common as dog shit?  Why styrene?  Because the CuO procedure gives you benzaldehyde cheap as fuck.  Now that you can get benzaldehyde by the kilo, and MEK is at the hardware store by the gallon, that's a shitload of propenylbenzene.  Just a thought.

[starlight]

are you sure that styrene --> benzaldehyde with CuO is that easy?

the patent for the CuO procedure works on a phenolic propenyl benzene in alkali solution.



I have had little success in attempts to oxidise isodillapiole with CuO. But then I've only had a couple of attempts.

[Hedonist_Rex]

I know bumping without a serious contribution is probably frowned upon in this forum, but this would be the holy grail after all....

Could a newbee aid this cause?

MEK is everywhere and cheap as dirt.

[El_Zorro]

MEK is everywhere and cheap as dirt.

Yeah, but piperonal isn't.

[Hedonist_Rex]

Fair enough, but some bees who might be tired of digging root bark may have access to a 500ml soxhlet and unwatched peppercorns by the kilo.

[El_Zorro]

I would think if you were going to invest in an unproven method, then you might look into using aniline hydrochloride to demethylate vanillin, then methylenate it to piperonal.

[El_Zorro]

So what all could a bee use as a Lewis acid?  AlCl₃ won't work for any methylenedioxy routes, but what else would work besides BF₃, or any of those other chems that a hobby bee can't get?

[Rhodium]

I think that is pretty much discussed in detail in the references I linked at the top. Have you read them all? There are well over a dozen catalysts mentioned, and they are all tried on different substrates, so that you can deduce which are compatible with what functionalities.